Trial Outcomes & Findings for Dose Escalation Study With MK-2206 in Patients With Locally Advanced or Metastatic Solid Tumors (MK-2206-002) (NCT NCT00670488)

Last Updated: 2019-04-01

Results Overview

DLT was any drug-related AE, regardless of grade, leading to a dose modification of MK-2206. Dose-limiting hematologic and nonhematologic toxicities were defined differently and were based on events occurring during the first cycle of study drug administration. Hematologic DLT defined as any Grade (Gr) 4 or greater hematologic toxicity except neutropenia described as follows: Neutropenia that was Gr 4 lasting for ≥7 days, or Gr 3/Gr 4 with fever \>38.5°C and/or infection requiring antibiotic or anti-fungal treatment considered DLT. Gr 4 thrombocytopenia (≤25.0 x 10\^9/L) was also considered DLT. Non-hematologic DLTs were defined as any Gr 3, 4, or 5 nonhematologic toxicity, with the specific exceptions of: Gr 3 nausea, vomiting, diarrhea, or dehydration occurring with inadequate supportive care and lasting \<48 hours; alopecia; inadequately treated hypersensitivity reactions; and Gr 3 elevated transaminases of ≤1 week in duration. A participant could have more than one DLT.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

104 participants

Primary outcome timeframe

Day 1 to Day 28 (Cycle 1)

Results posted on

2019-04-01

Participant Flow

A total of 104 participants were enrolled and received treatment in this study.

Participant milestones

Participant milestones
Measure	MK-2206 30 mg QOD Participants receive 30 mg oral MK-2206 every other day (QOD) in repeating 4-week treatment cycles.	MK-2206 60 mg QOD Participants receive 60 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 75 mg QOD Participants receive 75 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QOD Participants receive 90 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QW Participants receive 90 mg oral MK-2206 every week (QW) in repeating 4-week treatment cycles.	MK-2206 135 mg QW Participants receive 135 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 200 mg QW Participants receive 200 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 300 mg QW Participants receive 300 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 250 mg QW Participants receive 250 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 150 mg QW Participants receive 150 mg oral MK-2206 QW in repeating 4-week treatment cycles.
Overall Study STARTED	3	58	3	7	3	5	17	3	3	2
Overall Study COMPLETED	0	0	0	0	0	0	0	0	0	0
Overall Study NOT COMPLETED	3	58	3	7	3	5	17	3	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	MK-2206 30 mg QOD Participants receive 30 mg oral MK-2206 every other day (QOD) in repeating 4-week treatment cycles.	MK-2206 60 mg QOD Participants receive 60 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 75 mg QOD Participants receive 75 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QOD Participants receive 90 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QW Participants receive 90 mg oral MK-2206 every week (QW) in repeating 4-week treatment cycles.	MK-2206 135 mg QW Participants receive 135 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 200 mg QW Participants receive 200 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 300 mg QW Participants receive 300 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 250 mg QW Participants receive 250 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 150 mg QW Participants receive 150 mg oral MK-2206 QW in repeating 4-week treatment cycles.
Overall Study Adverse Event	0	7	0	3	1	1	5	1	0	1
Overall Study Physician Decision	1	9	0	1	0	0	0	0	0	0
Overall Study Progressive Disease	2	41	3	2	2	4	11	2	2	1
Overall Study Withdrawal by Subject	0	1	0	1	0	0	1	0	1	0

Baseline Characteristics

Dose Escalation Study With MK-2206 in Patients With Locally Advanced or Metastatic Solid Tumors (MK-2206-002)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MK-2206 30 mg QOD n=3 Participants Participants receive 30 mg oral MK-2206 every other day (QOD) in repeating 4-week treatment cycles.	MK-2206 60 mg QOD n=58 Participants Participants receive 60 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 75 mg QOD n=3 Participants Participants receive 75 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QOD n=7 Participants Participants receive 90 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QW n=3 Participants Participants receive 90 mg oral MK-2206 every week (QW) in repeating 4-week treatment cycles.	MK-2206 135 mg QW n=5 Participants Participants receive 135 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 200 mg QW n=17 Participants Participants receive 200 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 300 mg QW n=3 Participants Participants receive 300 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 250 mg QW n=3 Participants Participants receive 250 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 150 mg QW n=2 Participants Participants receive 150 mg oral MK-2206 QW in repeating 4-week treatment cycles.	Total n=104 Participants Total of all reporting groups
Age, Continuous	60.3 Years STANDARD_DEVIATION 9.5 • n=5 Participants	58.2 Years STANDARD_DEVIATION 11.4 • n=7 Participants	62.3 Years STANDARD_DEVIATION 7.6 • n=5 Participants	58.0 Years STANDARD_DEVIATION 13.1 • n=4 Participants	59.0 Years STANDARD_DEVIATION 8.2 • n=21 Participants	53.8 Years STANDARD_DEVIATION 8.8 • n=8 Participants	57.9 Years STANDARD_DEVIATION 13.3 • n=8 Participants	58.7 Years STANDARD_DEVIATION 8.4 • n=24 Participants	57.0 Years STANDARD_DEVIATION 5.6 • n=42 Participants	56.0 Years STANDARD_DEVIATION 18.4 • n=42 Participants	58.1 Years STANDARD_DEVIATION 11.1 • n=42 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	28 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants	0 Participants n=21 Participants	4 Participants n=8 Participants	7 Participants n=8 Participants	2 Participants n=24 Participants	1 Participants n=42 Participants	1 Participants n=42 Participants	49 Participants n=42 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	30 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	1 Participants n=8 Participants	10 Participants n=8 Participants	1 Participants n=24 Participants	2 Participants n=42 Participants	1 Participants n=42 Participants	55 Participants n=42 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 28 (Cycle 1)

Population: The All Participants as Treated (APaT) population: All participants who received at least one dose of study treatment.

Outcome measures

Outcome measures
Measure	MK-2206 30 mg QOD n=3 Participants Participants receive 30 mg oral MK-2206 every other day (QOD) in repeating 4-week treatment cycles.	MK-2206 60 mg QOD n=58 Participants Participants receive 60 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 75 mg QOD n=3 Participants Participants receive 75 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QOD n=7 Participants Participants receive 90 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QW n=3 Participants Participants receive 90 mg oral MK-2206 every week (QW) in repeating 4-week treatment cycles.	MK-2206 135 mg QW n=5 Participants Participants receive 135 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 200 mg QW n=17 Participants Participants receive 200 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 300 mg QW n=3 Participants Participants receive 300 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 250 mg QW n=3 Participants Participants receive 250 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 150 mg QW n=2 Participants Participants receive 150 mg oral MK-2206 QW in repeating 4-week treatment cycles.
Number of Participants With Dose Limiting Toxicities (DLTs) Stomatitis	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Dose Limiting Toxicities (DLTs) Diarrhoea	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Dose Limiting Toxicities (DLTs) Dermatitis acneiform	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Dose Limiting Toxicities (DLTs) Rash	0 Participants	5 Participants	2 Participants	3 Participants	0 Participants	0 Participants	3 Participants	2 Participants	2 Participants	1 Participants
Number of Participants With Dose Limiting Toxicities (DLTs) Hyperglycaemia	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Dose Limiting Toxicities (DLTs) Rash macular	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Dose Limiting Toxicities (DLTs) Pruritis	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Dose Limiting Toxicities (DLTs) Rash generalized	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Dose Limiting Toxicities (DLTs) Total number of participants with DLTs	0 Participants	8 Participants	3 Participants	4 Participants	0 Participants	0 Participants	4 Participants	3 Participants	2 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to 269 days

Population: APaT population: All participants who received at least one dose of study treatment.

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which was temporally associated with the use of the SPONSOR's product, was also an AE. The number of participants that experienced one or more AEs was reported for each dose level group.

Outcome measures

Outcome measures
Measure	MK-2206 30 mg QOD n=3 Participants Participants receive 30 mg oral MK-2206 every other day (QOD) in repeating 4-week treatment cycles.	MK-2206 60 mg QOD n=58 Participants Participants receive 60 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 75 mg QOD n=3 Participants Participants receive 75 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QOD n=7 Participants Participants receive 90 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QW n=3 Participants Participants receive 90 mg oral MK-2206 every week (QW) in repeating 4-week treatment cycles.	MK-2206 135 mg QW n=5 Participants Participants receive 135 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 200 mg QW n=17 Participants Participants receive 200 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 300 mg QW n=3 Participants Participants receive 300 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 250 mg QW n=3 Participants Participants receive 250 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 150 mg QW n=2 Participants Participants receive 150 mg oral MK-2206 QW in repeating 4-week treatment cycles.
Number of Participants With One or More Adverse Events (AE)	3 Participants	58 Participants	3 Participants	7 Participants	3 Participants	5 Participants	17 Participants	3 Participants	3 Participants	2 Participants

PRIMARY outcome

Timeframe: Days 1 and 27: predose and 0.5, 1, 2, 3, 4, 6, 10, 24, and 48 hours after MK-2206 dosing

Population: All participants who received MK-2206 orally QOD during Cycle 1 (30, 60, 75, and 90 mg QOD) and had available PK data. Data for the MK-2206 QW dose groups (90, 135, 200, 300, 250, and 150 mg QW) are reported separately.

Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. AUC 0-48hr was calculated for Day 1 and the last day of treatment in Cycle 1 (Day 27) and reported for all dose levels receiving MK-2206 orally QOD (30, 60, 75, and 90 mg QOD).

Outcome measures

Outcome measures
Measure	MK-2206 30 mg QOD n=3 Participants Participants receive 30 mg oral MK-2206 every other day (QOD) in repeating 4-week treatment cycles.	MK-2206 60 mg QOD n=58 Participants Participants receive 60 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 75 mg QOD n=3 Participants Participants receive 75 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QOD n=7 Participants Participants receive 90 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QW Participants receive 90 mg oral MK-2206 every week (QW) in repeating 4-week treatment cycles.	MK-2206 135 mg QW Participants receive 135 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 200 mg QW Participants receive 200 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 300 mg QW Participants receive 300 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 250 mg QW Participants receive 250 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 150 mg QW Participants receive 150 mg oral MK-2206 QW in repeating 4-week treatment cycles.
Area Under the Concentration-time Curve of MK-2206 From Time 0 to 48 Hours (AUC0-48hr) in Participants Receiving Multiple QOD Dosing Day 1	916 nM•hr Standard Deviation 395	1950 nM•hr Standard Deviation 832	2110 nM•hr Standard Deviation 782	3950 nM•hr Standard Deviation 1920	—	—	—	—	—	—
Area Under the Concentration-time Curve of MK-2206 From Time 0 to 48 Hours (AUC0-48hr) in Participants Receiving Multiple QOD Dosing Last Day (Day 27)	NA nM•hr Standard Deviation NA AUC0-48 hr could not be determined due to insufficient data.	6160 nM•hr Standard Deviation 2690	NA nM•hr Standard Deviation NA AUC0-48 hr could not be determined due to insufficient data.	7970 nM•hr Standard Deviation 5990	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Days 1 and 27: predose and 0.5, 1, 2, 3, 4, 6, 10, 24, and 48 hours after MK-2206 dosing

Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. Cmax was calculated for Day 1 and the last day of treatment in Cycle 1 (Day 27) and reported for all dose levels receiving MK-2206 orally QOD (30, 60, 75, and 90 mg QOD).

Outcome measures

Outcome measures
Measure	MK-2206 30 mg QOD n=3 Participants Participants receive 30 mg oral MK-2206 every other day (QOD) in repeating 4-week treatment cycles.	MK-2206 60 mg QOD n=58 Participants Participants receive 60 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 75 mg QOD n=3 Participants Participants receive 75 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QOD n=7 Participants Participants receive 90 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QW Participants receive 90 mg oral MK-2206 every week (QW) in repeating 4-week treatment cycles.	MK-2206 135 mg QW Participants receive 135 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 200 mg QW Participants receive 200 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 300 mg QW Participants receive 300 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 250 mg QW Participants receive 250 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 150 mg QW Participants receive 150 mg oral MK-2206 QW in repeating 4-week treatment cycles.
Maximum Concentration (Cmax) of MK-2206 in Participants Receiving Multiple QOD Dosing Last Day (Day 27)	NA nM Standard Deviation NA Cmax could not be determined due to insufficient data.	176 nM Standard Deviation 77.9	NA nM Standard Deviation NA Cmax could not be determined due to insufficient data.	232 nM Standard Deviation 148	—	—	—	—	—	—
Maximum Concentration (Cmax) of MK-2206 in Participants Receiving Multiple QOD Dosing Day 1	33.7 nM Standard Deviation 15.8	71.6 nM Standard Deviation 36.3	102 nM Standard Deviation 79.9	132 nM Standard Deviation 76.5	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Days 1 and 27: predose and 48 hours after MK-2206 dosing.

Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. C48hr was calculated for Day 1 and the last day of treatment in Cycle 1 (Day 27) and reported for all dose levels receiving MK-2206 orally QOD (30, 60, 75, and 90 mg QOD).

Outcome measures

Outcome measures
Measure	MK-2206 30 mg QOD n=3 Participants Participants receive 30 mg oral MK-2206 every other day (QOD) in repeating 4-week treatment cycles.	MK-2206 60 mg QOD n=58 Participants Participants receive 60 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 75 mg QOD n=3 Participants Participants receive 75 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QOD n=7 Participants Participants receive 90 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QW Participants receive 90 mg oral MK-2206 every week (QW) in repeating 4-week treatment cycles.	MK-2206 135 mg QW Participants receive 135 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 200 mg QW Participants receive 200 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 300 mg QW Participants receive 300 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 250 mg QW Participants receive 250 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 150 mg QW Participants receive 150 mg oral MK-2206 QW in repeating 4-week treatment cycles.
Concentration of MK-2206 After 48 Hours (C48hr) in Participants Receiving Multiple QOD Dosing Day 1	14.1 nM Standard Deviation 5.38	30.9 nM Standard Deviation 14.4	30.6 nM Standard Deviation 12.0	64.1 nM Standard Deviation 28.0	—	—	—	—	—	—
Concentration of MK-2206 After 48 Hours (C48hr) in Participants Receiving Multiple QOD Dosing Last Day (Day 27)	67.9 nM Standard Deviation NA Standard Deviation could not be calculated since the N=1.	100 nM Standard Deviation 45.6	110 nM Standard Deviation NA Standard Deviation could not be calculated since the N=1.	134 nM Standard Deviation 112	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Days 1 and 27: predose and 0.5, 1, 2, 3, 4, 6, 10, 24, and 48 hours after MK-2206 dosing

Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. Tmax was calculated for Day 1 and the last day of treatment in Cycle 1 and reported for all dose levels receiving MK-2206 orally QOD (30, 60, 75, and 90 mg QOD).

Outcome measures

Outcome measures
Measure	MK-2206 30 mg QOD n=3 Participants Participants receive 30 mg oral MK-2206 every other day (QOD) in repeating 4-week treatment cycles.	MK-2206 60 mg QOD n=58 Participants Participants receive 60 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 75 mg QOD n=3 Participants Participants receive 75 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QOD n=7 Participants Participants receive 90 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QW Participants receive 90 mg oral MK-2206 every week (QW) in repeating 4-week treatment cycles.	MK-2206 135 mg QW Participants receive 135 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 200 mg QW Participants receive 200 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 300 mg QW Participants receive 300 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 250 mg QW Participants receive 250 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 150 mg QW Participants receive 150 mg oral MK-2206 QW in repeating 4-week treatment cycles.
Time to Maximum Concentration (Tmax) of MK-2206 in Participants Receiving Multiple QOD Dosing Day 1	6.0 hour Interval 4.0 to 6.0	4.0 hour Interval 2.0 to 24.0	6.0 hour Interval 4.0 to 6.0	6.0 hour Interval 4.0 to 10.0	—	—	—	—	—	—
Time to Maximum Concentration (Tmax) of MK-2206 in Participants Receiving Multiple QOD Dosing Last Day (Day 27)	4.0 hour Interval 4.0 to 4.0	6.0 hour Interval 3.0 to 24.0	10.0 hour Interval 10.0 to 10.0	5.0 hour Interval 4.0 to 6.0	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Day 27: predose and 0.5, 1, 2, 3, 4, 6, 10, 24, and 48 hours after MK-2206 dosing.

Population: All participants who received MK-2206 orally QOD on Day 27 of Cycle 1 (30, 60, 75, and 90 mg QOD) and had available PK data. Data for the MK-2206 QW dose groups (90, 135, 200, 300, 250, and 150 mg QW) are reported separately.

Blood samples were collected for PK analyses on Day 27 of the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. t½ (Harmonic mean ± pseudo SD) was calculated and reported for all dose levels receiving MK-2206 orally QOD (30, 60, 75, and 90 mg QOD).

Outcome measures

Outcome measures
Measure	MK-2206 30 mg QOD n=1 Participants Participants receive 30 mg oral MK-2206 every other day (QOD) in repeating 4-week treatment cycles.	MK-2206 60 mg QOD n=44 Participants Participants receive 60 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 75 mg QOD n=1 Participants Participants receive 75 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QOD n=2 Participants Participants receive 90 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QW Participants receive 90 mg oral MK-2206 every week (QW) in repeating 4-week treatment cycles.	MK-2206 135 mg QW Participants receive 135 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 200 mg QW Participants receive 200 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 300 mg QW Participants receive 300 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 250 mg QW Participants receive 250 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 150 mg QW Participants receive 150 mg oral MK-2206 QW in repeating 4-week treatment cycles.
Apparent Terminal Half-life (t½) of MK-2206 in Participants Receiving Multiple QOD Dosing	62.7 hour Standard Deviation 15.1	66.3 hour Standard Deviation 17.0	66.2 hour Standard Deviation 4.9	65.6 hour Standard Deviation 0	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Days 1 and 22: predose and 2, 4, 6, 10, 24, 48, 96 hours, and 168 hours after MK-2206 dosing

Population: All participants who received MK-2206 orally QW during Cycle 1 (90, 135, 200, 300, 250, and 150 mg QW) and had available PK data. Data for the MK-2206 QOD dose groups (30, 60, 75, and 90 mg QOD) are reported separately.

Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. AUC 0-168 was calculated for Day 1 and the last day of treatment in Cycle 1 and reported for all dose levels receiving MK-2206 orally QW (90, 135, 200, 300, 250, and 150 mg QW).

Outcome measures

Outcome measures
Measure	MK-2206 30 mg QOD Participants receive 30 mg oral MK-2206 every other day (QOD) in repeating 4-week treatment cycles.	MK-2206 60 mg QOD Participants receive 60 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 75 mg QOD Participants receive 75 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QOD Participants receive 90 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QW n=3 Participants Participants receive 90 mg oral MK-2206 every week (QW) in repeating 4-week treatment cycles.	MK-2206 135 mg QW n=5 Participants Participants receive 135 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 200 mg QW n=17 Participants Participants receive 200 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 300 mg QW n=3 Participants Participants receive 300 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 250 mg QW n=3 Participants Participants receive 250 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 150 mg QW n=2 Participants Participants receive 150 mg oral MK-2206 QW in repeating 4-week treatment cycles.
AUC0-168hr in Participants Receiving Multiple QW Dosing Last Day (Day 22)	—	—	—	—	10600 nM•hr Standard Deviation 7520	20700 nM•hr Standard Deviation 8780	23500 nM•hr Standard Deviation 14700	—	10700 nM•hr Standard Deviation NA Standard Deviation could not be calculated since the N=1.	22600 nM•hr Standard Deviation 0
AUC0-168hr in Participants Receiving Multiple QW Dosing Day 1	—	—	—	—	6510 nM•hr Standard Deviation 3810	12000 nM•hr Standard Deviation 4610	16400 nM•hr Standard Deviation 5470	27700 nM•hr Standard Deviation 3320	14000 nM•hr Standard Deviation 2950	20700 nM•hr Standard Deviation 0

PRIMARY outcome

Timeframe: Days 1 and 22: predose and 2, 4, 6, 10, 24, 48, 96 hours, and 168 hours after MK-2206 dosing

Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. Cmax was calculated for Day 1 and the last day of treatment in Cycle 1 and reported for all dose levels receiving MK-2206 orally QW (90, 135, 200, 300, 250, and 150 mg QW).

Outcome measures

Outcome measures
Measure	MK-2206 30 mg QOD Participants receive 30 mg oral MK-2206 every other day (QOD) in repeating 4-week treatment cycles.	MK-2206 60 mg QOD Participants receive 60 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 75 mg QOD Participants receive 75 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QOD Participants receive 90 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QW n=3 Participants Participants receive 90 mg oral MK-2206 every week (QW) in repeating 4-week treatment cycles.	MK-2206 135 mg QW n=5 Participants Participants receive 135 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 200 mg QW n=17 Participants Participants receive 200 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 300 mg QW n=3 Participants Participants receive 300 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 250 mg QW n=3 Participants Participants receive 250 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 150 mg QW n=2 Participants Participants receive 150 mg oral MK-2206 QW in repeating 4-week treatment cycles.
Cmax of MK-2206 in Participants Receiving Multiple QW Dosing Day 1	—	—	—	—	81.7 nM Standard Deviation 42.4	199 nM Standard Deviation 98.9	264 nM Standard Deviation 75.8	466 nM Standard Deviation 123	231 nM Standard Deviation 39.1	337 nM Standard Deviation 0
Cmax of MK-2206 in Participants Receiving Multiple QW Dosing Last Day (Day 22)	—	—	—	—	153 nM Standard Deviation 98.0	352 nM Standard Deviation 210	345 nM Standard Deviation 199	—	169 nM Standard Deviation NA Standard Deviation could not be calculated since the N=1.	346 nM Standard Deviation NA Standard Deviation could not be calculated since the N=1.

PRIMARY outcome

Timeframe: Days 1 and 22: predose and 48 hours after MK-2206 dosing

Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. C48hr was calculated for Day 1 and the last day of treatment in Cycle 1 and reported for all dose levels receiving MK-2206 orally QW (90, 135, 200, 300, 250, and 150 mg QW).

Outcome measures

Outcome measures
Measure	MK-2206 30 mg QOD Participants receive 30 mg oral MK-2206 every other day (QOD) in repeating 4-week treatment cycles.	MK-2206 60 mg QOD Participants receive 60 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 75 mg QOD Participants receive 75 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QOD Participants receive 90 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QW n=3 Participants Participants receive 90 mg oral MK-2206 every week (QW) in repeating 4-week treatment cycles.	MK-2206 135 mg QW n=5 Participants Participants receive 135 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 200 mg QW n=17 Participants Participants receive 200 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 300 mg QW n=3 Participants Participants receive 300 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 250 mg QW n=3 Participants Participants receive 250 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 150 mg QW n=2 Participants Participants receive 150 mg oral MK-2206 QW in repeating 4-week treatment cycles.
C48hr of MK-2206 in Participants Receiving Multiple QW Dosing Day 1	—	—	—	—	50.9 nM Standard Deviation 38.2	90.3 nM Standard Deviation 25.1	121 nM Standard Deviation 47.4	253 nM Standard Deviation 0	103 nM Standard Deviation 19.6	155 nM Standard Deviation 0
C48hr of MK-2206 in Participants Receiving Multiple QW Dosing Last Day (Day 22)	—	—	—	—	79.3 nM Standard Deviation 33.7	158 nM Standard Deviation 59.2	187 nM Standard Deviation 113	—	74.8 nM Standard Deviation 0	185 nM Standard Deviation 0

PRIMARY outcome

Timeframe: Days 1 and 22: predose and 2, 4, 6, 10, 24, 48, 96 hours, and 168 hours after MK-2206 dosing

Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. Tmax was calculated for Day 1 and the last day of treatment in Cycle 1 and reported for all dose levels receiving MK-2206 orally QW (90, 135, 200, 300, 250, and 150 mg QW).

Outcome measures

Outcome measures
Measure	MK-2206 30 mg QOD Participants receive 30 mg oral MK-2206 every other day (QOD) in repeating 4-week treatment cycles.	MK-2206 60 mg QOD Participants receive 60 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 75 mg QOD Participants receive 75 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QOD Participants receive 90 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QW n=3 Participants Participants receive 90 mg oral MK-2206 every week (QW) in repeating 4-week treatment cycles.	MK-2206 135 mg QW n=5 Participants Participants receive 135 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 200 mg QW n=17 Participants Participants receive 200 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 300 mg QW n=3 Participants Participants receive 300 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 250 mg QW n=3 Participants Participants receive 250 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 150 mg QW n=2 Participants Participants receive 150 mg oral MK-2206 QW in repeating 4-week treatment cycles.
Tmax of MK-2206 in Participants Receiving Multiple QW Dosing Day 1	—	—	—	—	6.0 hour Interval 4.0 to 10.0	4.0 hour Interval 4.0 to 10.0	6.0 hour Interval 4.0 to 10.0	4.0 hour Interval 4.0 to 6.0	6.0 hour Interval 4.0 to 6.0	7.0 hour Interval 4.0 to 10.0
Tmax of MK-2206 in Participants Receiving Multiple QW Dosing Last Day (Day 22)	—	—	—	—	4.0 hour Interval 4.0 to 4.0	5.0 hour Interval 4.0 to 24.0	6.0 hour Interval 4.0 to 24.0	—	4.0 hour Interval 4.0 to 4.0	4.0 hour Interval 4.0 to 4.0

PRIMARY outcome

Timeframe: Day 22: predose and 2, 4, 6, 10, 24, 48, 96 hours, and 168 hours after MK-2206 dosing

Population: All participants who received MK-2206 orally QW on Day 22 of Cycle 1 (90, 135, 200, 300, 250, and 150 mg QW) and had available PK data. Data for the MK-2206 QOD dose groups (30, 60, 75, and 90 mg QOD) are reported separately.

Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. t½ (Harmonic mean ± pseudo SD) was calculated for the last day of treatment in Cycle 1 and reported for all dose levels receiving MK-2206 orally QW (90, 135, 200, 300, 250, and 150 mg QW).

Outcome measures

Outcome measures
Measure	MK-2206 30 mg QOD Participants receive 30 mg oral MK-2206 every other day (QOD) in repeating 4-week treatment cycles.	MK-2206 60 mg QOD Participants receive 60 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 75 mg QOD Participants receive 75 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QOD Participants receive 90 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QW n=3 Participants Participants receive 90 mg oral MK-2206 every week (QW) in repeating 4-week treatment cycles.	MK-2206 135 mg QW n=4 Participants Participants receive 135 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 200 mg QW n=13 Participants Participants receive 200 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 300 mg QW Participants receive 300 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 250 mg QW n=1 Participants Participants receive 250 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 150 mg QW n=1 Participants Participants receive 150 mg oral MK-2206 QW in repeating 4-week treatment cycles.
t½ of MK-2206 in Participants Receiving Multiple QW Dosing	—	—	—	—	71.6 hour Standard Deviation 12.2	88.9 hour Standard Deviation 26.9	75.1 hour Standard Deviation 14.7	—	53.7 hour Standard Deviation 0	64.4 hour Standard Deviation 0

SECONDARY outcome

Timeframe: Baseline, Cycle 1 Day 15

Population: Participants treated at the MTD (60 mg QOD) dose level with measurable disease at baseline per RECIST and paired tumor samples at baseline and C1D15. Per protocol, no other dose level groups were analyzed.

To determine the inhibition of pAkt by MK-2206 in participants treated at the MTD, levels of Akt phosphorylated at the serine 473 residue (pAkt Ser473 Akt) were measured in snap-frozen tumors collected at baseline and Day 15 of Cycle 1 using a MesoScale enzyme-linked immunosorbent assay (ELISA). Per protocol, pAkt levels were determined only for the MK-2206 MTD (60 mg QOD) group.

Outcome measures

Outcome measures
Measure	MK-2206 30 mg QOD Participants receive 30 mg oral MK-2206 every other day (QOD) in repeating 4-week treatment cycles.	MK-2206 60 mg QOD n=7 Participants Participants receive 60 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 75 mg QOD Participants receive 75 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QOD Participants receive 90 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QW Participants receive 90 mg oral MK-2206 every week (QW) in repeating 4-week treatment cycles.	MK-2206 135 mg QW Participants receive 135 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 200 mg QW Participants receive 200 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 300 mg QW Participants receive 300 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 250 mg QW Participants receive 250 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 150 mg QW Participants receive 150 mg oral MK-2206 QW in repeating 4-week treatment cycles.
Phosphorylated Protein Kinase B (pAkt) Level on Cycle 1 Day 15 (C1D15) After Treatment With MK-2206 at the Maximum Tolerated Dose (MTD) Baseline	—	2.15 pAkt lysate units/mg protein Interval 0.43 to 10.49	—	—	—	—	—	—	—	—
Phosphorylated Protein Kinase B (pAkt) Level on Cycle 1 Day 15 (C1D15) After Treatment With MK-2206 at the Maximum Tolerated Dose (MTD) Cycle 1 Day 15	—	0.29 pAkt lysate units/mg protein Interval 0.13 to 0.64	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From Cycle 1 Day 1 through the End of Study Visit (up to 6 months)

Population: All participants with measurable disease at baseline per RECIST.

Overall tumor response was assessed during the study by diagnostic anatomic imaging using RECIST. The number of participants with a confirmed Complete Response (CR: Disappearance of all target lesions) as per RECIST was reported for each dose level group.

Outcome measures

Outcome measures
Measure	MK-2206 30 mg QOD n=3 Participants Participants receive 30 mg oral MK-2206 every other day (QOD) in repeating 4-week treatment cycles.	MK-2206 60 mg QOD n=58 Participants Participants receive 60 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 75 mg QOD n=3 Participants Participants receive 75 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QOD n=7 Participants Participants receive 90 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QW n=3 Participants Participants receive 90 mg oral MK-2206 every week (QW) in repeating 4-week treatment cycles.	MK-2206 135 mg QW n=5 Participants Participants receive 135 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 200 mg QW n=17 Participants Participants receive 200 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 300 mg QW n=3 Participants Participants receive 300 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 250 mg QW n=3 Participants Participants receive 250 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 150 mg QW n=2 Participants Participants receive 150 mg oral MK-2206 QW in repeating 4-week treatment cycles.
Number of Participants With Confirmed Response as Per Response Evaluation Criteria in Solid Tumors (RECIST)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	MK-2206 30 mg QOD n=3 participants at risk Participants receive 30 mg oral MK-2206 every other day (QOD) in repeating 4-week treatment cycles.	MK-2206 60 mg QOD n=58 participants at risk Participants receive 60 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 75 mg QOD n=3 participants at risk Participants receive 75 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QOD n=7 participants at risk Participants receive 90 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QW n=3 participants at risk Participants receive 90 mg oral MK-2206 every week (QW) in repeating 4-week treatment cycles.	MK-2206 135 mg QW n=5 participants at risk Participants receive 135 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 200 mg QW n=17 participants at risk Participants receive 200 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 300 mg QW n=3 participants at risk Participants receive 300 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 250 mg QW n=3 participants at risk Participants receive 250 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 150 mg QW n=2 participants at risk Participants receive 150 mg oral MK-2206 QW in repeating 4-week treatment cycles.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Anaemia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Cardiac disorders Atrial fibrillation	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Cardiac disorders Atrioventricular block complete	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Eye disorders Conjunctivitis	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Ascites	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Nausea	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Stomatitis	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Vomiting	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
General disorders Pyrexia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.2% 3/58 • Number of events 3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Infections and infestations Abdominal abscess	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	20.0% 1/5 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Infections and infestations Abscess	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Infections and infestations Cellulitis	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Infections and infestations Sepsis	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	3.4% 2/58 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Infections and infestations Urinary tract infection	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Investigations QRS axis abnormal	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic carcinoid tumour	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	12.1% 7/58 • Number of events 7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	40.0% 2/5 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	11.8% 2/17 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Nervous system disorders Convulsion	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	20.0% 1/5 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Nervous system disorders Neuropathy peripheral	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Renal and urinary disorders Renal failure acute	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Rash	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	8.6% 5/58 • Number of events 5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	42.9% 3/7 • Number of events 4 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	17.6% 3/17 • Number of events 3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Rash generalised	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Vascular disorders Deep vein thrombosis	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	20.0% 1/5 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Vascular disorders Vascular compression	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.

Other adverse events

Other adverse events
Measure	MK-2206 30 mg QOD n=3 participants at risk Participants receive 30 mg oral MK-2206 every other day (QOD) in repeating 4-week treatment cycles.	MK-2206 60 mg QOD n=58 participants at risk Participants receive 60 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 75 mg QOD n=3 participants at risk Participants receive 75 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QOD n=7 participants at risk Participants receive 90 mg oral MK-2206 QOD in repeating 4-week treatment cycles.	MK-2206 90 mg QW n=3 participants at risk Participants receive 90 mg oral MK-2206 every week (QW) in repeating 4-week treatment cycles.	MK-2206 135 mg QW n=5 participants at risk Participants receive 135 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 200 mg QW n=17 participants at risk Participants receive 200 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 300 mg QW n=3 participants at risk Participants receive 300 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 250 mg QW n=3 participants at risk Participants receive 250 mg oral MK-2206 QW in repeating 4-week treatment cycles.	MK-2206 150 mg QW n=2 participants at risk Participants receive 150 mg oral MK-2206 QW in repeating 4-week treatment cycles.
Investigations Weight decreased	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	66.7% 2/3 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	20.0% 1/5 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Decreased appetite	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	27.6% 16/58 • Number of events 22 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	66.7% 2/3 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	28.6% 2/7 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	20.0% 1/5 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	23.5% 4/17 • Number of events 4 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	100.0% 2/2 • Number of events 4 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	20.0% 1/5 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	13.8% 8/58 • Number of events 17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	66.7% 2/3 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	28.6% 2/7 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	20.0% 1/5 • Number of events 4 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	20.0% 1/5 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Psychiatric disorders Insomnia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Renal and urinary disorders Renal tubular necrosis	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Nervous system disorders Somnolence	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	20.0% 1/5 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Nervous system disorders VIIth nerve paralysis	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Psychiatric disorders Anxiety	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.2% 3/58 • Number of events 3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Psychiatric disorders Depressed mood	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.2% 3/58 • Number of events 3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	20.0% 1/5 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Reproductive system and breast disorders Gynaecomastia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	6.9% 4/58 • Number of events 6 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	20.0% 1/5 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	11.8% 2/17 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	13.8% 8/58 • Number of events 9 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	23.5% 4/17 • Number of events 5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Renal and urinary disorders Urinary incontinence	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Hydropneumothorax	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.2% 3/58 • Number of events 3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Anaemia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.2% 3/58 • Number of events 3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	20.0% 1/5 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Leukopenia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	3.4% 2/58 • Number of events 3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	28.6% 2/7 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.2% 3/58 • Number of events 5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Monocytopenia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Neutropenia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.2% 3/58 • Number of events 4 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Cardiac disorders Atrioventricular block first degree	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Cardiac disorders Myocardial ischaemia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Cardiac disorders Tachycardia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Ear and labyrinth disorders Ear congestion	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Ear and labyrinth disorders Tinnitus	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Endocrine disorders Hypothyroidism	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Eye disorders Cataract	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	11.8% 2/17 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Eye disorders Conjunctivitis	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Eye disorders Corneal disorder	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Eye disorders Dry eye	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Eye disorders Eye disorder	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	8.6% 5/58 • Number of events 5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Eye disorders Eye swelling	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Eye disorders Lens disorder	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Eye disorders Maculopathy	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Eye disorders Myopia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Eye disorders Optic disc disorder	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Eye disorders Vision blurred	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal distension	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	3.4% 2/58 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	8.6% 5/58 • Number of events 7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	11.8% 2/17 • Number of events 4 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	100.0% 2/2 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	3.4% 2/58 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Ascites	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Constipation	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	17.2% 10/58 • Number of events 15 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	20.0% 1/5 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	23.5% 4/17 • Number of events 4 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Diarrhoea	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	13.8% 8/58 • Number of events 11 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	57.1% 4/7 • Number of events 6 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	29.4% 5/17 • Number of events 5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	66.7% 2/3 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Dry mouth	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Dyspepsia	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	8.6% 5/58 • Number of events 5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Enterocutaneous fistula	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Haematochezia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Lip pain	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Nausea	66.7% 2/3 • Number of events 3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	37.9% 22/58 • Number of events 31 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	42.9% 3/7 • Number of events 3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	41.2% 7/17 • Number of events 9 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 4 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Odynophagia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Oral mucosal exfoliation	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Stomatitis	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.2% 3/58 • Number of events 4 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	71.4% 5/7 • Number of events 8 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	17.6% 3/17 • Number of events 3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Gastrointestinal disorders Vomiting	33.3% 1/3 • Number of events 3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	27.6% 16/58 • Number of events 28 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	23.5% 4/17 • Number of events 4 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	100.0% 2/2 • Number of events 4 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
General disorders Chest discomfort	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
General disorders Chest pain	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
General disorders Fatigue	33.3% 1/3 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	44.8% 26/58 • Number of events 34 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	28.6% 2/7 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	66.7% 2/3 • Number of events 3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	47.1% 8/17 • Number of events 10 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	66.7% 2/3 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	100.0% 2/2 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
General disorders Influenza like illness	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
General disorders Mucosal inflammation	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
General disorders Oedema peripheral	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	3.4% 2/58 • Number of events 3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	66.7% 2/3 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	20.0% 1/5 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
General disorders Pain	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	3.4% 2/58 • Number of events 3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	11.8% 2/17 • Number of events 4 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
General disorders Performance status decreased	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
General disorders Pyrexia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	6.9% 4/58 • Number of events 6 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	42.9% 3/7 • Number of events 4 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	20.0% 1/5 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	11.8% 2/17 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
General disorders Thirst	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Infections and infestations Infection	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Infections and infestations Paronychia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Infections and infestations Respiratory tract infection viral	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Infections and infestations Skin infection	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Infections and infestations Vulvovaginal candidiasis	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Accidental overdose	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	8.6% 5/58 • Number of events 5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Skin injury	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Investigations Alanine aminotransferase increased	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	6.9% 4/58 • Number of events 7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	20.0% 1/5 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	100.0% 2/2 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Investigations Aspartate aminotransferase increased	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	6.9% 4/58 • Number of events 5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Investigations Blood alkaline phosphatase increased	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	8.6% 5/58 • Number of events 10 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	20.0% 1/5 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	100.0% 2/2 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Investigations Blood creatinine increased	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Investigations Blood lactate dehydrogenase increased	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.2% 3/58 • Number of events 3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Investigations Gamma-glutamyltransferase increased	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Investigations Transaminases increased	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.2% 3/58 • Number of events 4 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	20.0% 1/5 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	10.3% 6/58 • Number of events 6 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	15.5% 9/58 • Number of events 10 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	3.4% 2/58 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	66.7% 2/3 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	3.4% 2/58 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	11.8% 2/17 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	12.1% 7/58 • Number of events 7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	1.7% 1/58 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	12.1% 7/58 • Number of events 8 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	20.0% 1/5 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	8.6% 5/58 • Number of events 5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Nervous system disorders Dizziness	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	3.4% 2/58 • Number of events 3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Nervous system disorders Dysgeusia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	3.4% 2/58 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Nervous system disorders Headache	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	15.5% 9/58 • Number of events 10 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	20.0% 1/5 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	11.8% 2/17 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Nervous system disorders Hypoaesthesia	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Nervous system disorders Neuropathy peripheral	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Nervous system disorders Sensory loss	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pharyngeal inflammation	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Throat tightness	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	14.3% 1/7 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Dermatitis acneiform	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	20.0% 1/5 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	12.1% 7/58 • Number of events 7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	28.6% 2/7 • Number of events 3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	11.8% 2/17 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	13.8% 8/58 • Number of events 11 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	66.7% 2/3 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	28.6% 2/7 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	20.0% 1/5 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	11.8% 2/17 • Number of events 3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Rash	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	44.8% 26/58 • Number of events 41 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	100.0% 3/3 • Number of events 5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	57.1% 4/7 • Number of events 4 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	40.0% 2/5 • Number of events 2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	29.4% 5/17 • Number of events 13 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	100.0% 3/3 • Number of events 8 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	66.7% 2/3 • Number of events 5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	100.0% 2/2 • Number of events 3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Rash macular	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.2% 3/58 • Number of events 4 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	50.0% 1/2 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Skin haemorrhage	33.3% 1/3 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/17 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.
Vascular disorders Aneurysm	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/58 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/7 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/5 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	5.9% 1/17 • Number of events 1 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/3 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.	0.00% 0/2 • Up to 269 days APaT population: All participants who received at least one dose of study treatment.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission. SPONSOR review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER