Trial Outcomes & Findings for A Study of Pertuzumab in Combination With Trastuzumab and Chemotherapy in Patients With HER2-Positive Advanced Gastric Cancer (NCT NCT01461057)

NCT ID: NCT01461057

Last Updated: 2018-08-09

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 30 participants
• Primary outcome timeframe: Day 43
• Results posted on: 2018-08-09

Participant Flow

Participant milestones

Measure	Pertuzumab 840/420 mg Participants received pertuzumab as an intravenous (IV) infusion at a loading dose of 840 milligrams (mg) for cycle 1 and a dose of 420 mg every three weeks (Q3W) for cycles 2-6. Participants in both arms received trastuzumab, cisplatin, and capecitabine. Capecitabine 1000 milligram per meter squared (mg/m\^2) was administered orally twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle. Cisplatin 80 mg/m\^2 was administered as an IV infusion on Day 1 of each cycle. Trastuzumab was administered as an IV infusion at a loading dose of 8 mg/kg for Cycle 1 and a dose of 6 milligram per kilogram (mg/kg) Q3W for subsequent cycles.	Pertuzumab 840/840 mg Participants received 840 mg as an IV infusion Q3W for cycles 1-6. Participants in both arms received trastuzumab, cisplatin, and capecitabine. Capecitabine 1000 mg/m\^2 was administered orally twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle. Cisplatin 80 mg/m\^2 was administered as an IV infusion on Day 1 of each cycle. Trastuzumab was administered as an IV infusion at a loading dose of 8 mg/kg for Cycle 1 and a dose of 6 mg/kg Q3W for subsequent cycles.
Overall Study STARTED	15	15
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	15	15

Reasons for withdrawal

Measure	Pertuzumab 840/420 mg Participants received pertuzumab as an intravenous (IV) infusion at a loading dose of 840 milligrams (mg) for cycle 1 and a dose of 420 mg every three weeks (Q3W) for cycles 2-6. Participants in both arms received trastuzumab, cisplatin, and capecitabine. Capecitabine 1000 milligram per meter squared (mg/m\^2) was administered orally twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle. Cisplatin 80 mg/m\^2 was administered as an IV infusion on Day 1 of each cycle. Trastuzumab was administered as an IV infusion at a loading dose of 8 mg/kg for Cycle 1 and a dose of 6 milligram per kilogram (mg/kg) Q3W for subsequent cycles.	Pertuzumab 840/840 mg Participants received 840 mg as an IV infusion Q3W for cycles 1-6. Participants in both arms received trastuzumab, cisplatin, and capecitabine. Capecitabine 1000 mg/m\^2 was administered orally twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle. Cisplatin 80 mg/m\^2 was administered as an IV infusion on Day 1 of each cycle. Trastuzumab was administered as an IV infusion at a loading dose of 8 mg/kg for Cycle 1 and a dose of 6 mg/kg Q3W for subsequent cycles.
Overall Study Death	10	9
Overall Study Withdrawal by Subject	2	3
Overall Study Physician Decision	0	2
Overall Study Adverse Event	0	1
Overall Study Progression of Disease	1	0
Overall Study Study Terminated by Sponsor	2	0

Baseline Characteristics

A Study of Pertuzumab in Combination With Trastuzumab and Chemotherapy in Patients With HER2-Positive Advanced Gastric Cancer

Baseline characteristics by cohort

Measure	Pertuzumab 840/420 mg n=15 Participants Participants received pertuzumab as an intravenous (IV) infusion at a loading dose of 840 milligrams (mg) for cycle 1 and a dose of 420 mg every three weeks (Q3W) for cycles 2-6. Participants in both arms received trastuzumab, cisplatin, and capecitabine. Capecitabine 1000 milligram per meter squared (mg/m\^2) was administered orally twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle. Cisplatin 80 mg/m\^2 was administered as an IV infusion on Day 1 of each cycle. Trastuzumab was administered as an IV infusion at a loading dose of 8 mg/kg for Cycle 1 and a dose of 6 milligram per kilogram (mg/kg) Q3W for subsequent cycles.	Pertuzumab 840/840 mg n=15 Participants Participants received 840 mg as an IV infusion Q3W for cycles 1-6. Participants in both arms received trastuzumab, cisplatin, and capecitabine. Capecitabine 1000 mg/m\^2 was administered orally twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle. Cisplatin 80 mg/m\^2 was administered as an IV infusion on Day 1 of each cycle. Trastuzumab was administered as an IV infusion at a loading dose of 8 mg/kg for Cycle 1 and a dose of 6 mg/kg Q3W for subsequent cycles.	Total n=30 Participants Total of all reporting groups
Age, Customized 18 - 40 years	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Age, Customized 41 - 64 years	4 Participants n=5 Participants	9 Participants n=7 Participants	13 Participants n=5 Participants
Age, Customized Greater than or equal to (>=) 65 years	9 Participants n=5 Participants	5 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	10 Participants n=7 Participants	24 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 43

Population: The primary pharmacokinetic (PK) analysis population consisted of all participants with a measurable PK samples on Day 43.

Outcome measures

Measure	Pertuzumab 840/420 mg n=15 Participants Participants received pertuzumab as an intravenous (IV) infusion at a loading dose of 840 milligrams (mg) for cycle 1 and a dose of 420 mg every three weeks (Q3W) for cycles 2-6. Participants in both arms received trastuzumab, cisplatin, and capecitabine. Capecitabine 1000 milligram per meter squared (mg/m\^2) was administered orally twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle. Cisplatin 80 mg/m\^2 was administered as an IV infusion on Day 1 of each cycle. Trastuzumab was administered as an IV infusion at a loading dose of 8 mg/kg for Cycle 1 and a dose of 6 milligram per kilogram (mg/kg) Q3W for subsequent cycles.	Pertuzumab 840/840 mg n=12 Participants Participants received 840 mg as an IV infusion Q3W for cycles 1-6. Participants in both arms received trastuzumab, cisplatin, and capecitabine. Capecitabine 1000 mg/m\^2 was administered orally twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle. Cisplatin 80 mg/m\^2 was administered as an IV infusion on Day 1 of each cycle. Trastuzumab was administered as an IV infusion at a loading dose of 8 mg/kg for Cycle 1 and a dose of 6 mg/kg Q3W for subsequent cycles.
Percentage of Participants With Day 43 Serum Pertuzumab Trough Concentrations (Cmin) Greater Than or Equal to (>=) 20 Microgram Per Milliliter (mcg/mL)	91.6 percentage of participants Interval 78.3 to 99.2	98.3 percentage of participants Interval 91.4 to 99.97

PRIMARY outcome

Timeframe: From randomization of first participant to end of study (approximately 6 years)

Population: Safety population included all participants who received at least one dose of study treatment.

An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.

Outcome measures

Measure	Pertuzumab 840/420 mg n=15 Participants Participants received pertuzumab as an intravenous (IV) infusion at a loading dose of 840 milligrams (mg) for cycle 1 and a dose of 420 mg every three weeks (Q3W) for cycles 2-6. Participants in both arms received trastuzumab, cisplatin, and capecitabine. Capecitabine 1000 milligram per meter squared (mg/m\^2) was administered orally twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle. Cisplatin 80 mg/m\^2 was administered as an IV infusion on Day 1 of each cycle. Trastuzumab was administered as an IV infusion at a loading dose of 8 mg/kg for Cycle 1 and a dose of 6 milligram per kilogram (mg/kg) Q3W for subsequent cycles.	Pertuzumab 840/840 mg n=15 Participants Participants received 840 mg as an IV infusion Q3W for cycles 1-6. Participants in both arms received trastuzumab, cisplatin, and capecitabine. Capecitabine 1000 mg/m\^2 was administered orally twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle. Cisplatin 80 mg/m\^2 was administered as an IV infusion on Day 1 of each cycle. Trastuzumab was administered as an IV infusion at a loading dose of 8 mg/kg for Cycle 1 and a dose of 6 mg/kg Q3W for subsequent cycles.
Number of Participants With Adverse Events (AEs)	15 participants	15 participants

Adverse Events

Pertuzumab 840/420 mg

Serious events: 11 serious events

Other events: 15 other events

Deaths: 10 deaths

Pertuzumab 840/840 mg

Serious events: 10 serious events

Other events: 15 other events

Deaths: 9 deaths

Serious adverse events

Measure	Pertuzumab 840/420 mg n=15 participants at risk Participants received pertuzumab as an intravenous (IV) infusion at a loading dose of 840 milligrams (mg) for cycle 1 and a dose of 420 mg every three weeks (Q3W) for cycles 2-6. Participants in both arms received trastuzumab, cisplatin, and capecitabine. Capecitabine 1000 milligram per meter squared (mg/m\^2) was administered orally twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle. Cisplatin 80 mg/m\^2 was administered as an IV infusion on Day 1 of each cycle. Trastuzumab was administered as an IV infusion at a loading dose of 8 mg/kg for Cycle 1 and a dose of 6 milligram per kilogram (mg/kg) Q3W for subsequent cycles.	Pertuzumab 840/840 mg n=15 participants at risk Participants received 840 mg as an IV infusion Q3W for cycles 1-6. Participants in both arms received trastuzumab, cisplatin, and capecitabine. Capecitabine 1000 mg/m\^2 was administered orally twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle. Cisplatin 80 mg/m\^2 was administered as an IV infusion on Day 1 of each cycle. Trastuzumab was administered as an IV infusion at a loading dose of 8 mg/kg for Cycle 1 and a dose of 6 mg/kg Q3W for subsequent cycles.
Blood and lymphatic system disorders Febrile neutropenia	26.7% 4/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Cardiac disorders Cardiac failure acute	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Ascites	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Diarrhoea	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	20.0% 3/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Dyspepsia	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Gastric haemorrhage	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Ileus	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Nausea	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Obstruction gastric	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Vomiting	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
General disorders Asthenia	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
General disorders Fatigue	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
General disorders Mucosal inflammation	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
General disorders Pyrexia	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Hepatobiliary disorders Cholecystitis	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Biliary sepsis	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Biliary tract infection	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Erysipelas	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Herpes zoster	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Peritonitis	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Pneumonia	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Pneumonia fungal	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Injury, poisoning and procedural complications Accident	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Ejection fraction decreased	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Myoglobin blood increased	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Neutrophil count decreased	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Platelet count decreased	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Metabolism and nutrition disorders Food intolerance	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Metabolism and nutrition disorders Hyponatraemia	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Nervous system disorders Cerebrovascular accident	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Nervous system disorders Dizziness	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Renal and urinary disorders Azotaemia	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Renal and urinary disorders Renal failure	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Renal and urinary disorders Acute kidney injury	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Vascular disorders Embolism	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.

Other adverse events

Measure	Pertuzumab 840/420 mg n=15 participants at risk Participants received pertuzumab as an intravenous (IV) infusion at a loading dose of 840 milligrams (mg) for cycle 1 and a dose of 420 mg every three weeks (Q3W) for cycles 2-6. Participants in both arms received trastuzumab, cisplatin, and capecitabine. Capecitabine 1000 milligram per meter squared (mg/m\^2) was administered orally twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle. Cisplatin 80 mg/m\^2 was administered as an IV infusion on Day 1 of each cycle. Trastuzumab was administered as an IV infusion at a loading dose of 8 mg/kg for Cycle 1 and a dose of 6 milligram per kilogram (mg/kg) Q3W for subsequent cycles.	Pertuzumab 840/840 mg n=15 participants at risk Participants received 840 mg as an IV infusion Q3W for cycles 1-6. Participants in both arms received trastuzumab, cisplatin, and capecitabine. Capecitabine 1000 mg/m\^2 was administered orally twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle. Cisplatin 80 mg/m\^2 was administered as an IV infusion on Day 1 of each cycle. Trastuzumab was administered as an IV infusion at a loading dose of 8 mg/kg for Cycle 1 and a dose of 6 mg/kg Q3W for subsequent cycles.
Blood and lymphatic system disorders Anaemia	60.0% 9/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	73.3% 11/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Blood and lymphatic system disorders Febrile Neutropenia	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Blood and lymphatic system disorders Leukocytosis	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Blood and lymphatic system disorders Leukopenia	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Blood and lymphatic system disorders Neutrophilia	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Blood and lymphatic system disorders Thrombocytopenia	20.0% 3/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Cardiac disorders Cardiomyopathy	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Ear and labyrinth disorders Tinnitus	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Endocrine disorders Hyperthyroidism	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Eye disorders Dry eye	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Eye disorders Lacrimation increased	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Abdominal pain	33.3% 5/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	33.3% 5/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Abdominal pain upper	26.7% 4/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Ascites	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Cheilitis	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Colitis	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Constipation	20.0% 3/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Diarrhoea	93.3% 14/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	73.3% 11/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Dry mouth	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Dyspepsia	20.0% 3/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	33.3% 5/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Enteritis	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Eructation	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Gastric ulcer	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Gastrointestinal pain	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Ileus	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Nausea	73.3% 11/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	86.7% 13/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Oesophagitis	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Pancreatitis	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Stomatits	60.0% 9/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	40.0% 6/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Tooth loss	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Vomiting	60.0% 9/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	20.0% 3/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Gastrointestinal disorders Dysphagia	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
General disorders Adverse drug reaction	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
General disorders Asthenia	40.0% 6/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	20.0% 3/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
General disorders Catheter site pain	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
General disorders Chest pain	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
General disorders Chills	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
General disorders Face oedema	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
General disorders Fatigue	33.3% 5/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	46.7% 7/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
General disorders General physical health deterioration	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
General disorders Influenza like illness	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
General disorders Injection site reaction	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
General disorders Mucosal inflammation	26.7% 4/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
General disorders Oedema peripheral	33.3% 5/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	26.7% 4/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
General disorders Pain	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	20.0% 3/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
General disorders Pyrexia	40.0% 6/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
General disorders Xerosis	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Hepatobiliary disorders Cholelithiasis	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Hepatobiliary disorders Hyperbilirubinaemia	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Immune system disorders Drug hypersensitivity	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Bronchitis	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Cellulitis	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Cystitis	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Gingivitis	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Hepatitis B	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Herpes Simplex	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Herpes virus infection	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Nasopharyngitis	20.0% 3/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Oral herpes	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Paronychia	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Pneumonia	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Tinea versicolour	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Toxocariasis	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Upper respiratory tract infection	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Urinary tract infection	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Infections and infestations Vaginal infection	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Injury, poisoning and procedural complications Allergic transfusion reaction	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Injury, poisoning and procedural complications Contusion	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Injury, poisoning and procedural complications Infusion related reaction	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Activated partial thromboplastin time prolonged	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Alanine aminotransferase increased	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	20.0% 3/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Amylase increased	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Aspartate aminotransferase inreased	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Bilirubin conjugated increased	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Blood bilirubin increased	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Blood cholesterol increased	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Blood cholinesterase decreased	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Blood creatine phosphokinase increased	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Blood creatine phosphokinase MB increased	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Blood creatinine increased	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Blood fibrinogen increased	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Blood iron increased	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Blood lactate dehydrogenase increased	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Blood potassium increased	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Blood urea increased	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Creatinine renal clearance decreased	26.7% 4/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Ejection fraction decreased	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Fibrin D dimer increased	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Gamma-glutamyltransferase increased	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Glomerular filtration rate decreased	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations International normalised ratio increased	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Lipase increased	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Neutrophil count decreased	73.3% 11/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	73.3% 11/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Platelet count decreased	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Protein total decreased	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Prothrombin time shortened	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Transaminases increased	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Weight decreased	26.7% 4/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	26.7% 4/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Weight increased	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations White blood cell count decreased	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Metabolism and nutrition disorders Decreased appetite	73.3% 11/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	60.0% 9/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Metabolism and nutrition disorders Hyperglycaemia	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Metabolism and nutrition disorders Hyperkalaemia	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Metabolism and nutrition disorders Hyperphosphataemia	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Metabolism and nutrition disorders Hypoalbuminaemia	26.7% 4/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Metabolism and nutrition disorders Hypocalcaemia	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Metabolism and nutrition disorders Hypochloraemia	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Metabolism and nutrition disorders Hypokalaemia	20.0% 3/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	40.0% 6/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Metabolism and nutrition disorders Hypomagnesaemia	53.3% 8/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	20.0% 3/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Metabolism and nutrition disorders Hyponatraemia	26.7% 4/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Metabolism and nutrition disorders Hypophosphataemia	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	20.0% 3/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Metabolism and nutrition disorders Hyposideraemia	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Metabolism and nutrition disorders Hypovitaminosis	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Musculoskeletal and connective tissue disorders Fracture pain	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Musculoskeletal and connective tissue disorders Muscle spasms	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Musculoskeletal and connective tissue disorders Muscular weakness	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	20.0% 3/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Musculoskeletal and connective tissue disorders Myalgia	26.7% 4/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Nervous system disorders Ageusia	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Nervous system disorders Cholinergic syndrome	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Nervous system disorders Dizziness	53.3% 8/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	20.0% 3/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Nervous system disorders Dysgeusia	20.0% 3/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	20.0% 3/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Nervous system disorders Headache	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Nervous system disorders Neuropathy peripheral	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Nervous system disorders Neurotoxicity	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Nervous system disorders Paraesthesia	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Nervous system disorders Peripheral sensory neuropathy	26.7% 4/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	26.7% 4/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Nervous system disorders Polyneuropathy	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Nervous system disorders Tension headache	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Nervous system disorders Tremor	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Psychiatric disorders Affective disorder	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Psychiatric disorders Anxiety	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Psychiatric disorders Insomnia	26.7% 4/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Psychiatric disorders Sleep disorder	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Psychiatric disorders Somatic symptom disorder	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Renal and urinary disorders Acute prerenal failure	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Renal and urinary disorders Azotaemia	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Renal and urinary disorders Haematuria	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Renal and urinary disorders Pollakiuria	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Renal and urinary disorders Renal failure	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Renal and urinary disorders Acute kidney injury	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Renal and urinary disorders Chronic kidney disease	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Reproductive system and breast disorders Benign prostatic hyperplasia	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Respiratory, thoracic and mediastinal disorders Cough	26.7% 4/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	20.0% 3/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	20.0% 3/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Respiratory, thoracic and mediastinal disorders Hiccups	33.3% 5/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	13.3% 2/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Respiratory, thoracic and mediastinal disorders Productive cough	40.0% 6/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Respiratory, thoracic and mediastinal disorders Rales	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	20.0% 3/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	26.7% 4/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Skin and subcutaneous tissue disorders Decubitus ulcer	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Skin and subcutaneous tissue disorders Dermatitis allergic	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Skin and subcutaneous tissue disorders Hyperhidrosis	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Skin and subcutaneous tissue disorders Nail ridging	20.0% 3/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Skin and subcutaneous tissue disorders Onycholysis	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Skin and subcutaneous tissue disorders Onychomadesis	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	33.3% 5/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	33.3% 5/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Skin and subcutaneous tissue disorders Pruritus	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Skin and subcutaneous tissue disorders Rash	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	33.3% 5/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	20.0% 3/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Skin and subcutaneous tissue disorders Stasis dermatitis	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Vascular disorders Deep vein thrombosis	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Vascular disorders Embolism	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Vascular disorders Flushing	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Vascular disorders Hypertension	26.7% 4/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Vascular disorders Hypertensive crisis	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Vascular disorders Hypotension	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Vascular disorders Subclavian vein thrombosis	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Eye disorders Glaucoma	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Urine output decreased	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Investigations Vitamin D decreased	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.
Respiratory, thoracic and mediastinal disorders Nasal inflammation	0.00% 0/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.	6.7% 1/15 • From randomization of first participant to end of study (approximately 6 years) An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER