Trial Outcomes & Findings for A Study of Abemaciclib (LY2835219) in Combination With Other Anti-Cancer Treatments in Children and Young Adult Participants With Solid Tumors, Including Neuroblastoma (NCT NCT04238819)

NCT ID: NCT04238819

Last Updated: 2025-10-07

Results Overview

The RP2D of abemaciclib was determined based on the totality of safety, tolerability, and pharmacokinetic results. RP2D of abemaciclib in combination with 50 mg/m²/day irinotecan and 100 mg/m²/day temozolomide on days 1-5 of 21-day cycles was reported.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 47 participants
• Primary outcome timeframe: Cycles 1 and 2 (21 Day Cycles)
• Results posted on: 2025-10-07

Participant Flow

Participant milestones

Measure	Part A Cohort A1 Participants received: * Abemaciclib: 70 milligrams per meters squared (mg/m²), administered orally twice daily (BID). * Irinotecan: 50 mg/m²/day, administered intravenously (IV) on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1 Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part C Cohort C1 Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. * Dinutuximab: 17.5mg/m²/day, administered IV on Days 2-5 of each cycle. * Granulocyte-macrophage colony-stimulating factor (GM-CSF): 250 μg/m²/day, administered subcutaneously (SC) on Days 6-12 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
Overall Study STARTED	7	13	3	9	3	11	1
Overall Study Received At Least One Dose of Study Drug	7	13	3	9	3	11	1
Overall Study COMPLETED	7	13	3	8	2	7	0
Overall Study NOT COMPLETED	0	0	0	1	1	4	1

Reasons for withdrawal

Measure	Part A Cohort A1 Participants received: * Abemaciclib: 70 milligrams per meters squared (mg/m²), administered orally twice daily (BID). * Irinotecan: 50 mg/m²/day, administered intravenously (IV) on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1 Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part C Cohort C1 Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. * Dinutuximab: 17.5mg/m²/day, administered IV on Days 2-5 of each cycle. * Granulocyte-macrophage colony-stimulating factor (GM-CSF): 250 μg/m²/day, administered subcutaneously (SC) on Days 6-12 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
Overall Study Ongoing Treatment	0	0	0	0	1	4	0
Overall Study Withdrawal by Parent/Subject	0	0	0	1	0	0	1

Baseline Characteristics

A Study of Abemaciclib (LY2835219) in Combination With Other Anti-Cancer Treatments in Children and Young Adult Participants With Solid Tumors, Including Neuroblastoma

Baseline characteristics by cohort

Measure	Part A Cohort A1 n=7 Participants Participants received: * Abemaciclib: 70 mg/m², administered orally twice daily (BID). * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1 n=13 Participants Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 n=3 Participants Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 n=9 Participants Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 n=3 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 n=11 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part C Cohort C1 n=1 Participants Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. * Dinutuximab: 17.5mg/m²/day, administered IV on Days 2-5 of each cycle. * Granulocyte-macrophage colony-stimulating factor (GM-CSF): 250 μg/m²/day, administered subcutaneously (SC) on Days 6-12 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Total n=47 Participants Total of all reporting groups
Age, Continuous	12.9 years STANDARD_DEVIATION 3.3 • n=5 Participants	12.2 years STANDARD_DEVIATION 3.2 • n=7 Participants	12.3 years STANDARD_DEVIATION 4.7 • n=5 Participants	12.2 years STANDARD_DEVIATION 4.4 • n=4 Participants	9.3 years STANDARD_DEVIATION 3.5 • n=21 Participants	9.8 years STANDARD_DEVIATION 4.5 • n=8 Participants	7.00 years n=8 Participants	11.4 years STANDARD_DEVIATION 3.9 • n=24 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	6 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants	3 Participants n=21 Participants	6 Participants n=8 Participants	0 Participants n=8 Participants	23 Participants n=24 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	7 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants	0 Participants n=21 Participants	5 Participants n=8 Participants	1 Participants n=8 Participants	24 Participants n=24 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants	2 Participants n=8 Participants	0 Participants n=8 Participants	7 Participants n=24 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	7 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants	1 Participants n=21 Participants	9 Participants n=8 Participants	1 Participants n=8 Participants	35 Participants n=24 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	5 Participants n=24 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	7 Participants n=24 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	7 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants	3 Participants n=21 Participants	11 Participants n=8 Participants	1 Participants n=8 Participants	36 Participants n=24 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	3 Participants n=24 Participants
Region of Enrollment France	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	2 Participants n=24 Participants
Region of Enrollment Germany	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants	0 Participants n=8 Participants	8 Participants n=24 Participants
Region of Enrollment Italy	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	3 Participants n=24 Participants
Region of Enrollment Japan	3 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	5 Participants n=24 Participants
Region of Enrollment Spain	2 Participants n=5 Participants	7 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	10 Participants n=8 Participants	0 Participants n=8 Participants	27 Participants n=24 Participants
Region of Enrollment United States	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants	2 Participants n=24 Participants

PRIMARY outcome

Timeframe: Cycles 1 and 2 (21 Day Cycles)

Population: All participants in Part A who received at least one dose of abemaciclib and had evaluable data for this outcome.

The RP2D of abemaciclib was determined based on the totality of safety, tolerability, and pharmacokinetic results. RP2D of abemaciclib in combination with 50 mg/m²/day irinotecan and 100 mg/m²/day temozolomide on days 1-5 of 21-day cycles was reported.

Outcome measures

Measure	Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A - Abemaciclib n=20 Participants * Cohort A1: 70 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle. * Cohort A-1: 55 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle.	Part A Cohort A-1 Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
Recommended Phase 2 Dose (RP2D) of Abemaciclib in Combination With Irinotecan and Temozolomide (Part A)	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	55 milligrams/squared meters (mg/m²) BID	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 (21 Day Cycle)

Population: All participants in Part A who received at least one dose of the study drug and had evaluable data for this outcome.

DLT was 1 of the following adverse events likely related to abemaciclib/combination and fulfils any 1 of the following criteria graded per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0:

• Any non-hematologic Grade (G) ≥3 toxicity, except:

• G3 diarrhea lasting <72 hour (h)
• Acute irinotecan-associated diarrhea lasting <7 days
• G≥3 nausea, vomiting, constipation that lasts <72 h
• G3 mucositis/stomatitis lasting <72 h
• G3 fever/infection
• G≥3 electrolyte abnormality that lasts <72 h, is not complicated, and resolves spontaneously or responds to conventional medication;
• G≥3 amylase/lipase that is not associated with symptoms/clinical manifestations of pancreatitis; or
• AST/ALT elevation resolving to eligibility criteria within 7 days;
• Hematologic toxicities considered a DLT:

• A >14-day Cycle 2 delay due to neutropenia/thrombocytopenia
• G≥3 thrombocytopenia with significant bleeding; or
• G≥ 4 neutropenic fever

Outcome measures

Measure	Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A - Abemaciclib n=7 Participants * Cohort A1: 70 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle. * Cohort A-1: 55 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle.	Part A Cohort A-1 n=13 Participants Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
Number or Participants With Dose Limiting Toxicities (DLTs) in Part A	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	3 Participants	1 Participants	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 (21 Days)

Population: All part A participants who received at least one dose of abemaciclib and had evaluable data for this outcome.

The MTD was defined as the highest dose level at which less than 33% of participants experienced a DLT.

Outcome measures

Measure	Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A - Abemaciclib n=20 Participants * Cohort A1: 70 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle. * Cohort A-1: 55 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle.	Part A Cohort A-1 Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
Maximum Tolerated Dose (MTD) of Abemaciclib in Part A	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	55 mg/m² BID	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Pre-dose, 1, 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle)

Population: All participants in Part A who received at least one dose of abemaciclib and had evaluable PK data. Per planned analysis, PK analysis was performed as per the dose of study drug received.

PK: (AUC0-tlast) was reported.

Outcome measures

Measure	Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A - Abemaciclib n=6 Participants * Cohort A1: 70 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle. * Cohort A-1: 55 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle.	Part A Cohort A-1 n=13 Participants Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Tlast (AUC0-tlast) of Abemaciclib in Part A Cycle 1, Day 1	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	730 nanogram *hour per milliliter (ng*h/mL) Geometric Coefficient of Variation 33	534 nanogram *hour per milliliter (ng*h/mL) Geometric Coefficient of Variation 116	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Tlast (AUC0-tlast) of Abemaciclib in Part A Cycle 2, Day 1	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	NA nanogram *hour per milliliter (ng*h/mL) Geometric Coefficient of Variation NA Geometric Mean and Geometric Coefficient of Variation couldn't be calculated as there were only two participants. Individual values reported: 373.72 ng\*h/mL and 3373.97 ng\*h/mL.	757 nanogram *hour per milliliter (ng*h/mL) Geometric Coefficient of Variation 100	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle)

Population: All Part A participants who received at least one dose of irinotecan and had evaluable PK data. Per planned analysis, PK analysis was performed as per the dose of drug received.

PK: AUC0-tlast) was reported.

Outcome measures

Measure	Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A - Abemaciclib n=20 Participants * Cohort A1: 70 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle. * Cohort A-1: 55 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle.	Part A Cohort A-1 Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
PK: (AUC0-tlast) of Irinotecan in Part A Cycle 1, Day 1	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	1450 ng*h/mL Geometric Coefficient of Variation 37	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
PK: (AUC0-tlast) of Irinotecan in Part A Cycle 2, Day 1	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	1240 ng*h/mL Geometric Coefficient of Variation 58	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 1, 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle)

Population: All Part A participants who received at least one dose of temozolomide and had evaluable PK data. Per planned analysis, PK analysis was performed as per the dose of drug received.

PK: AUC0-tlast was reported.

Outcome measures

Measure	Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A - Abemaciclib n=19 Participants * Cohort A1: 70 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle. * Cohort A-1: 55 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle.	Part A Cohort A-1 Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
PK: (AUC0-tlast) of Temozolomide in Part A Cycle 1, Day 1	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	14400 ng*h/mL Geometric Coefficient of Variation 23	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
PK: (AUC0-tlast) of Temozolomide in Part A Cycle 2, Day 1	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	12200 ng*h/mL Geometric Coefficient of Variation 44	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycles 1 and 2 (21 Day Cycles)

Population: All participants in Part B who received at least one dose of abemaciclib and had evaluable data for this outcome.

The RP2D of abemaciclib was determined based on the totality of safety, tolerability, and pharmacokinetic results. RP2D of abemaciclib in combination with 150 mg/m²/day temozolomide on days 1-5 of 21-day cycles was reported.

Outcome measures

Measure	Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A - Abemaciclib n=26 Participants * Cohort A1: 70 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle. * Cohort A-1: 55 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle.	Part A Cohort A-1 Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
RP2D of Abemaciclib in Combination With Temozolomide (Part B)	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	115 mg/m² BID	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 (21 Day Cycle)

Population: All participants in Part B who received at least one dose of the study drug and had evaluable data for this outcome.

A DLT was 1 of the following adverse events likely related to abemaciclib/combination and fulfils any 1 of the following criteria graded as per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0:

• Any non-hematologic Grade (G) ≥3 toxicity, except:

• G3 diarrhea lasting <72 hr
• Acute irinotecan-associated diarrhea lasting <7 days
• G≥3 nausea, vomiting, constipation that lasts <72 hr
• G3 mucositis/stomatitis lasting <72 hr
• G3 fever/infection
• G≥3 electrolyte abnormality that lasts <72 hr, is not complicated, and resolves spontaneously or responds to conventional medication;
• G≥3 amylase/lipase that is not associated with symptoms/clinical manifestations of pancreatitis; or
• AST/ALT elevation resolving to eligibility criteria within 7 days;
• Hematologic toxicities considered a DLT:

• A >14-day Cycle 2 delay due to neutropenia/thrombocytopenia
• G≥3 thrombocytopenia with significant bleeding; or
• G≥ 4 neutropenic fever

Outcome measures

Measure	Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A - Abemaciclib n=3 Participants * Cohort A1: 70 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle. * Cohort A-1: 55 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle.	Part A Cohort A-1 n=9 Participants Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 n=3 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 n=11 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
Number or Participants With DLTs in Part B	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	0 Participants	1 Participants	0 Participants	1 Participants	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 (21 Days)

Population: All participants in Part B who received at least one dose of abemaciclib and had evaluable data for this outcome.

The MTD was defined as the highest dose level at which less than 33% of participants experienced a DLT.

Outcome measures

Measure	Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A - Abemaciclib n=26 Participants * Cohort A1: 70 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle. * Cohort A-1: 55 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle.	Part A Cohort A-1 Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
MTD of Abemaciclib in Part B	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	NA mg/m² BID Insufficient number of participants experienced DLT. Thus, MTD could not be calculated.	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Pre-dose, 1, 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle)

Population: All participants in Part B who received at least one dose of abemaciclib and had evaluable PK data. Per planned analysis, PK analysis was performed as per the dose of study drug received.

PK: AUC0-tlast was reported.

Outcome measures

Measure	Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A - Abemaciclib n=3 Participants * Cohort A1: 70 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle. * Cohort A-1: 55 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle.	Part A Cohort A-1 n=8 Participants Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 n=14 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
PK: AUC0-tlast of Abemaciclib in Part B Cycle 2, Day 1	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	NA ng*h/mL Geometric Coefficient of Variation NA Geometric Mean and Geometric Coefficient of Variation couldn't be calculated as there were only two participants. Individual values reported: 994.32 ng\*h/mL and 2247.03 ng\*h/mL.	600 ng*h/mL Geometric Coefficient of Variation 27	1060 ng*h/mL Geometric Coefficient of Variation 57	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
PK: AUC0-tlast of Abemaciclib in Part B Cycle 1, Day 1	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	566 ng*h/mL Geometric Coefficient of Variation 104	728 ng*h/mL Geometric Coefficient of Variation 60	728 ng*h/mL Geometric Coefficient of Variation 77	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 1, 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle)

Population: All Part B participants in who received at least one dose of temozolomide and had evaluable PK data. Per planned analysis, PK analysis was performed as per the dose of drug received.

PK: AUC0-tlast was reported.

Outcome measures

Measure	Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A - Abemaciclib n=13 Participants * Cohort A1: 70 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle. * Cohort A-1: 55 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle.	Part A Cohort A-1 n=11 Participants Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
PK: AUC0-tlast of Temozolomide in Part B Cycle 1, Day 1	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	15800 ng*h/mL Geometric Coefficient of Variation 19	24300 ng*h/mL Geometric Coefficient of Variation 13	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
PK: AUC0-tlast of Temozolomide in Part B Cycle 2, Day 1	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	15700 ng*h/mL Geometric Coefficient of Variation 21	21100 ng*h/mL Geometric Coefficient of Variation 43	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Date of first dose to disease progression or death (Up to 25 Months)

Population: All part C participants who received at least one dose of study drug. However, Part C was terminated early and only 1 participant was enrolled in this part.

ORR: Number of participants with best response of Complete Response (CR), Partial Response (PR), or Minor Response (MR) per International Neuroblastoma Response Criteria (INRC).

• CR is defined as complete response in all response components:

• Primary Tumor: <10 mm residual soft tissue primary site and complete resolution of MIBG-avid tumors
• Soft tissue and bone metastatic response: nonprimary target and nontarget lesions <10 mm and nodes identified as targets decreased to short axis <10mm and MIBG-avid update of nonprimary lesions completely resolved
• Bone marrow response: no tumor infiltration on reassessment; disappearance of all target lesions;
• PR is defined as PR in >1component and all other components are either CR, minimal disease (MD) (bone marrow only), PR (soft tissue or bone), or not involved (NI) and no components with progressive disease (PD).
• MR is defined PR or CR in >1 component and SD in >1 component and no component with PD

Outcome measures

Measure	Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A - Abemaciclib n=1 Participants * Cohort A1: 70 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle. * Cohort A-1: 55 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle.	Part A Cohort A-1 Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
Number of Participants With Overall Response Rate (ORR) in Part C.	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	1 Participants	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Date of first dose to disease progression or death (Up to 25 Months)

Population: All participants in Part A who received at least one dose of the study drug and had evaluable data for this outcome. Per pre-specified statistical analysis plan, analysis was performed as per the study treatments received.

ORR: Percentage of participants with best response of CR or PR per Response Evaluation Criteria in Solid Tumors (RECIST) or Response Assessment in Neuro-Oncology (RANO).

RECIST was used for solid tumors and RANO was used for brain tumors.

• CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO).
• PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and >50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO).

Outcome measures

Measure	Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A - Abemaciclib n=7 Participants * Cohort A1: 70 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle. * Cohort A-1: 55 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle.	Part A Cohort A-1 n=13 Participants Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
Percentage of Participants With Overall Response Rate (ORR): Part A	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	0 Percentage of participants None of the participants achieved ORR. Thus, upper and lower limit of confidence interval values could not be calculated.	7.7 Percentage of participants Interval 0.0 to 22.2	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Date of first dose to disease progression or death (Up to 25 Months)

Population: All participants in Part B who received at least one dose of the study drug and had evaluable data for this outcome. Per pre-specified statistical analysis plan, analysis was performed as per the study treatments received.

ORR: Percentage of participants with best response of CR or PR per Response Evaluation Criteria in Solid Tumors (RECIST) or Response Assessment in Neuro-Oncology (RANO).

RECIST was used for solid tumors and RANO was used for brain tumors.

• CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO).
• PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and >50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO).

Outcome measures

Measure	Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A - Abemaciclib n=3 Participants * Cohort A1: 70 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle. * Cohort A-1: 55 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle.	Part A Cohort A-1 n=9 Participants Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 n=3 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 n=11 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
Percentage of Participants With ORR: Part B	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	0 Percentage of participants None of the participants achieved ORR. Thus, upper and lower limits of confidence intervals could not be calculated.	0 Percentage of participants None of the participants achieved ORR. Thus, upper and lower limits of confidence intervals could not be calculated.	33.3 Percentage of participants Interval 0.0 to 86.7	18.2 Percentage of participants Interval 0.0 to 41.0	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Date of first evidence of a CR or PR to date of objective disease progression or death due to any cause (Up to 25 Months)

Population: All participants in Parts A and B who received at least one dose of the study drug and had evaluable data for this outcome. Per pre-specified statistical analysis plan, analysis was performed as per the study treatments received.

DoR is the time between first evidence of CR or PR and disease progression or death due to any cause.

RECIST was used for solid tumors and RANO was used for brain tumors.

• CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO).
• PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and >50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO).

Outcome measures

Measure	Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A - Abemaciclib * Cohort A1: 70 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle. * Cohort A-1: 55 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle.	Part A Cohort A-1 n=1 Participants Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 n=1 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 n=2 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
Duration of Response (DoR): Parts A and B.	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	22.59 Months Only 1 participant had events, hence confidence interval limits could not be calculated.	—	—	7.82 Months Only 1 participant had events, hence confidence interval limits could not be calculated.	0.03 Months Upper and lower limit confidence intervals cannot be calculated as both participants had the same Duration of Response of 0.03 months.	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Date of first evidence of a CR, PR, or MR to date of objective disease progression or death due to any cause (Up to 25 Months)

Population: All participants in Part C who received at least one dose of the study drug and had evaluable data for this outcome.

DoR is the time between first evidence of CR, PR or MR and disease progression or death due to any cause.

CR, PR, and MR was as per International Neuroblastoma Response Criteria (INRC).

• CR is defined as complete response in all response components: Primary Tumor: <10 mm residual soft tissue primary site and complete resolution of MIBG-avid tumors Soft tissue and bone metastatic response: nonprimary target and nontarget lesions <10 mm and nodes identified as targets decreased to short axis <10mm and MIBG-avid update of nonprimary lesions completely resolved Bone marrow response: no tumor infiltration on reassessment; disappearance of all target lesions;

• PR is defined as PR in >1 component and all other components are either CR, minimal disease (MD) (bone marrow only), PR (soft tissue or bone), or not involved (NI) and no components with progressive disease (PD).
• MR is defined PR or CR in >1 component and SD in >1 component and no component with PD

Outcome measures

Measure	Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A - Abemaciclib n=1 Participants * Cohort A1: 70 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle. * Cohort A-1: 55 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle.	Part A Cohort A-1 Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
Duration of Response (DoR): Part C	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	1.61 Months Only 1 participant had events, hence confidence interval limits could not be calculated.	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Date of first dose to disease progression or death due to any cause (Up to 25 Months)

Population: All participants in Part A who received at least one dose of the study drug and had evaluable data for this outcome. Per pre-specified statistical analysis plan, analysis was performed as per the study treatments received.

The CBR is the percentage of participants with a best response of CR or PR, or Stable Disease (SD) for at least 6 months.

RECIST was used for solid tumors and RANO was used for brain tumors.

• CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO).
• PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and >50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO).
• SD is neither sufficient shrinkage nor sufficient increase in the size of the tumor.

Outcome measures

Measure	Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A - Abemaciclib n=7 Participants * Cohort A1: 70 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle. * Cohort A-1: 55 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle.	Part A Cohort A-1 n=13 Participants Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
Percentage of Participants With Clinical Benefit Rate (CBR): Part A	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	14.3 Percentage of participants Interval 0.0 to 40.2	30.8 Percentage of participants Interval 5.7 to 55.9	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Date of first dose to disease progression or death due to any cause (Up to 25 Months)

Population: All participants in Part B who received at least one dose of the study drug and had evaluable data for this outcome. Per pre-specified statistical analysis plan, analysis was performed as per the study treatments received.

The CBR is the percentage of participants with a best response of CR or PR, or SD for at least 6 months.

RECIST was used for solid tumors and RANO was used for brain tumors.

• CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO).
• PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and >50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO).
• SD is neither sufficient shrinkage nor sufficient increase in the size of the tumor.

Outcome measures

Measure	Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A - Abemaciclib n=3 Participants * Cohort A1: 70 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle. * Cohort A-1: 55 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle.	Part A Cohort A-1 n=9 Participants Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 n=3 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 n=11 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
Percentage of Participants With CBR: Part B	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	33.3 Percentage of participants Interval 0.0 to 86.7	0 Percentage of participants None of the participants achieved CBR. Thus, upper and lower limits of confidence intervals could not be calculated.	33.3 Percentage of participants Interval 0.0 to 86.7	18.2 Percentage of participants Interval 0.0 to 41.0	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Date of first dose to measured progressive disease (Up to 25 Months)

Population: All participants in Part A who received at least one dose of the study drug and had evaluable data for this outcome. Per pre-specified statistical analysis plan, analysis was performed as per the study treatments received.

DCR: Percentage of participants with a best overall response of CR, PR, and SD. RECIST was used for solid tumors and RANO was used for brain tumors.

• CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO).
• PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and >50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO).
• SD is neither sufficient shrinkage nor sufficient increase in the size of the tumor.

Outcome measures

Measure	Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A - Abemaciclib n=7 Participants * Cohort A1: 70 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle. * Cohort A-1: 55 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle.	Part A Cohort A-1 n=13 Participants Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
Percentage of Participants With Disease Control Rate (DCR): Part A	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	71.4 Percentage of participants Interval 38.0 to 100.0	53.8 Percentage of participants Interval 26.7 to 80.9	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Date of first dose to measured progressive disease (Up to 25 Months)

Population: All participants in Part B who received at least one dose of the study drug and had evaluable data for this outcome. Per pre-specified statistical analysis plan, analysis was performed as per the study treatments received.

DCR: Percentage of participants with a best overall response of CR, PR, and SD. RECIST was used for solid tumors and RANO was used for brain tumors.

• CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO).
• PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and >50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO).
• SD is neither sufficient shrinkage nor sufficient increase in the size of the tumor.

Outcome measures

Measure	Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A - Abemaciclib n=3 Participants * Cohort A1: 70 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle. * Cohort A-1: 55 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle.	Part A Cohort A-1 n=9 Participants Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 n=3 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 n=11 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
Percentage of Participants With DCR: Part B	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	33.3 Percentage of participants Interval 0.0 to 86.7	55.6 Percentage of participants Interval 23.1 to 88.0	100 Percentage of participants Interval 100.0 to 100.0	36.4 Percentage of participants Interval 7.9 to 64.8	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Date of first dose to progressive disease or death (Up to 25 Months)

Population: All part C participants who received at least one dose of study drug. However, Part C was terminated early and only 1 participant was enrolled in this part.

Progression-free survival is measured as the time from first dose of study drug to progressive disease or death, whichever occurs first. PFS for Part C was reported.

Outcome measures

Measure	Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A - Abemaciclib n=1 Participants * Cohort A1: 70 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle. * Cohort A-1: 55 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle.	Part A Cohort A-1 Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
Progression-Free Survival (PFS): Part C	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	2.9 Months	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (21 Day Cycles)

Population: All participants in Parts A and B, who received at least one dose of abemaciclib and had evaluable data for this outcome. Per protocol, data were summarized by responses provided by participants, and/or caregivers on the acceptability of the abemaciclib received on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1.

Participants were evaluated for abemaciclib acceptability (palatability and ease of administration) by asking a question - " Was it easy or difficult for the study subject to swallow the abemaciclib today?" Participants or their caregivers or both could respond using the following possible answers: Very difficult, difficult, neither easy nor difficult, easy, or very easy.

Outcome measures

Measure	Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) n=6 Participants Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) n=6 Participants Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) n=6 Participants Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) n=1 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) n=1 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) n=1 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) n=3 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) n=3 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) n=3 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) n=6 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) n=7 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) n=4 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) n=9 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) n=9 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) n=9 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A - Abemaciclib n=3 Participants * Cohort A1: 70 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle. * Cohort A-1: 55 mg/m² abemaciclib administered orally BID in combination with 50 mg/m²/day irinotecan administered IV on Days 1-5 of each 21-day cycle and 100 mg/m²/day temozolomide administered orally on Days 1-5 of each 21-day cycle.	Part A Cohort A-1 n=2 Participants Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 n=5 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 n=7 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 n=5 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 n=6 Participants Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) n=6 Participants Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) n=4 Participants Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) n=7 Participants Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) n=10 Participants Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) n=8 Participants Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) n=8 Participants Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) n=2 Participants Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) n=1 Participants Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) n=1 Participants Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) n=2 Participants Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) n=1 Participants Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) n=2 Participants Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) n=5 Participants Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) n=4 Participants Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) n=4 Participants Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
Abemaciclib Tablet Acceptability Very difficult to swallow tablet	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Abemaciclib Tablet Acceptability Easy to swallow tablet	0 Participants	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	2 Participants	1 Participants	2 Participants	3 Participants	1 Participants	2 Participants	0 Participants	0 Participants	1 Participants	4 Participants	3 Participants	3 Participants	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	2 Participants
Abemaciclib Tablet Acceptability Neither easy nor difficult to swallow tablet	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Abemaciclib Tablet Acceptability Difficult to swallow tablet	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Abemaciclib Tablet Acceptability Very easy to swallow tablet	5 Participants	5 Participants	3 Participants	0 Participants	1 Participants	1 Participants	3 Participants	3 Participants	3 Participants	3 Participants	6 Participants	4 Participants	6 Participants	8 Participants	9 Participants	1 Participants	1 Participants	3 Participants	4 Participants	4 Participants	4 Participants	6 Participants	4 Participants	6 Participants	6 Participants	4 Participants	5 Participants	1 Participants	0 Participants	0 Participants	2 Participants	1 Participants	2 Participants	3 Participants	3 Participants	2 Participants

Adverse Events

Part A Cohort A1

Serious events: 3 serious events

Other events: 7 other events

Deaths: 1 deaths

Part A Cohort A-1

Serious events: 5 serious events

Other events: 13 other events

Deaths: 1 deaths

Part B Cohort B1

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Part B Cohort B2

Serious events: 0 serious events

Other events: 8 other events

Deaths: 1 deaths

Part B Cohort B3

Serious events: 0 serious events

Other events: 3 other events

Deaths: 1 deaths

Part B Cohort B5

Serious events: 3 serious events

Other events: 11 other events

Deaths: 1 deaths

Part C Cohort C1

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Part A Cohort A1 n=7 participants at risk Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1 n=13 participants at risk Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 n=3 participants at risk Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 n=9 participants at risk Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 n=3 participants at risk Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 n=11 participants at risk Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part C Cohort C1 n=1 participants at risk Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. * Dinutuximab: 17.5mg/m²/day, administered IV on Days 2-5 of each cycle. * GM-CSF: 250 μg/m²/day, administered SC on Days 6-12 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
Nervous system disorders Seizure	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Neuropathy	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Blood and lymphatic system disorders Febrile neutropenia	28.6% 2/7 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Abdominal pain	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Diarrhoea	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Vomiting	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
General disorders Pyrexia	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Respiratory syncytial virus infection	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Metabolism and nutrition disorders Dehydration	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Cognitive disorder	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Depressed level of consciousness	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Headache	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Skin and subcutaneous tissue disorders Vancomycin infusion reaction	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.

Other adverse events

Measure	Part A Cohort A1 n=7 participants at risk Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part A Cohort A-1 n=13 participants at risk Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B1 n=3 participants at risk Participants received: * Abemaciclib: 70 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B2 n=9 participants at risk Participants received: * Abemaciclib: 90 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B3 n=3 participants at risk Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part B Cohort B5 n=11 participants at risk Participants received: * Abemaciclib: 115 mg/m², administered orally BID. * Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.	Part C Cohort C1 n=1 participants at risk Participants received: * Abemaciclib: 55 mg/m², administered orally BID. * Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle. * Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle. * Dinutuximab: 17.5mg/m²/day, administered IV on Days 2-5 of each cycle. * GM-CSF: 250 μg/m²/day, administered SC on Days 6-12 of each cycle. Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days.
Infections and infestations Herpes virus infection	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Herpes zoster	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Influenza	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Nasopharyngitis	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Onychomycosis	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Oral candidiasis	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Pharyngitis	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Pneumonia	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Pneumonia streptococcal	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Respiratory tract infection	14.3% 1/7 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	18.2% 2/11 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Rhinitis	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Superinfection	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Upper respiratory tract infection	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	27.3% 3/11 • Number of events 4 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Psychiatric disorders Psychotic disorder	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Urinary tract infection	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Injury, poisoning and procedural complications Contusion	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Injury, poisoning and procedural complications Fall	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Injury, poisoning and procedural complications Mouth injury	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Psychiatric disorders Restlessness	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Injury, poisoning and procedural complications Periorbital haematoma	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Investigations Alanine aminotransferase increased	57.1% 4/7 • Number of events 13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	30.8% 4/13 • Number of events 9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	18.2% 2/11 • Number of events 3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Investigations Aspartate aminotransferase increased	57.1% 4/7 • Number of events 10 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	23.1% 3/13 • Number of events 6 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	27.3% 3/11 • Number of events 6 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Investigations Blood alkaline phosphatase increased	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Investigations Blood bilirubin increased	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Investigations Blood creatine increased	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Investigations Blood creatinine increased	28.6% 2/7 • Number of events 5 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	22.2% 2/9 • Number of events 5 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	66.7% 2/3 • Number of events 4 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	45.5% 5/11 • Number of events 10 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Investigations Blood lactate dehydrogenase increased	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Investigations Blood urea increased	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Investigations Cystatin c increased	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Investigations Gamma-glutamyltransferase increased	14.3% 1/7 • Number of events 3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	27.3% 3/11 • Number of events 3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Investigations International normalised ratio increased	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Investigations Weight decreased	42.9% 3/7 • Number of events 3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	46.2% 6/13 • Number of events 19 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	66.7% 2/3 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	22.2% 2/9 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Psychiatric disorders Sleep disorder	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Metabolism and nutrition disorders Decreased appetite	71.4% 5/7 • Number of events 9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	23.1% 3/13 • Number of events 4 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 6 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Metabolism and nutrition disorders Dehydration	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Metabolism and nutrition disorders Folate deficiency	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Metabolism and nutrition disorders Hyperphosphataemia	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	27.3% 3/11 • Number of events 5 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Metabolism and nutrition disorders Hypoalbuminaemia	57.1% 4/7 • Number of events 4 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	15.4% 2/13 • Number of events 4 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Metabolism and nutrition disorders Hypokalaemia	28.6% 2/7 • Number of events 3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	23.1% 3/13 • Number of events 7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	66.7% 2/3 • Number of events 3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Metabolism and nutrition disorders Hypomagnesaemia	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Metabolism and nutrition disorders Hyponatraemia	28.6% 2/7 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Metabolism and nutrition disorders Hypophagia	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Metabolism and nutrition disorders Hypophosphataemia	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	15.4% 2/13 • Number of events 5 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	66.7% 2/3 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	18.2% 2/11 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Metabolism and nutrition disorders Vitamin b12 deficiency	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Renal and urinary disorders Cystitis noninfective	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Metabolism and nutrition disorders Vitamin d deficiency	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	18.2% 2/11 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Musculoskeletal and connective tissue disorders Arthralgia	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Musculoskeletal and connective tissue disorders Back pain	28.6% 2/7 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Renal and urinary disorders Dysuria	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Musculoskeletal and connective tissue disorders Limb discomfort	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Musculoskeletal and connective tissue disorders Muscle atrophy	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	22.2% 2/9 • Number of events 5 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	18.2% 2/11 • Number of events 4 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Musculoskeletal and connective tissue disorders Pain in extremity	28.6% 2/7 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	15.4% 2/13 • Number of events 3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Anterograde amnesia	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Ataxia	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Cognitive disorder	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Depressed level of consciousness	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Disturbance in attention	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Dental caries	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Dizziness	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 6 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Dysgeusia	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Facial nerve disorder	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Facial paralysis	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Headache	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	23.1% 3/13 • Number of events 4 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	18.2% 2/11 • Number of events 3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Diarrhoea	100.0% 7/7 • Number of events 18 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 13/13 • Number of events 65 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	55.6% 5/9 • Number of events 22 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 3/3 • Number of events 6 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	81.8% 9/11 • Number of events 24 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Hemiparesis	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Hypotonia	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Lethargy	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Memory impairment	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Neuropathy	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Paresis	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Peripheral motor neuropathy	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Seizure	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	15.4% 2/13 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Nervous system disorders Tremor	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Product Issues Device malfunction	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Psychiatric disorders Anxiety	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Psychiatric disorders Confusional state	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Psychiatric disorders Insomnia	28.6% 2/7 • Number of events 4 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	15.4% 2/13 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Blood and lymphatic system disorders Anaemia	71.4% 5/7 • Number of events 11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	61.5% 8/13 • Number of events 17 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	55.6% 5/9 • Number of events 5 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	63.6% 7/11 • Number of events 9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Blood and lymphatic system disorders Febrile neutropenia	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Blood and lymphatic system disorders Leukopenia	85.7% 6/7 • Number of events 16 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	30.8% 4/13 • Number of events 21 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	22.2% 2/9 • Number of events 9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	66.7% 2/3 • Number of events 3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	72.7% 8/11 • Number of events 13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Blood and lymphatic system disorders Lymphopenia	57.1% 4/7 • Number of events 4 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	30.8% 4/13 • Number of events 4 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	27.3% 3/11 • Number of events 5 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Blood and lymphatic system disorders Neutropenia	85.7% 6/7 • Number of events 25 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	76.9% 10/13 • Number of events 35 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	66.7% 2/3 • Number of events 3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	66.7% 6/9 • Number of events 17 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 3/3 • Number of events 10 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	72.7% 8/11 • Number of events 20 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Blood and lymphatic system disorders Thrombocytopenia	71.4% 5/7 • Number of events 15 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	61.5% 8/13 • Number of events 29 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	66.7% 2/3 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	44.4% 4/9 • Number of events 8 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	66.7% 2/3 • Number of events 7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	81.8% 9/11 • Number of events 16 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Cardiac disorders Palpitations	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Congenital, familial and genetic disorders Hydrocele	0.00% 0/5 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/5 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/5 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Ear and labyrinth disorders Ear pain	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Endocrine disorders Cushing's syndrome	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Endocrine disorders Hypothyroidism	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Eye disorders Anisocoria	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Eye disorders Blepharospasm	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Eye disorders Conjunctival hyperaemia	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Eye disorders Eczema eyelids	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Eye disorders Keratitis	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Eye disorders Ophthalmoplegia	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Eye disorders Vision blurred	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Abdominal distension	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Abdominal pain	57.1% 4/7 • Number of events 10 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	46.2% 6/13 • Number of events 11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	22.2% 2/9 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	66.7% 2/3 • Number of events 7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	36.4% 4/11 • Number of events 7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Anal fissure	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Anal pruritus	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Anal rash	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Colitis	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Constipation	57.1% 4/7 • Number of events 9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Dyspepsia	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Dysphagia	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Gastritis	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Gastrooesophageal reflux disease	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Haemorrhoids	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Ileus	14.3% 1/7 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Large intestinal haemorrhage	14.3% 1/7 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Nausea	71.4% 5/7 • Number of events 17 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	38.5% 5/13 • Number of events 13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	22.2% 2/9 • Number of events 4 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	36.4% 4/11 • Number of events 4 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Oral pain	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Rectal haemorrhage	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Tongue atrophy	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Gastrointestinal disorders Vomiting	85.7% 6/7 • Number of events 18 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	53.8% 7/13 • Number of events 21 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	66.7% 6/9 • Number of events 12 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	66.7% 2/3 • Number of events 3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	45.5% 5/11 • Number of events 10 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
General disorders Catheter site erythema	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
General disorders Fatigue	14.3% 1/7 • Number of events 3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	38.5% 5/13 • Number of events 6 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	22.2% 2/9 • Number of events 3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	18.2% 2/11 • Number of events 5 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
General disorders Gait disturbance	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
General disorders Hypothermia	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
General disorders Influenza like illness	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
General disorders Oedema peripheral	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
General disorders Pain	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 4 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
General disorders Pyrexia	14.3% 1/7 • Number of events 3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	15.4% 2/13 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	22.2% 2/9 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	27.3% 3/11 • Number of events 5 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Abdominal infection	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Bacterial diarrhoea	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Clostridium difficile infection	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Conjunctivitis	28.6% 2/7 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Covid-19	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Ear infection	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Gastroenteritis	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Gastroenteritis cryptosporidial	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Genital infection	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Infections and infestations Herpes dermatitis	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Renal and urinary disorders Renal pain	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Reproductive system and breast disorders Genital rash	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Renal and urinary disorders Urinary incontinence	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Renal and urinary disorders Haematuria	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Reproductive system and breast disorders Testicular pain	0.00% 0/5 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/5 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	20.0% 1/5 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Reproductive system and breast disorders Vulvovaginal inflammation	0.00% 0/2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/6 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/4 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	16.7% 1/6 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Respiratory, thoracic and mediastinal disorders Cough	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	66.7% 2/3 • Number of events 3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	18.2% 2/11 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Respiratory, thoracic and mediastinal disorders Dyspnoea	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	33.3% 1/3 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	14.3% 1/7 • Number of events 2 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Respiratory, thoracic and mediastinal disorders Pneumomediastinum	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Respiratory, thoracic and mediastinal disorders Sneezing	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	23.1% 3/13 • Number of events 3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Skin and subcutaneous tissue disorders Pruritus	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Skin and subcutaneous tissue disorders Rash	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	11.1% 1/9 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	9.1% 1/11 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	100.0% 1/1 • Number of events 3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Skin and subcutaneous tissue disorders Skin lesion	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Vascular disorders Hot flush	14.3% 1/7 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/13 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.
Vascular disorders Superficial vein thrombosis	0.00% 0/7 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	7.7% 1/13 • Number of events 1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/9 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/3 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/11 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.	0.00% 0/1 • Baseline Up To 112 Weeks All participants who received at least one dose of the study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. The adverse events were analyzed and reported according to the study treatments pre-specified in the protocol.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: ClinicalTrials.gov@lilly.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60