Trial Outcomes & Findings for A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer, Non-small Cell Lung Cancer, or Melanoma That Has Spread to the Brain (NCT NCT02308020)

Last Updated: 2020-12-19

Results Overview

OIRR is the percentage of participants with a (CR) or (PR) based on the Response Assessment in Neuro-Oncology Brain Metastasis (RANO-BM) response criteria. CR is measurable target lesions, the disappearance of all central nervous system (CNS) target lesions for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically. PR is at least a 30% decrease in the sum longest duration (LD) of CNS target lesions, taking as reference the baseline sum LD for at least 4 weeks; no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. Nontarget lesions requires disappearance CNS non-target lesions and no new CNS lesions. Stable disease (SD) is less than (\<)30% decrease relative to baseline but \<20% increase in sum LD relative to nadir. Progressive disease (PD) is greater than or equal to (≥) 20% increase in sum LD relative to nadir and a relative increase of 20%, ≥1 lesion must increase by absolute value of ≥5 millimeter (mm).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

162 participants

Primary outcome timeframe

Baseline to Objective Disease Progression (Up to 36 Months)

Results posted on

2020-12-19

Participant Flow

Completers include participants who died or discontinued study treatment due to progressive disease and is in follow up.

Participant milestones

Participant milestones
Measure	Part A Abemaciclib: Hormone Receptor (HR+) HER2+ Breast Cancer Abemaciclib 200 milligram (mg) was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or in combination with endocrine therapy (ET). Participants with hormone receptor positive (HR+), hormone epidermal growth factor receptor 2 positive (HER2+) breast cancer receiving concurrent trastuzumab, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part B Abemaciclib: HR+, HER2- Breast Cancer Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or in combination with endocrine therapy (ET). Participants may continue to receive treatment until discontinuation criteria are met.	Part C Abemaciclib: Surgical Resection Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for participants with breast cancer in combination with endocrine therapy (ET). Participants with HR+, HER2+ breast cancer, NSCLC, or melanoma with intracranial lesions for which surgical resection is clinically indicated receiving concurrent trastuzumab, gemcitabine, or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours for 5-14 days prior to surgical resection. Dosing may resume following wound healing on a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part D Abemaciclib: Non-Small Cell Lung Cancer (NSCLC) Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants with NSCLC receiving concurrent gemcitabine or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part E Abemaciclib: Melanoma Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part F Abemaciclib: HR+ Breast Cancer, NSCLC, or Melanoma Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for participants with breast cancer in combination with endocrine therapy (ET). Participants with HR+ (either HER2+ or HER2-) breast cancer, NSCLC, or melanoma and leptomeningeal metastases received concurrent trastuzumab, gemcitabine, or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Overall Study STARTED	27	58	9	28	23	17
Overall Study Received at Least One Dose of Study Drug	27	58	9	28	23	17
Overall Study COMPLETED	23	38	6	24	19	12
Overall Study NOT COMPLETED	4	20	3	4	4	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A Abemaciclib: Hormone Receptor (HR+) HER2+ Breast Cancer Abemaciclib 200 milligram (mg) was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or in combination with endocrine therapy (ET). Participants with hormone receptor positive (HR+), hormone epidermal growth factor receptor 2 positive (HER2+) breast cancer receiving concurrent trastuzumab, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part B Abemaciclib: HR+, HER2- Breast Cancer Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or in combination with endocrine therapy (ET). Participants may continue to receive treatment until discontinuation criteria are met.	Part C Abemaciclib: Surgical Resection Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for participants with breast cancer in combination with endocrine therapy (ET). Participants with HR+, HER2+ breast cancer, NSCLC, or melanoma with intracranial lesions for which surgical resection is clinically indicated receiving concurrent trastuzumab, gemcitabine, or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours for 5-14 days prior to surgical resection. Dosing may resume following wound healing on a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part D Abemaciclib: Non-Small Cell Lung Cancer (NSCLC) Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants with NSCLC receiving concurrent gemcitabine or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part E Abemaciclib: Melanoma Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part F Abemaciclib: HR+ Breast Cancer, NSCLC, or Melanoma Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for participants with breast cancer in combination with endocrine therapy (ET). Participants with HR+ (either HER2+ or HER2-) breast cancer, NSCLC, or melanoma and leptomeningeal metastases received concurrent trastuzumab, gemcitabine, or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Overall Study Lost to Follow-up	1	7	0	0	1	2
Overall Study Sponsor Decision	0	8	0	2	2	1
Overall Study Withdrawal by Subject	3	5	3	2	1	2

Baseline Characteristics

A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer, Non-small Cell Lung Cancer, or Melanoma That Has Spread to the Brain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A Abemaciclib: HR+, HER2+ Breast Cancer n=27 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or in combination with endocrine therapy (ET). Participants with hormone receptor positive HR+, HER2+ breast cancer receiving concurrent trastuzumab, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part B Abemaciclib: HR+, HER2- Breast Cancer n=58 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or in combination with endocrine therapy (ET). Participants may continue to receive treatment until discontinuation criteria are met.	Part C Abemaciclib: Surgical Resection n=9 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for participants with breast cancer in combination with endocrine therapy (ET). Participants with HR+, HER2+ breast cancer, NSCLC, or melanoma with intracranial lesions for which surgical resection is clinically indicated receiving concurrent trastuzumab, gemcitabine, or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours for 5-14 days prior to surgical resection. Dosing may resume following wound healing on a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part D Abemaciclib: NSCLC n=28 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants with NSCLC receiving concurrent gemcitabine or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part E Abemaciclib: Melanoma n=23 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part F Abemaciclib: HR+ Breast Cancer, NSCLC, or Melanoma n=17 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for participants with breast cancer in combination with endocrine therapy (ET). Participants with HR+ (either HER2+ or HER2-) breast cancer, NSCLC, or melanoma and leptomeningeal metastases received concurrent trastuzumab, gemcitabine, or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Total n=162 Participants Total of all reporting groups
Age, Continuous	49.9 years STANDARD_DEVIATION 10.9 • n=93 Participants	54.1 years STANDARD_DEVIATION 10.5 • n=4 Participants	57.0 years STANDARD_DEVIATION 17.9 • n=27 Participants	58.4 years STANDARD_DEVIATION 10.9 • n=483 Participants	55.1 years STANDARD_DEVIATION 14.4 • n=36 Participants	50.1 years STANDARD_DEVIATION 12.3 • n=10 Participants	54.0 years STANDARD_DEVIATION 12.1 • n=115 Participants
Sex: Female, Male Female	27 Participants n=93 Participants	57 Participants n=4 Participants	8 Participants n=27 Participants	14 Participants n=483 Participants	11 Participants n=36 Participants	14 Participants n=10 Participants	131 Participants n=115 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	14 Participants n=483 Participants	12 Participants n=36 Participants	3 Participants n=10 Participants	31 Participants n=115 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	3 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants	1 Participants n=10 Participants	5 Participants n=115 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=93 Participants	42 Participants n=4 Participants	8 Participants n=27 Participants	20 Participants n=483 Participants	20 Participants n=36 Participants	14 Participants n=10 Participants	125 Participants n=115 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=93 Participants	13 Participants n=4 Participants	1 Participants n=27 Participants	8 Participants n=483 Participants	2 Participants n=36 Participants	2 Participants n=10 Participants	32 Participants n=115 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	3 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	5 Participants n=115 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	4 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	0 Participants n=36 Participants	1 Participants n=10 Participants	7 Participants n=115 Participants
Race (NIH/OMB) White	17 Participants n=93 Participants	35 Participants n=4 Participants	7 Participants n=27 Participants	20 Participants n=483 Participants	22 Participants n=36 Participants	14 Participants n=10 Participants	115 Participants n=115 Participants
Race (NIH/OMB) More than one race	1 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	2 Participants n=115 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants n=93 Participants	15 Participants n=4 Participants	1 Participants n=27 Participants	7 Participants n=483 Participants	1 Participants n=36 Participants	2 Participants n=10 Participants	33 Participants n=115 Participants
Region of Enrollment Canada	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	2 Participants n=10 Participants	3 Participants n=115 Participants
Region of Enrollment Austria	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants
Region of Enrollment Belgium	4 Participants n=93 Participants	8 Participants n=4 Participants	0 Participants n=27 Participants	3 Participants n=483 Participants	3 Participants n=36 Participants	0 Participants n=10 Participants	18 Participants n=115 Participants
Region of Enrollment United States	11 Participants n=93 Participants	24 Participants n=4 Participants	7 Participants n=27 Participants	12 Participants n=483 Participants	7 Participants n=36 Participants	10 Participants n=10 Participants	71 Participants n=115 Participants
Region of Enrollment Italy	0 Participants n=93 Participants	4 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants	9 Participants n=36 Participants	0 Participants n=10 Participants	15 Participants n=115 Participants
Region of Enrollment Israel	1 Participants n=93 Participants	2 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants	1 Participants n=10 Participants	6 Participants n=115 Participants
Region of Enrollment Australia	2 Participants n=93 Participants	2 Participants n=4 Participants	1 Participants n=27 Participants	2 Participants n=483 Participants	1 Participants n=36 Participants	1 Participants n=10 Participants	9 Participants n=115 Participants
Region of Enrollment France	7 Participants n=93 Participants	14 Participants n=4 Participants	1 Participants n=27 Participants	7 Participants n=483 Participants	1 Participants n=36 Participants	2 Participants n=10 Participants	32 Participants n=115 Participants
Region of Enrollment Spain	2 Participants n=93 Participants	2 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants	1 Participants n=10 Participants	7 Participants n=115 Participants

PRIMARY outcome

Timeframe: Baseline to Objective Disease Progression (Up to 36 Months)

Population: All participants who had evaluable OIRR data with at least one measurable brain lesion at baseline (per RANO-BM) and for whom at least one post-baseline overall response assessment for intracranial disease is available. Parts C and F were exploratory per protocol.

Outcome measures

Outcome measures
Measure	Part E Abemaciclib: Melanoma n=22 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part A 150 mg Abemaciclib: HR+, HER2+ Breast Cancer n=23 Participants Participants with HR+, HER2+ breast cancer received 150 mg abemaciclib orally once every 12 hours on days 1-21 of a 21-day cycle.	Part B 200 mg Abemaciclib: HR+, HER2- Breast Cancer n=52 Participants Participants with HR+, HER2- breast cancer received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.	Part D Abemaciclib: NSCLC n=23 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants with NSCLC receiving concurrent gemcitabine or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part E 200 mg Abemaciclib: Melanoma Participants with melanoma received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.	Part F 200 mg Abemaciclib: HR+ Breast Cancer, NSCLC, Melanoma Participants with HR+ (either HER2+ or HER2-) breast cancer, NSCLC, or melanoma and leptomeningeal metastases received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Intracranial Response Rate (OIRR)	0 percentage of participants	0 percentage of participants	5.8 percentage of participants	0 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline to Earliest Objective Progression or Start of New Anticancer Therapy (Up to 36 Months)

Percentage of Participants with BOIR was categorized as CR, PR, SD, PD or NE, as defined by RANO-BM, from baseline until the earliest of objective progression according to brain metastases response criteria or start of new anticancer therapy. CR is measurable target lesions, the disappearance of all CNS target lesions for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically. PR is at least a 30% decrease in the sum LD of CNS target lesions, taking as reference the baseline sum LD for at least 4 weeks; no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. SD is \<30% decrease relative to baseline but \<20% increase in sum LD relative to nadir. PD is greater than or equal to (≥) 20% increase in sum LD relative to nadir and a relative increase of 20%, ≥1 lesion must increase by absolute value of ≥5 mm. NE is absent (no abnormality; normal), or non-evaluable (NE).

Outcome measures

Outcome measures
Measure	Part E Abemaciclib: Melanoma n=22 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part A 150 mg Abemaciclib: HR+, HER2+ Breast Cancer n=23 Participants Participants with HR+, HER2+ breast cancer received 150 mg abemaciclib orally once every 12 hours on days 1-21 of a 21-day cycle.	Part B 200 mg Abemaciclib: HR+, HER2- Breast Cancer n=52 Participants Participants with HR+, HER2- breast cancer received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.	Part D Abemaciclib: NSCLC n=23 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants with NSCLC receiving concurrent gemcitabine or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part E 200 mg Abemaciclib: Melanoma Participants with melanoma received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.	Part F 200 mg Abemaciclib: HR+ Breast Cancer, NSCLC, Melanoma Participants with HR+ (either HER2+ or HER2-) breast cancer, NSCLC, or melanoma and leptomeningeal metastases received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.
Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR) Partial Response	0 percentage of participants	0 percentage of participants	5.8 percentage of participants	0 percentage of participants	—	—
Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR) Stable Disease	31.8 percentage of participants	52.2 percentage of participants	65.4 percentage of participants	43.5 percentage of participants	—	—
Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR) Progressive Disease	68.2 percentage of participants	47.8 percentage of participants	28.8 percentage of participants	56.5 percentage of participants	—	—
Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR) Not Evaluable	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	—	—

SECONDARY outcome

Timeframe: Date of CR or PR to Date of Objective Disease Progression or Death from Any Cause (Up to 36 Months)

Population: All participants who had a confirmed intracranial response of CR or PR (per RANO-BM) and for whom at least one post-baseline overall intracranial response with a measurable duration is available. Parts C and F were exploratory per protocol.

DOIR is measured from the date of first evidence of a confirmed response (CR or PR), as defined by RANO-BM, to the date objective progression or death from any cause. CR is measurable target lesions, the disappearance of all CNS target lesions for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically. PR is at least a 30% decrease in the sum LD of CNS target lesions, taking as reference the baseline sum LD for at least 4 weeks; no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. Participants who have neither progressed nor died were censored on the day of their last radiographic tumor assessment or on the date of response. PD is greater than or equal to (≥) 20% increase in sum LD relative to nadir and a relative increase of 20%, ≥1 lesion must increase by absolute value of ≥5 mm. DOIR was summarized using Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Part E Abemaciclib: Melanoma Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part A 150 mg Abemaciclib: HR+, HER2+ Breast Cancer Participants with HR+, HER2+ breast cancer received 150 mg abemaciclib orally once every 12 hours on days 1-21 of a 21-day cycle.	Part B 200 mg Abemaciclib: HR+, HER2- Breast Cancer n=3 Participants Participants with HR+, HER2- breast cancer received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.	Part D Abemaciclib: NSCLC Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants with NSCLC receiving concurrent gemcitabine or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part E 200 mg Abemaciclib: Melanoma Participants with melanoma received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.	Part F 200 mg Abemaciclib: HR+ Breast Cancer, NSCLC, Melanoma Participants with HR+ (either HER2+ or HER2-) breast cancer, NSCLC, or melanoma and leptomeningeal metastases received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.
Duration of CR or PR: Duration of Intracranial Response (DOIR)	—	—	8.8 Months Interval 3.0 to 14.3	—	—	—

SECONDARY outcome

Timeframe: Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 36 Months)

Percentage of participants with BOIR of CR, PR, or SD: IDCR, as defined by RANO-BM is reported. CR is measurable target lesions, the disappearance of all central nervous system CNS target lesions for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically. PR is at least a 30% decrease in the sum LD of CNS target lesions, taking as reference the baseline sum LD for at least 4 weeks; no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. Nontarget lesions requires disappearance CNS non-target lesions and no new CNS lesions. SD is less than (\<)30% decrease relative to baseline but \<20% increase in sum LD relative to nadir. PD is greater than or equal to (≥) 20% increase in sum LD relative to nadir and a relative increase of 20%, ≥1 lesion must increase by absolute value of ≥5 mm.

Outcome measures

Outcome measures
Measure	Part E Abemaciclib: Melanoma n=22 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part A 150 mg Abemaciclib: HR+, HER2+ Breast Cancer n=23 Participants Participants with HR+, HER2+ breast cancer received 150 mg abemaciclib orally once every 12 hours on days 1-21 of a 21-day cycle.	Part B 200 mg Abemaciclib: HR+, HER2- Breast Cancer n=52 Participants Participants with HR+, HER2- breast cancer received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.	Part D Abemaciclib: NSCLC n=23 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants with NSCLC receiving concurrent gemcitabine or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part E 200 mg Abemaciclib: Melanoma Participants with melanoma received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.	Part F 200 mg Abemaciclib: HR+ Breast Cancer, NSCLC, Melanoma Participants with HR+ (either HER2+ or HER2-) breast cancer, NSCLC, or melanoma and leptomeningeal metastases received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.
Percentage of Participants With Best Overall Intracranial Response (BOIR) of CR, PR, or SD: Intracranial Disease Control Rate (IDCR)	31.8 percentage of participants	52.2 percentage of participants	71.2 percentage of participants	43.5 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 36 Months)

ICBR is the percentage of participants with BOIR of CR, PR, or SD with duration of SD for at least 6 months, as defined by RANO-BM. CR is measurable target lesions, the disappearance of all CNS target lesions for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically. PR is at least a 30% decrease in the sum LD of CNS target lesions, taking as reference the baseline sum LD for at least 4 weeks; no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. SD is \<30% decrease relative to baseline but \<20% increase in sum LD relative to nadir. PD is greater than or equal to (≥) 20% increase in sum LD relative to nadir and a relative increase of 20%, ≥1 lesion must increase by absolute value of ≥5 mm.

Outcome measures

Outcome measures
Measure	Part E Abemaciclib: Melanoma n=22 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part A 150 mg Abemaciclib: HR+, HER2+ Breast Cancer n=23 Participants Participants with HR+, HER2+ breast cancer received 150 mg abemaciclib orally once every 12 hours on days 1-21 of a 21-day cycle.	Part B 200 mg Abemaciclib: HR+, HER2- Breast Cancer n=52 Participants Participants with HR+, HER2- breast cancer received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.	Part D Abemaciclib: NSCLC n=23 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants with NSCLC receiving concurrent gemcitabine or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part E 200 mg Abemaciclib: Melanoma Participants with melanoma received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.	Part F 200 mg Abemaciclib: HR+ Breast Cancer, NSCLC, Melanoma Participants with HR+ (either HER2+ or HER2-) breast cancer, NSCLC, or melanoma and leptomeningeal metastases received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.
Percentage of Participants With BOIR of CR, PR, or SD With Duration of SD for at Least 6 Months: Intracranial Clinical Benefit Rate (ICBR)	9.1 percentage of participants	13.0 percentage of participants	26.9 percentage of participants	26.1 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline to the Date of Death from Any Cause (Up to 5 Years)

Population: All participants who received at least one dose of study drug. Parts C and F were exploratory per protocol. Censored participants in Part A = 4, Part B = 20, Part D = 4, Part E = 4.

OS was measured from baseline to the date of death from any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for a particular analysis, OS was censored for that analysis at the date of last contact prior to the data inclusion cutoff date (contacts considered in the determination of last contact date include adverse event (AE) date, tumor assessment date, visit date, and last known alive date). OS was summarized using Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Part E Abemaciclib: Melanoma n=23 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part A 150 mg Abemaciclib: HR+, HER2+ Breast Cancer n=27 Participants Participants with HR+, HER2+ breast cancer received 150 mg abemaciclib orally once every 12 hours on days 1-21 of a 21-day cycle.	Part B 200 mg Abemaciclib: HR+, HER2- Breast Cancer n=58 Participants Participants with HR+, HER2- breast cancer received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.	Part D Abemaciclib: NSCLC n=28 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants with NSCLC receiving concurrent gemcitabine or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part E 200 mg Abemaciclib: Melanoma Participants with melanoma received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.	Part F 200 mg Abemaciclib: HR+ Breast Cancer, NSCLC, Melanoma Participants with HR+ (either HER2+ or HER2-) breast cancer, NSCLC, or melanoma and leptomeningeal metastases received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.
Overall Survival (OS)	2.93 months Interval 1.22 to 4.31	10.06 months Interval 4.21 to 14.3	13.38 months Interval 9.6 to 20.84	7.13 months Interval 3.65 to 9.37	—	—

SECONDARY outcome

Timeframe: Baseline to Disease Progression (Up to 36 Months)

Population: All participants who received at least one dose of study drug. Parts C and F were exploratory per protocol.

The percentage of participants with a best response of CR or PR objective response rate is complete response (CR) + partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1) guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. PD is defined as at least a 20% increase in the sum LD of CNS target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) and the 20% increase must be at least one lesion must increase by an absolute value of ≥5 mm to be considered progression.

Outcome measures

Outcome measures
Measure	Part E Abemaciclib: Melanoma n=23 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part A 150 mg Abemaciclib: HR+, HER2+ Breast Cancer n=27 Participants Participants with HR+, HER2+ breast cancer received 150 mg abemaciclib orally once every 12 hours on days 1-21 of a 21-day cycle.	Part B 200 mg Abemaciclib: HR+, HER2- Breast Cancer n=58 Participants Participants with HR+, HER2- breast cancer received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.	Part D Abemaciclib: NSCLC n=28 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants with NSCLC receiving concurrent gemcitabine or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part E 200 mg Abemaciclib: Melanoma Participants with melanoma received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.	Part F 200 mg Abemaciclib: HR+ Breast Cancer, NSCLC, Melanoma Participants with HR+ (either HER2+ or HER2-) breast cancer, NSCLC, or melanoma and leptomeningeal metastases received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.
Percentage of Participants With a Best Response of CR or PR: Extracranial Objective Response Rate (EORR)	0 percentage of participants	0 percentage of participants	1.7 percentage of participants	3.6 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 36 Months)

Population: All participants who received at least one dose of study drug. Parts C and F were exploratory per protocol.

Disease control rate (DCR) (CR+ PR+ SD) per RECIST v1.1. is defined as the percentage of participants with best overall response of CR, PR, or SD. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. PD is defined as at least a 20% increase in the sum LD of CNS target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) and the 20% increase must be at least one lesion must increase by an absolute value of ≥5 mm to be considered progression.

Outcome measures

Outcome measures
Measure	Part E Abemaciclib: Melanoma n=23 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part A 150 mg Abemaciclib: HR+, HER2+ Breast Cancer n=27 Participants Participants with HR+, HER2+ breast cancer received 150 mg abemaciclib orally once every 12 hours on days 1-21 of a 21-day cycle.	Part B 200 mg Abemaciclib: HR+, HER2- Breast Cancer n=58 Participants Participants with HR+, HER2- breast cancer received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.	Part D Abemaciclib: NSCLC n=28 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants with NSCLC receiving concurrent gemcitabine or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part E 200 mg Abemaciclib: Melanoma Participants with melanoma received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.	Part F 200 mg Abemaciclib: HR+ Breast Cancer, NSCLC, Melanoma Participants with HR+ (either HER2+ or HER2-) breast cancer, NSCLC, or melanoma and leptomeningeal metastases received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.
Percentage of Participants With a Best Overall Response of CR, PR, or SD: Extracranial Disease Control Rate (EDCR)	26.1 percentage of participants	40.7 percentage of participants	51.7 percentage of participants	39.3 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline to Objective Disease Progression or Death from Any Cause (Up to 36 Months)

Population: All participants who received at least one dose of study drug. Censored participants Part A = 1, Part B =2, Part D = 1 and Part E = 1. Parts C and F were exploratory per protocol.

PFS was measured from baseline to objective progression (intracranial or extracranial) as defined by (RANO-BM.) or death from any cause. Participants who have neither progressed nor died were censored at the day of their last radiographic tumor assessment. PD is greater than or equal to (≥) 20% increase in sum LD relative to nadir and a relative increase of 20%, ≥1 lesion must increase by absolute value of ≥5 mm. PFS was summarized using Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Part E Abemaciclib: Melanoma n=23 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part A 150 mg Abemaciclib: HR+, HER2+ Breast Cancer n=27 Participants Participants with HR+, HER2+ breast cancer received 150 mg abemaciclib orally once every 12 hours on days 1-21 of a 21-day cycle.	Part B 200 mg Abemaciclib: HR+, HER2- Breast Cancer n=58 Participants Participants with HR+, HER2- breast cancer received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.	Part D Abemaciclib: NSCLC n=28 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants with NSCLC receiving concurrent gemcitabine or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part E 200 mg Abemaciclib: Melanoma Participants with melanoma received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.	Part F 200 mg Abemaciclib: HR+ Breast Cancer, NSCLC, Melanoma Participants with HR+ (either HER2+ or HER2-) breast cancer, NSCLC, or melanoma and leptomeningeal metastases received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.
Progression Free Survival (PFS) Bi-compartmental	1.22 Months Interval 1.02 to 1.55	2.07 Months Interval 1.35 to 3.32	4.41 Months Interval 2.6 to 5.46	1.45 Months Interval 1.35 to 2.76	—	—

SECONDARY outcome

Timeframe: Baseline, Cycle 3 (Up to 63 Days)

Population: All participants who received at least one dose of study drug and had at least 1 baseline and an evaluable post baseline assessment. Parts C and F were exploratory per protocol.

The MDASI-BT is an instrument to assess multi-symptoms in participants with brain tumor metastases (including those with brain metastases secondary to breast cancer). The MDASI-BT of participants with a change from baseline is reported as mean core symptoms, mean brain tumor symptoms, and symptom groupings (mean focal neurologic deficit, mean generalized/disease status symptoms, and mean gastrointestinal symptoms). The mean of all symptom subscale items was calculated where 0 equals "not present" and 10 equals "as bad as you can imagine." A change from baseline with negative values indicate improvement, positive values indicate worsening.

Outcome measures

Outcome measures
Measure	Part E Abemaciclib: Melanoma n=7 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part A 150 mg Abemaciclib: HR+, HER2+ Breast Cancer n=11 Participants Participants with HR+, HER2+ breast cancer received 150 mg abemaciclib orally once every 12 hours on days 1-21 of a 21-day cycle.	Part B 200 mg Abemaciclib: HR+, HER2- Breast Cancer n=35 Participants Participants with HR+, HER2- breast cancer received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.	Part D Abemaciclib: NSCLC n=10 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants with NSCLC receiving concurrent gemcitabine or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part E 200 mg Abemaciclib: Melanoma Participants with melanoma received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.	Part F 200 mg Abemaciclib: HR+ Breast Cancer, NSCLC, Melanoma Participants with HR+ (either HER2+ or HER2-) breast cancer, NSCLC, or melanoma and leptomeningeal metastases received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.
Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale mean core symptom severity	-0.53 units on a scale Standard Deviation 0.62	-0.98 units on a scale Standard Deviation 0.86	-0.17 units on a scale Standard Deviation 0.99	-0.38 units on a scale Standard Deviation 1.19	—	—
Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale mean brain tumor symptom severity	0.31 units on a scale Standard Deviation 1.11	-0.47 units on a scale Standard Deviation 0.57	-0.29 units on a scale Standard Deviation 1.05	-0.10 units on a scale Standard Deviation 1.22	—	—
Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale mean focal neurologic deficit symptom severity	0.54 units on a scale Standard Deviation 1.16	-0.84 units on a scale Standard Deviation 0.92	-0.36 units on a scale Standard Deviation 1.23	-0.44 units on a scale Standard Deviation 0.58	—	—
Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale mean generalized disease status	0.01 units on a scale Standard Deviation 0.89	-0.47 units on a scale Standard Deviation 1.03	0 units on a scale Standard Deviation 1.39	0.28 units on a scale Standard Deviation 1.51	—	—
Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale mean gastrointestinal symptom	0 units on a scale Standard Deviation 0.29	-1.35 units on a scale Standard Deviation 2.11	0.40 units on a scale Standard Deviation 1.91	1.00 units on a scale Standard Deviation 1.46	—	—

SECONDARY outcome

Timeframe: Parts A, B, D, E, F, Cycle 3, Day 1: Predose; Part C, Cycle 4, Day 1: Predose

Population: All participants who had evaluable PK data.

A PK plasma sample was taken prior to abemaciclib dose to analyze the minimum concentrations of abemaciclib and its metabolites (Cmin) - Individual Cmin values were averaged if there were 3 or more available data points, otherwise individual data are reported.

Outcome measures

Outcome measures
Measure	Part E Abemaciclib: Melanoma n=5 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part A 150 mg Abemaciclib: HR+, HER2+ Breast Cancer n=3 Participants Participants with HR+, HER2+ breast cancer received 150 mg abemaciclib orally once every 12 hours on days 1-21 of a 21-day cycle.	Part B 200 mg Abemaciclib: HR+, HER2- Breast Cancer n=12 Participants Participants with HR+, HER2- breast cancer received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.	Part D Abemaciclib: NSCLC n=1 Participants Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants with NSCLC receiving concurrent gemcitabine or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part E 200 mg Abemaciclib: Melanoma n=2 Participants Participants with melanoma received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.	Part F 200 mg Abemaciclib: HR+ Breast Cancer, NSCLC, Melanoma n=4 Participants Participants with HR+ (either HER2+ or HER2-) breast cancer, NSCLC, or melanoma and leptomeningeal metastases received 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21-day cycle.
Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) LSN2839567 (M2)	100 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 77.5	72.6 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 8.23	77.3 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 121	NA nanogram/milliliter (ng/mL) Geometric Coefficient of Variation NA N=1, Geometric mean and CV were not calculated. Individual value reported: 98.8 ng/mL	NA nanogram/milliliter (ng/mL) Geometric Coefficient of Variation NA N=2, Geometric mean and CV were not calculated. Individual values reported: 61.6 ng/mL and 90.7 ng/mL	68.5 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 150
Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) LSN3106726 (M20)	203 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 43.3	158 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 25.0	133 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 160	NA nanogram/milliliter (ng/mL) Geometric Coefficient of Variation NA N=1, Geometric mean and CV were not calculated. Individual value reported: 181 ng/mL	NA nanogram/milliliter (ng/mL) Geometric Coefficient of Variation NA N=2, Geometric mean and CV were not calculated. Individual values reported: 109 ng/mL and 172 ng/mL	122 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 137
Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) LSN3106729 (M18)	28.9 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 108	36.8 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 39.3	42.4 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 85.6	NA nanogram/milliliter (ng/mL) Geometric Coefficient of Variation NA N=1, Geometric mean and CV were not calculated. Individual value reported: 28.2 ng/mL	NA nanogram/milliliter (ng/mL) Geometric Coefficient of Variation NA N=2, Geometric mean and CV were not calculated. Individual values reported: 22.2 ng/mL and 44.2 ng/mL	27.0 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 242
Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) Abemaciclib	306 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 33.5	133 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 13.4	120 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 186	NA nanogram/milliliter (ng/mL) Geometric Coefficient of Variation NA N=1, Geometric mean and coefficient of variation (CV) were not calculated. Individual value reported: 256 ng/mL	NA nanogram/milliliter (ng/mL) Geometric Coefficient of Variation NA N=2, Geometric mean and CV were not calculated. Individual values reported: 99.7 ng/mL and 222 ng/mL	142 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 80.0

Adverse Events

Part A Abemaciclib: HR+, HER2+ Breast Cancer

Serious events: 6 serious events

Other events: 23 other events

Deaths: 23 deaths

Part B Abemaciclib: HR+, HER2- Breast Cancer

Serious events: 16 serious events

Other events: 55 other events

Deaths: 38 deaths

Part C Abemaciclib: Surgical Resection

Serious events: 3 serious events

Other events: 8 other events

Deaths: 6 deaths

Part D Abemaciclib: NSCLC

Serious events: 8 serious events

Other events: 27 other events

Deaths: 24 deaths

Part E Abemaciclib: Melanoma

Serious events: 4 serious events

Other events: 16 other events

Deaths: 19 deaths

Part F: Abemaciclib HR+ Breast Cancer, NSCLC, or Melanoma

Serious events: 7 serious events

Other events: 16 other events

Deaths: 12 deaths

Serious adverse events

Serious adverse events
Measure	Part A Abemaciclib: HR+, HER2+ Breast Cancer n=27 participants at risk Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or in combination with Endocrine Therapy (ET). Participants with hormone receptor positive HR+, HER2+ breast cancer receiving concurrent trastuzumab, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part B Abemaciclib: HR+, HER2- Breast Cancer n=58 participants at risk Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or in combination with Endocrine Therapy (ET). Participants may continue to receive treatment until discontinuation criteria are met.	Part C Abemaciclib: Surgical Resection n=9 participants at risk Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for participants with breast cancer in combination with Endocrine Therapy (ET). Participants with HR+, HER2+ breast cancer, NSCLC, or melanoma with intracranial lesions for which surgical resection is clinically indicated receiving concurrent trastuzumab, gemcitabine, or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours for 5-14 days prior to surgical resection. Dosing may resume following wound healing on a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part D Abemaciclib: NSCLC n=28 participants at risk Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants with NSCLC receiving concurrent gemcitabine or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part E Abemaciclib: Melanoma n=23 participants at risk Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part F: Abemaciclib HR+ Breast Cancer, NSCLC, or Melanoma n=17 participants at risk Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for participants with breast cancer in combination with Endocrine Therapy (ET). Participants with HR+ (either HER2+ or HER2-) breast cancer, NSCLC, or melanoma and leptomeningeal metastases received concurrent trastuzumab, gemcitabine, or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Blood and lymphatic system disorders Anaemia	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Cardiac disorders Acute coronary syndrome	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Cardiac disorders Cardiac failure	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Cardiac disorders Myocardial infarction	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Eye disorders Glaucoma	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	7.4% 2/27 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	3.4% 2/58 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Enterocolitis	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Pancreatitis	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.
General disorders General physical health deterioration	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
General disorders Pain	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.
General disorders Pyrexia	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	3.4% 2/58 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Hepatobiliary disorders Hepatocellular injury	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Hepatobiliary disorders Jaundice cholestatic	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Infections and infestations Lung infection	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	10.7% 3/28 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Infections and infestations Sepsis	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Infections and infestations Shunt infection	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Infections and infestations Skin infection	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Fracture	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Dehydration	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	8.7% 2/23 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Nervous system disorders Aphasia	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Nervous system disorders Ataxia	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Nervous system disorders Brain oedema	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Nervous system disorders Headache	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Nervous system disorders Seizure	7.4% 2/27 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	11.8% 2/17 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.
Nervous system disorders Syncope	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Psychiatric disorders Confusional state	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Psychiatric disorders Mental status changes	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Renal and urinary disorders Acute kidney injury	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Renal and urinary disorders Chronic kidney disease	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Renal and urinary disorders Renal failure	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Vascular disorders Embolism	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	3.4% 2/58 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Vascular disorders Shock haemorrhagic	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.

Other adverse events

Other adverse events
Measure	Part A Abemaciclib: HR+, HER2+ Breast Cancer n=27 participants at risk Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or in combination with Endocrine Therapy (ET). Participants with hormone receptor positive HR+, HER2+ breast cancer receiving concurrent trastuzumab, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part B Abemaciclib: HR+, HER2- Breast Cancer n=58 participants at risk Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or in combination with Endocrine Therapy (ET). Participants may continue to receive treatment until discontinuation criteria are met.	Part C Abemaciclib: Surgical Resection n=9 participants at risk Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for participants with breast cancer in combination with Endocrine Therapy (ET). Participants with HR+, HER2+ breast cancer, NSCLC, or melanoma with intracranial lesions for which surgical resection is clinically indicated receiving concurrent trastuzumab, gemcitabine, or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours for 5-14 days prior to surgical resection. Dosing may resume following wound healing on a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part D Abemaciclib: NSCLC n=28 participants at risk Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants with NSCLC receiving concurrent gemcitabine or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part E Abemaciclib: Melanoma n=23 participants at risk Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Part F: Abemaciclib HR+ Breast Cancer, NSCLC, or Melanoma n=17 participants at risk Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for participants with breast cancer in combination with Endocrine Therapy (ET). Participants with HR+ (either HER2+ or HER2-) breast cancer, NSCLC, or melanoma and leptomeningeal metastases received concurrent trastuzumab, gemcitabine, or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
General disorders Chills	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	22.2% 2/9 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Anaemia	11.1% 3/27 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	20.7% 12/58 • Number of events 14 • Up to 36 Months All participants who received at least one dose of study drug.	44.4% 4/9 • Number of events 7 • Up to 36 Months All participants who received at least one dose of study drug.	17.9% 5/28 • Number of events 6 • Up to 36 Months All participants who received at least one dose of study drug.	8.7% 2/23 • Number of events 5 • Up to 36 Months All participants who received at least one dose of study drug.	29.4% 5/17 • Number of events 5 • Up to 36 Months All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Haemorrhagic diathesis	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Leukopenia	7.4% 2/27 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	12.1% 7/58 • Number of events 10 • Up to 36 Months All participants who received at least one dose of study drug.	44.4% 4/9 • Number of events 6 • Up to 36 Months All participants who received at least one dose of study drug.	14.3% 4/28 • Number of events 6 • Up to 36 Months All participants who received at least one dose of study drug.	13.0% 3/23 • Number of events 5 • Up to 36 Months All participants who received at least one dose of study drug.	17.6% 3/17 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Lymphopenia	14.8% 4/27 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.	10.3% 6/58 • Number of events 9 • Up to 36 Months All participants who received at least one dose of study drug.	33.3% 3/9 • Number of events 8 • Up to 36 Months All participants who received at least one dose of study drug.	14.3% 4/28 • Number of events 7 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	17.6% 3/17 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Neutropenia	22.2% 6/27 • Number of events 8 • Up to 36 Months All participants who received at least one dose of study drug.	29.3% 17/58 • Number of events 32 • Up to 36 Months All participants who received at least one dose of study drug.	44.4% 4/9 • Number of events 6 • Up to 36 Months All participants who received at least one dose of study drug.	25.0% 7/28 • Number of events 9 • Up to 36 Months All participants who received at least one dose of study drug.	21.7% 5/23 • Number of events 8 • Up to 36 Months All participants who received at least one dose of study drug.	11.8% 2/17 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	14.8% 4/27 • Number of events 5 • Up to 36 Months All participants who received at least one dose of study drug.	19.0% 11/58 • Number of events 12 • Up to 36 Months All participants who received at least one dose of study drug.	44.4% 4/9 • Number of events 5 • Up to 36 Months All participants who received at least one dose of study drug.	28.6% 8/28 • Number of events 11 • Up to 36 Months All participants who received at least one dose of study drug.	13.0% 3/23 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.	17.6% 3/17 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.
Cardiac disorders Palpitations	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Ear and labyrinth disorders Hypoacusis	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	3.4% 2/58 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Eye disorders Diplopia	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Eye disorders Eye pain	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Eye disorders Photopsia	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Eye disorders Vision blurred	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	5.2% 3/58 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	10.7% 3/28 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	11.8% 2/17 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal distension	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	11.8% 2/17 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	11.1% 3/27 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	15.5% 9/58 • Number of events 14 • Up to 36 Months All participants who received at least one dose of study drug.	22.2% 2/9 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.	7.1% 2/28 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	21.7% 5/23 • Number of events 5 • Up to 36 Months All participants who received at least one dose of study drug.	23.5% 4/17 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Anal incontinence	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Ascites	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	7.4% 2/27 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	15.5% 9/58 • Number of events 11 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	25.0% 7/28 • Number of events 7 • Up to 36 Months All participants who received at least one dose of study drug.	8.7% 2/23 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	17.6% 3/17 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	55.6% 15/27 • Number of events 26 • Up to 36 Months All participants who received at least one dose of study drug.	77.6% 45/58 • Number of events 100 • Up to 36 Months All participants who received at least one dose of study drug.	44.4% 4/9 • Number of events 6 • Up to 36 Months All participants who received at least one dose of study drug.	53.6% 15/28 • Number of events 21 • Up to 36 Months All participants who received at least one dose of study drug.	21.7% 5/23 • Number of events 6 • Up to 36 Months All participants who received at least one dose of study drug.	35.3% 6/17 • Number of events 6 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Dry mouth	7.4% 2/27 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	6.9% 4/58 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	7.1% 2/28 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Dysphagia	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Gastritis	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Gastrooesophageal reflux disease	7.4% 2/27 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	8.6% 5/58 • Number of events 5 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Haemorrhoids	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	33.3% 9/27 • Number of events 11 • Up to 36 Months All participants who received at least one dose of study drug.	44.8% 26/58 • Number of events 32 • Up to 36 Months All participants who received at least one dose of study drug.	22.2% 2/9 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	28.6% 8/28 • Number of events 10 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	41.2% 7/17 • Number of events 10 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Oral pain	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Stomatitis	7.4% 2/27 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	25.9% 7/27 • Number of events 8 • Up to 36 Months All participants who received at least one dose of study drug.	34.5% 20/58 • Number of events 31 • Up to 36 Months All participants who received at least one dose of study drug.	22.2% 2/9 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	14.3% 4/28 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	29.4% 5/17 • Number of events 6 • Up to 36 Months All participants who received at least one dose of study drug.
General disorders Fatigue	33.3% 9/27 • Number of events 9 • Up to 36 Months All participants who received at least one dose of study drug.	48.3% 28/58 • Number of events 31 • Up to 36 Months All participants who received at least one dose of study drug.	22.2% 2/9 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	39.3% 11/28 • Number of events 16 • Up to 36 Months All participants who received at least one dose of study drug.	17.4% 4/23 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.	52.9% 9/17 • Number of events 9 • Up to 36 Months All participants who received at least one dose of study drug.
General disorders Gait disturbance	11.1% 3/27 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	6.9% 4/58 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
General disorders General physical health deterioration	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	8.7% 2/23 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
General disorders Influenza like illness	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	5.2% 3/58 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
General disorders Localised oedema	11.1% 3/27 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	5.2% 3/58 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
General disorders Malaise	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	3.4% 2/58 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
General disorders Non-cardiac chest pain	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	5.2% 3/58 • Number of events 5 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
General disorders Oedema peripheral	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	5.2% 3/58 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	13.0% 3/23 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
General disorders Pain	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	11.8% 2/17 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.
General disorders Pyrexia	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	5.2% 3/58 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	7.1% 2/28 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Infections and infestations Ear infection	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Infections and infestations Sinusitis	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	5.2% 3/58 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	7.1% 2/28 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	5.2% 3/58 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Contusion	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Fall	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	6.9% 4/58 • Number of events 6 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	10.7% 3/28 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Fracture	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Incision site pain	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Skin laceration	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Vascular access complication	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	7.1% 2/28 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Investigations Alanine aminotransferase increased	11.1% 3/27 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	6.9% 4/58 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.	66.7% 6/9 • Number of events 7 • Up to 36 Months All participants who received at least one dose of study drug.	7.1% 2/28 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.	8.7% 2/23 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	11.8% 2/17 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.
Investigations Aspartate aminotransferase increased	14.8% 4/27 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.	3.4% 2/58 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	33.3% 3/9 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	7.1% 2/28 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	17.4% 4/23 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.	11.8% 2/17 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.
Investigations Blood alkaline phosphatase increased	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	33.3% 3/9 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.	7.1% 2/28 • Number of events 5 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Investigations Blood bilirubin increased	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Investigations Blood creatinine increased	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	8.6% 5/58 • Number of events 6 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	7.1% 2/28 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.	8.7% 2/23 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.
Investigations Haemoglobin increased	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Investigations International normalised ratio increased	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Investigations Weight decreased	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	10.3% 6/58 • Number of events 6 • Up to 36 Months All participants who received at least one dose of study drug.	22.2% 2/9 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	14.3% 4/28 • Number of events 5 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	11.8% 2/17 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.
Investigations Weight increased	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	3.4% 2/58 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	11.8% 2/17 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	11.1% 3/27 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.	32.8% 19/58 • Number of events 19 • Up to 36 Months All participants who received at least one dose of study drug.	22.2% 2/9 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	25.0% 7/28 • Number of events 10 • Up to 36 Months All participants who received at least one dose of study drug.	8.7% 2/23 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	11.8% 2/17 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Dehydration	11.1% 3/27 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	10.3% 6/58 • Number of events 6 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	10.7% 3/28 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	7.1% 2/28 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	33.3% 3/9 • Number of events 9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypermagnesaemia	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypernatraemia	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypoalbuminaemia	3.7% 1/27 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	11.8% 2/17 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypocalcaemia	7.4% 2/27 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	44.4% 4/9 • Number of events 5 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	17.6% 3/17 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	14.8% 4/27 • Number of events 7 • Up to 36 Months All participants who received at least one dose of study drug.	19.0% 11/58 • Number of events 17 • Up to 36 Months All participants who received at least one dose of study drug.	22.2% 2/9 • Number of events 5 • Up to 36 Months All participants who received at least one dose of study drug.	7.1% 2/28 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	11.8% 2/17 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	11.1% 3/27 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	22.2% 2/9 • Number of events 9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	17.6% 3/17 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	5.2% 3/58 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	5.2% 3/58 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	10.7% 3/28 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	5.2% 3/58 • Number of events 7 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	8.7% 2/23 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	3.4% 2/58 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	8.6% 5/58 • Number of events 5 • Up to 36 Months All participants who received at least one dose of study drug.	22.2% 2/9 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Muscular weakness	25.9% 7/27 • Number of events 8 • Up to 36 Months All participants who received at least one dose of study drug.	6.9% 4/58 • Number of events 5 • Up to 36 Months All participants who received at least one dose of study drug.	22.2% 2/9 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	7.1% 2/28 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	8.7% 2/23 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	23.5% 4/17 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	6.9% 4/58 • Number of events 5 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	13.0% 3/23 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	8.6% 5/58 • Number of events 5 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	13.0% 3/23 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Nervous system disorders Amnesia	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Nervous system disorders Aphasia	7.4% 2/27 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	5.2% 3/58 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Nervous system disorders Balance disorder	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Nervous system disorders Cognitive disorder	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	22.2% 2/9 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Nervous system disorders Disturbance in attention	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Nervous system disorders Dizziness	7.4% 2/27 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	13.8% 8/58 • Number of events 8 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Nervous system disorders Dysarthria	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	7.1% 2/28 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Nervous system disorders Dysgeusia	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	3.4% 2/58 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	22.2% 2/9 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Nervous system disorders Headache	7.4% 2/27 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	24.1% 14/58 • Number of events 23 • Up to 36 Months All participants who received at least one dose of study drug.	22.2% 2/9 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	14.3% 4/28 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.	8.7% 2/23 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	17.6% 3/17 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.
Nervous system disorders Hemiparesis	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Nervous system disorders Neuropathy	11.1% 3/27 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	20.7% 12/58 • Number of events 19 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Nervous system disorders Peripheral motor neuropathy	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	3.4% 2/58 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Nervous system disorders Presyncope	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Nervous system disorders Seizure	14.8% 4/27 • Number of events 5 • Up to 36 Months All participants who received at least one dose of study drug.	5.2% 3/58 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	13.0% 3/23 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Nervous system disorders Somnolence	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Nervous system disorders Tremor	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	5.2% 3/58 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Psychiatric disorders Agitation	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	8.7% 2/23 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Psychiatric disorders Anxiety	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	5.2% 3/58 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	7.1% 2/28 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Psychiatric disorders Confusional state	7.4% 2/27 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	22.2% 2/9 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	17.9% 5/28 • Number of events 8 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Psychiatric disorders Depression	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	6.9% 4/58 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Psychiatric disorders Insomnia	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	5.2% 3/58 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Renal and urinary disorders Acute kidney injury	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	3.4% 2/58 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	7.1% 2/28 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Renal and urinary disorders Cystitis noninfective	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	5.2% 3/58 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Renal and urinary disorders Urinary incontinence	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Renal and urinary disorders Urinary retention	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Reproductive system and breast disorders Breast pain	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	8.6% 5/58 • Number of events 7 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	15.5% 9/58 • Number of events 9 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	17.9% 5/28 • Number of events 5 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	11.8% 2/17 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	3.7% 1/27 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	7.1% 2/28 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	1.7% 1/58 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Sinus pain	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Alopecia	7.4% 2/27 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	3.4% 2/58 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	11.1% 1/9 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Dry skin	7.4% 2/27 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	6.9% 4/58 • Number of events 5 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	7.1% 2/28 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	4.3% 1/23 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash	11.1% 3/27 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	5.2% 3/58 • Number of events 6 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Skin ulcer	7.4% 2/27 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/58 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Vascular disorders Embolism	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	5.2% 3/58 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.
Vascular disorders Hypertension	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	3.4% 2/58 • Number of events 4 • Up to 36 Months All participants who received at least one dose of study drug.	22.2% 2/9 • Number of events 3 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/28 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/17 • Up to 36 Months All participants who received at least one dose of study drug.
Vascular disorders Hypotension	0.00% 0/27 • Up to 36 Months All participants who received at least one dose of study drug.	3.4% 2/58 • Number of events 2 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/9 • Up to 36 Months All participants who received at least one dose of study drug.	3.6% 1/28 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.	0.00% 0/23 • Up to 36 Months All participants who received at least one dose of study drug.	5.9% 1/17 • Number of events 1 • Up to 36 Months All participants who received at least one dose of study drug.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: (800) 545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60