Trial Outcomes & Findings for A Study Evaluating Dalotuzumab (MK-0646) in Combination With Erlotinib for Participants With Non-Small Cell Lung Cancer (MK-0646-007) (NCT NCT00654420)

NCT ID: NCT00654420

Last Updated: 2018-08-08

Results Overview

A DLT was an AE related (definitely, probably, or possibly) to study therapy and occurring within first 4 weeks of therapy. Hematologic DLTs included Grade (Gr)4 neutropenia lasting for ≥7 days, Gr 3/Gr 4 neutropenia with fever \>38.5 °C and/or infection requiring antibiotic or anti-fungal treatment, and Gr 4 thrombocytopenia (25.0 x 10\^9/L). Non-hematologic DLT defined as any ≥Gr 3 nonhematologic toxicity, except Gr 3 reversible rash; Gr 3 nausea, vomiting, diarrhea, dehydration, or hyperglycemia occurring in setting of inadequate compliance with supportive care; alopecia; anorexia; asthenia; inadequately-treated hypersensitivity reactions; Gr 3 elevated transaminases (≤1 week duration); or infusion reactions to dalotuzumab. Any drug-related AEs that led to dose modification of dalotuzumab/erlotinib or any unresolved drug-related toxicity that caused a ≥3 week delay of next scheduled dose of study drug, regardless of Common Terminology Criteria grade, were DLTs.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 95 participants
• Primary outcome timeframe: Up to 4 weeks after initiation of treatment
• Results posted on: 2018-08-08

Participant Flow

20 participants were enrolled in Phase I part (dose escalation) and 75 participants were enrolled in Phase II part of study (95 total enrolled).

Participant milestones

Measure	Ph I: Dalotuzumab 5 mg/kg + Erlotinib During the Phase I part of the study, participants received dalotuzumab intravenously (IV) at 5 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who did not have disease progression and were satisfactorily tolerating study drug could continue to receive study drug.	Ph I: Dalotuzumab 10 mg/kg + Erlotinib During the Phase I part of the study, participants received dalotuzumab IV at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who did not have disease progression and were satisfactorily tolerating study drug could continue to receive study drug.	Ph II: Dalotuzumab 10 mg/kg + Erlotinib During the Phase II part of the study, participants were randomized to receive dalotuzumab IV at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.	Ph II: Erlotinib During the Phase II part of the study, participants were randomized to receive open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.
Phase I (Dose Escalation) STARTED	4	16	0	0
Phase I (Dose Escalation) COMPLETED	0	0	0	0
Phase I (Dose Escalation) NOT COMPLETED	4	16	0	0
Phase II STARTED	0	0	37	38
Phase II COMPLETED	0	0	0	0
Phase II NOT COMPLETED	0	0	37	38

Reasons for withdrawal

Measure	Ph I: Dalotuzumab 5 mg/kg + Erlotinib During the Phase I part of the study, participants received dalotuzumab intravenously (IV) at 5 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who did not have disease progression and were satisfactorily tolerating study drug could continue to receive study drug.	Ph I: Dalotuzumab 10 mg/kg + Erlotinib During the Phase I part of the study, participants received dalotuzumab IV at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who did not have disease progression and were satisfactorily tolerating study drug could continue to receive study drug.	Ph II: Dalotuzumab 10 mg/kg + Erlotinib During the Phase II part of the study, participants were randomized to receive dalotuzumab IV at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.	Ph II: Erlotinib During the Phase II part of the study, participants were randomized to receive open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.
Phase I (Dose Escalation) Adverse Event	0	1	0	0
Phase I (Dose Escalation) Progressive Disease	4	15	0	0
Phase II Adverse Event	0	0	3	3
Phase II Lost to Follow-up	0	0	0	1
Phase II Physician Decision	0	0	0	4
Phase II Progressive Disease	0	0	29	29
Phase II Withdrawal by Subject	0	0	4	1
Phase II Missing Disposition Record	0	0	1	0

Baseline Characteristics

A Study Evaluating Dalotuzumab (MK-0646) in Combination With Erlotinib for Participants With Non-Small Cell Lung Cancer (MK-0646-007)

Baseline characteristics by cohort

Measure	Ph I: Dalotuzumab 5 mg/kg + Erlotinib n=4 Participants During the Phase I part of the study, participants received dalotuzumab IV at 5 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who did not have disease progression and were satisfactorily tolerating study drug could continue to receive study drug.	Ph I: Dalotuzumab 10 mg/kg + Erlotinib n=16 Participants During the Phase I part of the study, participants received dalotuzumab IV at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who did not have disease progression and were satisfactorily tolerating study drug could continue to receive study drug.	Ph II: Dalotuzumab 10 mg/kg + Erlotinib n=37 Participants During the Phase II part of the study, participants were randomized to receive dalotuzumab IV at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.	Ph II: Erlotinib n=38 Participants During the Phase II part of the study, participants were randomized to receive open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.	Total n=95 Participants Total of all reporting groups
Age, Continuous	53.8 years STANDARD_DEVIATION 3.86 • n=5 Participants	61.9 years STANDARD_DEVIATION 7.68 • n=7 Participants	61.9 years STANDARD_DEVIATION 7.83 • n=5 Participants	58.5 years STANDARD_DEVIATION 10.35 • n=4 Participants	60.2 years STANDARD_DEVIATION 8.95 • n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	2 Participants n=7 Participants	10 Participants n=5 Participants	10 Participants n=4 Participants	22 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	14 Participants n=7 Participants	27 Participants n=5 Participants	28 Participants n=4 Participants	73 Participants n=21 Participants

PRIMARY outcome

Timeframe: Up to 4 weeks after initiation of treatment

Population: Participants in the Phase I part of the study who received at least one dose of dalotuzumab in combination with erlotinib during the first 4 weeks of treatment and were evaluable for DLT assessment. Participants in the Phase II part of the study were not evaluated for DLTs.

A DLT was an AE related (definitely, probably, or possibly) to study therapy and occurring within first 4 weeks of therapy.

Hematologic DLTs included Grade (Gr)4 neutropenia lasting for ≥7 days, Gr 3/Gr 4 neutropenia with fever >38.5 °C and/or infection requiring antibiotic or anti-fungal treatment, and Gr 4 thrombocytopenia (25.0 x 10^9/L).

Non-hematologic DLT defined as any ≥Gr 3 nonhematologic toxicity, except Gr 3 reversible rash; Gr 3 nausea, vomiting, diarrhea, dehydration, or hyperglycemia occurring in setting of inadequate compliance with supportive care; alopecia; anorexia; asthenia; inadequately-treated hypersensitivity reactions; Gr 3 elevated transaminases (≤1 week duration); or infusion reactions to dalotuzumab.

Any drug-related AEs that led to dose modification of dalotuzumab/erlotinib or any unresolved drug-related toxicity that caused a ≥3 week delay of next scheduled dose of study drug, regardless of Common Terminology Criteria grade, were DLTs.

Outcome measures

Measure	Ph I: Dalotuzumab 5 mg/kg + Erlotinib n=4 Participants During the Phase I part of the study, participants received dalotuzumab IV at 5 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who did not have disease progression and were satisfactorily tolerating study drug could continue to receive study drug.	Ph I: Dalotuzumab 10 mg/kg + Erlotinib n=13 Participants During the Phase I part of the study, participants received dalotuzumab IV at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who did not have disease progression and were satisfactorily tolerating study drug could continue to receive study drug.	Ph II: Dalotuzumab 10 mg/kg + Erlotinib During the Phase II part of the study, participants were randomized to receive dalotuzumab IV at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.	Ph II: Erlotinib During the Phase II part of the study, participants were randomized to receive open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.
Phase I: Number of Participants Experiencing at Least One Dose-Limiting Toxicity (DLT) Adverse Event (AE) During the First Four Weeks of Dalotuzumab Plus Erlotinib Treatment	0 participants	1 participants	—	—

PRIMARY outcome

Timeframe: Duration of time required to collect approximately 49 deaths or PFS events (assessed up to ~20 months total on this study from randomization to cut-off date)

Population: All randomized participants in Phase II who received ≥1 dose of study treatment, had a baseline radiological (CT or MRI) disease assessment, and had ≥1 post-baseline radiological (CT or MRI) disease assessment subsequent to ≥1 dose of study treatment for reason other than discontinuation for AE. Phase I participants were not assessed for PFS.

PFS was defined as the time from randomization until either the emergence of radiographic evidence of disease progression or death due to any cause, whichever occurs first. Disease progression was classified as a radiographic assessment of progressive disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) using computed tomography (CT) or magnetic resonance imaging (MRI). As pre-specified by the protocol, final analysis of PFS was to take place after approximately 49 PFS events or deaths had occurred in the Phase II part of the trial. A non-parametric Kaplan-Meier method was used to estimate the median PFS time for each treatment group. Participants who discontinued from the study for reasons other than progression of disease were treated as right-censored observations at the time of the last response evaluation. Participants who withdrew from the study due to PD were considered to have a disease progression between the last visit and the time of withdrawal.

Outcome measures

Measure	Ph I: Dalotuzumab 5 mg/kg + Erlotinib During the Phase I part of the study, participants received dalotuzumab IV at 5 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who did not have disease progression and were satisfactorily tolerating study drug could continue to receive study drug.	Ph I: Dalotuzumab 10 mg/kg + Erlotinib During the Phase I part of the study, participants received dalotuzumab IV at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who did not have disease progression and were satisfactorily tolerating study drug could continue to receive study drug.	Ph II: Dalotuzumab 10 mg/kg + Erlotinib n=36 Participants During the Phase II part of the study, participants were randomized to receive dalotuzumab IV at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.	Ph II: Erlotinib n=36 Participants During the Phase II part of the study, participants were randomized to receive open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.
Phase II: Median Progression Free Survival (PFS) in Participants Receiving Dalotuzumab Plus Erlotinib Treatment	—	—	2.5 months Interval 1.4 to 5.3	1.6 months Interval 1.3 to 2.7

SECONDARY outcome

Timeframe: Duration of time required to collect approximately 49 deaths or PFS events (assessed up to ~20 months total on this study from randomization to cut-off date)

Population: Intent to Treat (IIT) Population; all randomized participants in Phase II included regardless of compliance to planned treatment. Phase I participants were not assessed for OS.

OS was defined as the time from randomization to death in months due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. The nonparametric Kaplan-Meier method was used to estimate the survival time distribution and the median survival of each treatment group.

Outcome measures

Measure	Ph I: Dalotuzumab 5 mg/kg + Erlotinib During the Phase I part of the study, participants received dalotuzumab IV at 5 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who did not have disease progression and were satisfactorily tolerating study drug could continue to receive study drug.	Ph I: Dalotuzumab 10 mg/kg + Erlotinib During the Phase I part of the study, participants received dalotuzumab IV at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who did not have disease progression and were satisfactorily tolerating study drug could continue to receive study drug.	Ph II: Dalotuzumab 10 mg/kg + Erlotinib n=37 Participants During the Phase II part of the study, participants were randomized to receive dalotuzumab IV at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.	Ph II: Erlotinib n=38 Participants During the Phase II part of the study, participants were randomized to receive open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.
Phase II: Median Overall Survival (OS) in Participants Receiving Dalotuzumab Plus Erlotinib Treatment	—	—	6.9 months Interval 5.2 to 14.7	14.5 months Interval 8.2 to A statistical estimate of the upper bound is not available based on the model used for the data analysis.

SECONDARY outcome

Timeframe: Duration of time required to collect approximately 49 deaths or PFS events (assessed up to ~20 months total on this study from randomization to cut-off date)

Population: All randomized participants in Phase II who received ≥1 dose of study treatment, had a baseline radiological (CT or MRI) disease assessment, and had ≥1 post-baseline radiological (CT or MRI) disease assessment subsequent to ≥1 dose of study treatment for reason other than discontinuation for AE. Phase I participants were not assessed for ORR.

ORR was defined as the percentage of participants in the Phase II analysis population having complete response (CR) or partial response (PR) during the course of the study.

RECIST criteria were used to quantify response rate. For evaluation of target lesions, CR was defined as disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of the LD. For evaluation of non-target lesions, CR was defined as disappearance of all non-target lesions and normalization of tumor marker level.

Confirmation of response required a second assessment performed 4 weeks or more after the initial assessment. If the confirmation assessment contradicted the initial assessment, it was considered that a response had not been observed. If the confirmation assessment of a participant was not available, that participant was not considered as a responder in the response rate analyses.

Outcome measures

Measure	Ph I: Dalotuzumab 5 mg/kg + Erlotinib During the Phase I part of the study, participants received dalotuzumab IV at 5 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who did not have disease progression and were satisfactorily tolerating study drug could continue to receive study drug.	Ph I: Dalotuzumab 10 mg/kg + Erlotinib During the Phase I part of the study, participants received dalotuzumab IV at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who did not have disease progression and were satisfactorily tolerating study drug could continue to receive study drug.	Ph II: Dalotuzumab 10 mg/kg + Erlotinib n=36 Participants During the Phase II part of the study, participants were randomized to receive dalotuzumab IV at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.	Ph II: Erlotinib n=36 Participants During the Phase II part of the study, participants were randomized to receive open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.
Phase II: Percentage of Participants With Complete Response (CR) or Partial Response (PR) After Dalotuzumab Plus Erlotinib Treatment (Objective Response Rate [ORR])	—	—	2.8 percentage of participants Interval 0.1 to 14.5	5.6 percentage of participants Interval 0.7 to 18.7

Adverse Events

Ph I: Dalotuzumab 5 mg/kg + Erlotinib

Serious events: 3 serious events

Other events: 4 other events

Deaths: 0 deaths

Ph I: Dalotuzumab 10 mg/kg + Erlotinib

Serious events: 4 serious events

Other events: 16 other events

Deaths: 0 deaths

Ph II: Dalotuzumab 10 mg/kg + Erlotinib

Serious events: 19 serious events

Other events: 37 other events

Deaths: 0 deaths

Ph II: Erlotinib

Serious events: 22 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ph I: Dalotuzumab 5 mg/kg + Erlotinib n=4 participants at risk During the Phase I part of the study, participants received dalotuzumab IV at 5 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who did not have disease progression and were satisfactorily tolerating study drug could continue to receive study drug.	Ph I: Dalotuzumab 10 mg/kg + Erlotinib n=16 participants at risk During the Phase I part of the study, participants received dalotuzumab IV at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who did not have disease progression and were satisfactorily tolerating study drug could continue to receive study drug.	Ph II: Dalotuzumab 10 mg/kg + Erlotinib n=37 participants at risk During the Phase II part of the study, participants were randomized to receive dalotuzumab IV at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.	Ph II: Erlotinib n=38 participants at risk During the Phase II part of the study, participants were randomized to receive open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.
Cardiac disorders Atrial fibrillation	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Diarrhoea	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	12.5% 2/16 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Gastritis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Melaena	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
General disorders Asthenia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
General disorders Chest pain	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
General disorders Fatigue	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Hepatobiliary disorders Bile duct obstruction	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Hepatobiliary disorders Bile duct stenosis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Infections and infestations Gastroenteritis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Infections and infestations Lymphangitis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Infections and infestations Pneumonia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	8.1% 3/37 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	10.5% 4/38 • Number of events 5 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Infections and infestations Respiratory tract infection	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Infections and infestations Sepsis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Infections and infestations Septic shock	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Overdose	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Investigations Blood creatinine increased	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Investigations Blood glucose increased	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Dehydration	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	21.6% 8/37 • Number of events 8 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	13.2% 5/38 • Number of events 6 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Nervous system disorders Balance disorder	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Nervous system disorders Cerebral haemorrhage	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Nervous system disorders Cerebral ischaemia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Nervous system disorders Spinal cord compression	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Skin disorder	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Vascular disorders Deep vein thrombosis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Vascular disorders Hypotension	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Vascular disorders Superior vena cava syndrome	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Vascular disorders Vasculitis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Vascular disorders Venous thrombosis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.

Other adverse events

Measure	Ph I: Dalotuzumab 5 mg/kg + Erlotinib n=4 participants at risk During the Phase I part of the study, participants received dalotuzumab IV at 5 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who did not have disease progression and were satisfactorily tolerating study drug could continue to receive study drug.	Ph I: Dalotuzumab 10 mg/kg + Erlotinib n=16 participants at risk During the Phase I part of the study, participants received dalotuzumab IV at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily for 4 weeks. After 4 weeks of therapy, participants in Phase I who did not have disease progression and were satisfactorily tolerating study drug could continue to receive study drug.	Ph II: Dalotuzumab 10 mg/kg + Erlotinib n=37 participants at risk During the Phase II part of the study, participants were randomized to receive dalotuzumab IV at 10 mg/kg weekly plus open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.	Ph II: Erlotinib n=38 participants at risk During the Phase II part of the study, participants were randomized to receive open-label erlotinib at 150 mg daily until disease progression or occurrence of unacceptable toxic effects.
Blood and lymphatic system disorders Anaemia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	12.5% 2/16 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	16.2% 6/37 • Number of events 6 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 13 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Cardiac disorders Tachycardia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Congenital, familial and genetic disorders Trichomegaly	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Ear and labyrinth disorders Vertigo	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Eye disorders Conjunctivitis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	8.1% 3/37 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	7.9% 3/38 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Eye disorders Lacrimation increased	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Eye disorders Ocular hyperaemia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Eye disorders Visual impairment	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal distension	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal pain	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	16.2% 6/37 • Number of events 9 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	15.8% 6/38 • Number of events 11 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	10.8% 4/37 • Number of events 6 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	10.5% 4/38 • Number of events 6 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Anal fissure	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Aphthous stomatitis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	12.5% 2/16 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Cheilitis	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Constipation	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	12.5% 2/16 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	32.4% 12/37 • Number of events 16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	26.3% 10/38 • Number of events 11 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Diarrhoea	25.0% 1/4 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	68.8% 11/16 • Number of events 49 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	81.1% 30/37 • Number of events 48 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	71.1% 27/38 • Number of events 75 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Dry mouth	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	18.8% 3/16 • Number of events 4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	8.1% 3/37 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	13.2% 5/38 • Number of events 5 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Dyspepsia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	13.2% 5/38 • Number of events 6 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Dysphagia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	12.5% 2/16 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Gastrooesophageal reflux disease	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Haemorrhoids	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Nausea	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	31.2% 5/16 • Number of events 5 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	45.9% 17/37 • Number of events 27 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	44.7% 17/38 • Number of events 23 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Odynophagia	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	12.5% 2/16 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Oral pain	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Stomatitis	50.0% 2/4 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	31.2% 5/16 • Number of events 7 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	10.8% 4/37 • Number of events 4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	7.9% 3/38 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Tooth loss	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Toothache	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Gastrointestinal disorders Vomiting	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	31.2% 5/16 • Number of events 7 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	18.9% 7/37 • Number of events 9 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	26.3% 10/38 • Number of events 16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
General disorders Asthenia	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	62.5% 10/16 • Number of events 16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	35.1% 13/37 • Number of events 20 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	34.2% 13/38 • Number of events 26 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
General disorders Chest pain	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	25.0% 4/16 • Number of events 4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	21.1% 8/38 • Number of events 9 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
General disorders Chills	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
General disorders Face oedema	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
General disorders Fatigue	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	12.5% 2/16 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	29.7% 11/37 • Number of events 15 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	34.2% 13/38 • Number of events 16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
General disorders Mucosal inflammation	75.0% 3/4 • Number of events 4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	12.5% 2/16 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	13.5% 5/37 • Number of events 6 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	7.9% 3/38 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
General disorders Oedema peripheral	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	13.2% 5/38 • Number of events 6 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
General disorders Pain	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	7.9% 3/38 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
General disorders Pyrexia	75.0% 3/4 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	31.2% 5/16 • Number of events 9 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	13.5% 5/37 • Number of events 9 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	15.8% 6/38 • Number of events 7 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
General disorders Visceral pain	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Infections and infestations Cystitis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 11 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Infections and infestations Dermatitis infected	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Infections and infestations Ecthyma	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Infections and infestations Febrile infection	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Infections and infestations Folliculitis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Infections and infestations Fungal infection	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Infections and infestations Herpes zoster	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Infections and infestations Influenza	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Infections and infestations Nasopharyngitis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	18.8% 3/16 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	7.9% 3/38 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Infections and infestations Oesophageal candidiasis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Infections and infestations Paronychia	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	16.2% 6/37 • Number of events 10 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	21.1% 8/38 • Number of events 10 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Infections and infestations Pharyngitis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Infections and infestations Respiratory tract infection	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	10.8% 4/37 • Number of events 7 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	10.5% 4/38 • Number of events 4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Infections and infestations Rhinitis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Infections and infestations Urinary tract infection	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Overdose	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	12.5% 2/16 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Investigations Blood amylase increased	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 5 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Investigations Blood creatinine increased	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	12.5% 2/16 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	7.9% 3/38 • Number of events 8 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Investigations Gamma-glutamyltransferase increased	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Investigations Weight decreased	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	13.5% 5/37 • Number of events 6 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	10.5% 4/38 • Number of events 4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Decreased appetite	50.0% 2/4 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	43.8% 7/16 • Number of events 11 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	59.5% 22/37 • Number of events 26 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	55.3% 21/38 • Number of events 26 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hyperamylasaemia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	12.5% 2/16 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hypercholesterolaemia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	43.8% 7/16 • Number of events 21 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	16.2% 6/37 • Number of events 8 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	13.2% 5/38 • Number of events 7 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hypertriglyceridaemia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	13.2% 5/38 • Number of events 6 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	13.2% 5/38 • Number of events 5 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	12.5% 2/16 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	8.1% 3/37 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	13.2% 5/38 • Number of events 7 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	12.5% 2/16 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 5 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	13.2% 5/38 • Number of events 6 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Groin pain	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Muscle contracture	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	12.5% 2/16 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	18.9% 7/37 • Number of events 9 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	10.8% 4/37 • Number of events 4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	7.9% 3/38 • Number of events 4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	12.5% 2/16 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	8.1% 3/37 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	10.5% 4/38 • Number of events 4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	10.5% 4/38 • Number of events 5 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Nervous system disorders Aphonia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Nervous system disorders Burning sensation	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Nervous system disorders Dizziness	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	13.5% 5/37 • Number of events 7 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	7.9% 3/38 • Number of events 5 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Nervous system disorders Dysaesthesia	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Nervous system disorders Dysarthria	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Nervous system disorders Dysgeusia	50.0% 2/4 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	18.8% 3/16 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	10.8% 4/37 • Number of events 4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	13.2% 5/38 • Number of events 6 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Nervous system disorders Headache	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	10.8% 4/37 • Number of events 4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	13.2% 5/38 • Number of events 5 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Nervous system disorders Neuropathy peripheral	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Nervous system disorders Paraesthesia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	12.5% 2/16 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	8.1% 3/37 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	10.5% 4/38 • Number of events 4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Nervous system disorders Somnolence	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Psychiatric disorders Anxiety	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	12.5% 2/16 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Psychiatric disorders Depression	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Psychiatric disorders Insomnia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	10.5% 4/38 • Number of events 4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Renal and urinary disorders Bladder spasm	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Renal and urinary disorders Dysuria	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	12.5% 2/16 • Number of events 5 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Renal and urinary disorders Haematuria	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Renal and urinary disorders Micturition disorder	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Renal and urinary disorders Nephrolithiasis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Renal and urinary disorders Nephropathy toxic	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Reproductive system and breast disorders Sexual dysfunction	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Reproductive system and breast disorders Vulvovaginal dryness	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	18.8% 3/16 • Number of events 4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	18.9% 7/37 • Number of events 8 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	18.4% 7/38 • Number of events 8 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	37.5% 6/16 • Number of events 8 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	13.5% 5/37 • Number of events 5 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	31.6% 12/38 • Number of events 15 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	10.8% 4/37 • Number of events 5 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	10.5% 4/38 • Number of events 5 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	18.8% 3/16 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	8.1% 3/37 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	10.5% 4/38 • Number of events 7 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	7.9% 3/38 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Productive cough	50.0% 2/4 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	12.5% 2/16 • Number of events 4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	18.8% 3/16 • Number of events 4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	8.1% 3/37 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Sneezing	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Acne	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	12.5% 2/16 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	7.9% 3/38 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Dermatitis acneiform	50.0% 2/4 • Number of events 12 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	37.5% 6/16 • Number of events 12 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	8.1% 3/37 • Number of events 4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	21.1% 8/38 • Number of events 13 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	18.8% 3/16 • Number of events 5 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	24.3% 9/37 • Number of events 9 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	18.4% 7/38 • Number of events 10 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 5 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	10.5% 4/38 • Number of events 6 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Hirsutism	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Hypertrichosis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Nail disorder	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	8.1% 3/37 • Number of events 4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Onychoclasis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	12.5% 2/16 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	7.9% 3/38 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Petechiae	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	25.0% 4/16 • Number of events 6 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	18.9% 7/37 • Number of events 10 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	28.9% 11/38 • Number of events 11 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Pruritus generalised	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	12.5% 2/16 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Purpura	25.0% 1/4 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Rash	25.0% 1/4 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	50.0% 8/16 • Number of events 13 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	75.7% 28/37 • Number of events 45 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	57.9% 22/38 • Number of events 39 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Rash generalised	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Scab	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.6% 1/38 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	6.2% 1/16 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/38 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Xeroderma	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	25.0% 4/16 • Number of events 6 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	18.4% 7/38 • Number of events 8 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Vascular disorders Deep vein thrombosis	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	2.7% 1/37 • Number of events 1 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Vascular disorders Hot flush	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 3 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Vascular disorders Hypertension	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/37 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.
Vascular disorders Hypotension	0.00% 0/4 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	0.00% 0/16 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.4% 2/37 • Number of events 2 • Up to 47 months All Participants as Treated (APaT) population; all allocated participants who received at least one dose of study treatment.	5.3% 2/38 • Number of events 5 • Up to 47 months All Participants as Treated (APaT) population; all allocated 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: ClinicalTrialsDisclosure@merck.com

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.
• Publication restrictions are in place

Restriction type: OTHER