Trial Outcomes & Findings for A Study to Evaluate rhuMab 2C4 and Gemcitabine in Subjects With Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (NCT NCT00096993)

NCT ID: NCT00096993

Last Updated: 2015-06-10

Results Overview

Progression-free survival was defined as the time from the first day of treatment (Cycle 1, Day 1) to the time of documented disease progression or death, whichever occurred first. Disease progression was assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR) was defined as disappearance of all target lesions; Partial Response (PR) was defined as \>=30% decrease in the sum of the longest diameter of target lesions and Overall Response (OR) = CR + PR.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 131 participants
• Primary outcome timeframe: Baseline to the end of the study (up to 1 year)
• Results posted on: 2015-06-10

Participant Flow

One subject in the placebo + gemcitabine arm did not receive any study treatment as the subject died of a cerebrovascular accident prior to the first scheduled dose. This subject was excluded from both the efficacy and safety analyses, per protocol.

Participant milestones

Measure	Placebo + Gemcitabine Participants received placebo intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Placebo: Placebo was provided as a single-use formulation for infusion. Gemcitabine: Gemcitabine was provided as a solution for infusion.	Pertuzumab + Gemcitabine Participants received pertuzumab intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Participants received pertuzumab at a loading dose of 840 mg in Cycle 1 followed by a dose of 420 mg in Cycles 2 and beyond. In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles Gemcitabine: Gemcitabine was provided as a solution for infusion. Pertuzumab: Pertuzumab was provided as a single-use formulation for infusion.
Overall Study STARTED	66	65
Overall Study COMPLETED	1	0
Overall Study NOT COMPLETED	65	65

Reasons for withdrawal

Measure	Placebo + Gemcitabine Participants received placebo intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Placebo: Placebo was provided as a single-use formulation for infusion. Gemcitabine: Gemcitabine was provided as a solution for infusion.	Pertuzumab + Gemcitabine Participants received pertuzumab intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Participants received pertuzumab at a loading dose of 840 mg in Cycle 1 followed by a dose of 420 mg in Cycles 2 and beyond. In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles Gemcitabine: Gemcitabine was provided as a solution for infusion. Pertuzumab: Pertuzumab was provided as a single-use formulation for infusion.
Overall Study Death	1	0
Overall Study Disease progression	56	53
Overall Study Adverse Event	2	8
Overall Study Subject's decision	3	1
Overall Study Physician Decision	2	1
Overall Study Non-compliance	0	1
Overall Study Other unspecified	1	1

Baseline Characteristics

A Study to Evaluate rhuMab 2C4 and Gemcitabine in Subjects With Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Baseline characteristics by cohort

Measure	Placebo + Gemcitabine n=65 Participants Participants received placebo intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Placebo: Placebo was provided as a single-use formulation for infusion. Gemcitabine: Gemcitabine was provided as a solution for infusion.	Pertuzumab + Gemcitabine n=65 Participants Participants received pertuzumab intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Participants received pertuzumab at a loading dose of 840 mg in Cycle 1 followed by a dose of 420 mg in Cycles 2 and beyond. In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles Gemcitabine: Gemcitabine was provided as a solution for infusion. Pertuzumab: Pertuzumab was provided as a single-use formulation for infusion.	Total n=130 Participants Total of all reporting groups
Age, Continuous	59.7 years STANDARD_DEVIATION 11.94 • n=5 Participants	57.8 years STANDARD_DEVIATION 10.79 • n=7 Participants	58.7 years STANDARD_DEVIATION 11.38 • n=5 Participants
Sex: Female, Male Female	65 Participants n=5 Participants	65 Participants n=7 Participants	130 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to the end of the study (up to 1 year)

Population: Efficacy-evaluable population: All randomized participants who received at least 1 dose of study medication.

Progression-free survival was defined as the time from the first day of treatment (Cycle 1, Day 1) to the time of documented disease progression or death, whichever occurred first. Disease progression was assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR) was defined as disappearance of all target lesions; Partial Response (PR) was defined as >=30% decrease in the sum of the longest diameter of target lesions and Overall Response (OR) = CR + PR.

Outcome measures

Measure	Placebo + Gemcitabine n=54 Participants Participants received placebo intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Placebo: Placebo was provided as a single-use formulation for infusion. Gemcitabine: Gemcitabine was provided as a solution for infusion.	Pertuzumab + Gemcitabine n=49 Participants Participants received pertuzumab intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Participants received pertuzumab at a loading dose of 840 mg in Cycle 1 followed by a dose of 420 mg in Cycles 2 and beyond. In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles Gemcitabine: Gemcitabine was provided as a solution for infusion. Pertuzumab: Pertuzumab was provided as a single-use formulation for infusion.
Progression-free Survival	2.6 months Interval 1.4 to 3.9	2.9 months Interval 2.6 to 4.4

SECONDARY outcome

Timeframe: Baseline to the end of the study (up to 1 year)

Population: Efficacy-evaluable population: All randomized participants who received at least 1 dose of study medication.

An objective response was defined as a complete or partial response determined on two consecutive occasions ≥ 4 weeks apart. Responses were determined by Response Evaluation Criteria in Solid Tumors (RECIST). A complete response was defined as the disappearance of all target lesions or the disappearance of all non-target lesions and normalization of tumor marker level. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter of target lesions.

Outcome measures

Measure	Placebo + Gemcitabine n=65 Participants Participants received placebo intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Placebo: Placebo was provided as a single-use formulation for infusion. Gemcitabine: Gemcitabine was provided as a solution for infusion.	Pertuzumab + Gemcitabine n=65 Participants Participants received pertuzumab intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Participants received pertuzumab at a loading dose of 840 mg in Cycle 1 followed by a dose of 420 mg in Cycles 2 and beyond. In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles Gemcitabine: Gemcitabine was provided as a solution for infusion. Pertuzumab: Pertuzumab was provided as a single-use formulation for infusion.
Percentage of Participants With an Objective Response	4.6 percentage of participants	13.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline to the end of the study (up to 1 year)

Population: Efficacy-evaluable population: All randomized participants who received at least 1 dose of study medication. Only participants with an objective response were included in the analysis.

Duration of the objective response was defined as the time from the initial response to disease progression or death from any cause.

Outcome measures

Measure	Placebo + Gemcitabine n=3 Participants Participants received placebo intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Placebo: Placebo was provided as a single-use formulation for infusion. Gemcitabine: Gemcitabine was provided as a solution for infusion.	Pertuzumab + Gemcitabine n=9 Participants Participants received pertuzumab intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Participants received pertuzumab at a loading dose of 840 mg in Cycle 1 followed by a dose of 420 mg in Cycles 2 and beyond. In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles Gemcitabine: Gemcitabine was provided as a solution for infusion. Pertuzumab: Pertuzumab was provided as a single-use formulation for infusion.
Duration of the Objective Response	NA months Interval 4.1 to Value is not estimable; not reached	6.9 months Interval 4.1 to 7.4

SECONDARY outcome

Timeframe: Baseline to Month 4

Population: Efficacy-evaluable population: All randomized participants who received at least 1 dose of study medication.

Disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.

Outcome measures

Measure	Placebo + Gemcitabine n=65 Participants Participants received placebo intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Placebo: Placebo was provided as a single-use formulation for infusion. Gemcitabine: Gemcitabine was provided as a solution for infusion.	Pertuzumab + Gemcitabine n=65 Participants Participants received pertuzumab intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Participants received pertuzumab at a loading dose of 840 mg in Cycle 1 followed by a dose of 420 mg in Cycles 2 and beyond. In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles Gemcitabine: Gemcitabine was provided as a solution for infusion. Pertuzumab: Pertuzumab was provided as a single-use formulation for infusion.
Percentage of Participants Free From Disease Progression at 4 Months	37.3 percentage of participants	47.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline to the end of the study (up to 1 year)

Population: Efficacy-evaluable population: All randomized participants who received at least 1 dose of study medication.

Duration of survival was defined as the time from randomization until death from any cause.

Outcome measures

Measure	Placebo + Gemcitabine n=65 Participants Participants received placebo intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Placebo: Placebo was provided as a single-use formulation for infusion. Gemcitabine: Gemcitabine was provided as a solution for infusion.	Pertuzumab + Gemcitabine n=65 Participants Participants received pertuzumab intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Participants received pertuzumab at a loading dose of 840 mg in Cycle 1 followed by a dose of 420 mg in Cycles 2 and beyond. In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles Gemcitabine: Gemcitabine was provided as a solution for infusion. Pertuzumab: Pertuzumab was provided as a single-use formulation for infusion.
Duration of Survival	13.1 months Interval 10.5 to 15.5	13.0 months Interval 9.6 to 18.5

Adverse Events

Placebo + Gemcitabine

Serious events: 40 serious events

Other events: 65 other events

Deaths: 0 deaths

Pertuzumab + Gemcitabine

Serious events: 23 serious events

Other events: 65 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo + Gemcitabine n=65 participants at risk Participants received placebo intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Placebo: Placebo was provided as a single-use formulation for infusion. Gemcitabine: Gemcitabine was provided as a solution for infusion.	Pertuzumab + Gemcitabine n=65 participants at risk Participants received pertuzumab intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Participants received pertuzumab at a loading dose of 840 mg in Cycle 1 followed by a dose of 420 mg in Cycles 2 and beyond. In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles Gemcitabine: Gemcitabine was provided as a solution for infusion. Pertuzumab: Pertuzumab was provided as a single-use formulation for infusion.
Gastrointestinal disorders SMALL INTESTINAL OBSTRUCTION	12.3% 8/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	3.1% 2/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders VOMITING	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders ILEUS	3.1% 2/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders INTESTINAL OBSTRUCTION	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders ABDOMINAL PAIN	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	3.1% 2/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders NAUSEA	3.1% 2/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders COLONIC STENOSIS	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders CONSTIPATION	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders UPPER GASTROINTESTINAL HAEMORRHAGE	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	3.1% 2/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	3.1% 2/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Respiratory, thoracic and mediastinal disorders PULMONARY EMBOLISM	3.1% 2/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Respiratory, thoracic and mediastinal disorders PNEUMONIA ASPIRATION	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Respiratory, thoracic and mediastinal disorders PNEUMONITIS	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Respiratory, thoracic and mediastinal disorders PNEUMOTHORAX	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Respiratory, thoracic and mediastinal disorders PULMONARY FIBROSIS	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Respiratory, thoracic and mediastinal disorders PULMONARY OEDEMA	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Respiratory, thoracic and mediastinal disorders RESPIRATORY ARREST	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Respiratory, thoracic and mediastinal disorders RESPIRATORY FAILURE	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Infections and infestations PNEUMONIA	3.1% 2/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Infections and infestations CELLULITIS	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Infections and infestations INFECTION	3.1% 2/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Infections and infestations CATHETER RELATED INFECTION	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Infections and infestations CLOSTRIDIAL INFECTION	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Infections and infestations CLOSTRIDIUM DIFFICILE COLITIS	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Infections and infestations SEPSIS	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Infections and infestations STAPHYLOCOCCAL INFECTION	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Infections and infestations URINARY TRACT INFECTION	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Vascular disorders DEEP VEIN THROMBOSIS	3.1% 2/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	3.1% 2/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Vascular disorders HYPOTENSION	3.1% 2/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Vascular disorders HYPERTENSION	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Vascular disorders THROMBOSIS	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
General disorders CHEST PAIN	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
General disorders CATHETER RELATED COMPLICATION	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
General disorders FATIGUE	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
General disorders INFUSION RELATED REACTION	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
General disorders PYREXIA	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Renal and urinary disorders RENAL FAILURE ACUTE	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Renal and urinary disorders HAEMATURIA	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Renal and urinary disorders URETERIC OBSTRUCTION	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Blood and lymphatic system disorders FEBRILE NEUTROPENIA	3.1% 2/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Blood and lymphatic system disorders THROMBOCYTOPENIA	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	3.1% 2/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Blood and lymphatic system disorders ANAEMIA	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Blood and lymphatic system disorders HAEMOLYTIC URAEMIC SYNDROME	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Metabolism and nutrition disorders DEHYDRATION	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Metabolism and nutrition disorders HYPONATRAEMIA	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Psychiatric disorders CONFUSIONAL STATE	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Psychiatric disorders MENTAL STATUS CHANGES	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Immune system disorders ANAPHYLACTIC REACTION	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Immune system disorders HYPERSENSITIVITY	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Cardiac disorders CARDIAC FAILURE CONGESTIVE	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Hepatobiliary disorders CHOLECYSTITIS	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Injury, poisoning and procedural complications FEEDING TUBE COMPLICATION	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) MALIGNANT MELANOMA	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Nervous system disorders DIZZINESS	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Skin and subcutaneous tissue disorders DERMATOMYOSITIS	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.

Other adverse events

Measure	Placebo + Gemcitabine n=65 participants at risk Participants received placebo intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Placebo: Placebo was provided as a single-use formulation for infusion. Gemcitabine: Gemcitabine was provided as a solution for infusion.	Pertuzumab + Gemcitabine n=65 participants at risk Participants received pertuzumab intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Participants received pertuzumab at a loading dose of 840 mg in Cycle 1 followed by a dose of 420 mg in Cycles 2 and beyond. In addition, participants received gemcitabine 800 mg/m\^2 intravenously on Days 1 and 8 of every 3 week cycle for up to 1 year (up to 17 treatment cycles Gemcitabine: Gemcitabine was provided as a solution for infusion. Pertuzumab: Pertuzumab was provided as a single-use formulation for infusion.
Gastrointestinal disorders NAUSEA	72.3% 47/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	75.4% 49/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders DIARRHOEA	60.0% 39/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	67.7% 44/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders VOMITING	50.8% 33/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	49.2% 32/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders CONSTIPATION	61.5% 40/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	20.0% 13/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders ABDOMINAL PAIN	40.0% 26/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	33.8% 22/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders ABDOMINAL DISTENSION	32.3% 21/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	18.5% 12/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders STOMATITIS	16.9% 11/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	29.2% 19/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders DYSPEPSIA	20.0% 13/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	21.5% 14/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders ABDOMINAL PAIN UPPER	20.0% 13/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	9.2% 6/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders GASTROOESOPHAGEAL REFLUX DISEASE	15.4% 10/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	13.8% 9/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders ABDOMINAL DISCOMFORT	12.3% 8/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders ABDOMINAL PAIN LOWER	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	10.8% 7/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders ASCITES	13.8% 9/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders DRY MOUTH	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	3.1% 2/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders FLATULENCE	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders ORAL PAIN	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	3.1% 2/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Gastrointestinal disorders RECTAL HAEMORRHAGE	3.1% 2/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
General disorders FATIGUE	76.9% 50/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	78.5% 51/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
General disorders OEDEMA PERIPHERAL	43.1% 28/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	30.8% 20/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
General disorders PYREXIA	33.8% 22/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	29.2% 19/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
General disorders CHILLS	18.5% 12/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	18.5% 12/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
General disorders PAIN	18.5% 12/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	18.5% 12/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
General disorders ASTHENIA	16.9% 11/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	10.8% 7/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
General disorders CHEST PAIN	10.8% 7/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	9.2% 6/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
General disorders MUCOSAL INFLAMMATION	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	10.8% 7/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
General disorders OEDEMA	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	9.2% 6/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
General disorders INJECTION SITE PAIN	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
General disorders INJECTION SITE IRRITATION	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Blood and lymphatic system disorders ANAEMIA	60.0% 39/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	47.7% 31/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Blood and lymphatic system disorders NEUTROPENIA	44.6% 29/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	49.2% 32/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Blood and lymphatic system disorders THROMBOCYTOPENIA	24.6% 16/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	29.2% 19/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Blood and lymphatic system disorders LEUKOPENIA	12.3% 8/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	13.8% 9/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Metabolism and nutrition disorders ANOREXIA	32.3% 21/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	27.7% 18/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Metabolism and nutrition disorders HYPOKALAEMIA	30.8% 20/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	18.5% 12/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Metabolism and nutrition disorders DECREASED APPETITE	23.1% 15/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	10.8% 7/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Metabolism and nutrition disorders DEHYDRATION	21.5% 14/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	9.2% 6/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Metabolism and nutrition disorders HYPERGLYCAEMIA	20.0% 13/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	10.8% 7/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Metabolism and nutrition disorders HYPOCALCAEMIA	23.1% 15/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Metabolism and nutrition disorders HYPOALBUMINAEMIA	23.1% 15/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Metabolism and nutrition disorders HYPOMAGNESAEMIA	23.1% 15/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Metabolism and nutrition disorders HYPONATRAEMIA	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Investigations ALANINE AMINOTRANSFERASE INCREASED	33.8% 22/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	33.8% 22/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	35.4% 23/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	32.3% 21/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Investigations HAEMOGLOBIN DECREASED	15.4% 10/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	16.9% 11/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Investigations BLOOD LACTATE DEHYDROGENASE INCREASED	10.8% 7/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	12.3% 8/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Investigations BLOOD CREATININE INCREASED	10.8% 7/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Investigations BLOOD ALKALINE PHOSPHATASE INCREASED	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	9.2% 6/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Investigations EJECTION FRACTION DECREASED	10.8% 7/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Investigations NEUTROPHIL COUNT DECREASED	10.8% 7/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Investigations BLOOD ALBUMIN DECREASED	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Investigations WHITE BLOOD CELL COUNT DECREASED	9.2% 6/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Investigations PLATELET COUNT DECREASED	10.8% 7/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Investigations WEIGHT DECREASED	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Investigations BLOOD GLUCOSE INCREASED	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Investigations BLOOD URINE PRESENT	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Musculoskeletal and connective tissue disorders BACK PAIN	27.7% 18/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	41.5% 27/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	29.2% 19/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	18.5% 12/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Musculoskeletal and connective tissue disorders ARTHRALGIA	23.1% 15/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	13.8% 9/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Musculoskeletal and connective tissue disorders MYALGIA	15.4% 10/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	12.3% 8/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Musculoskeletal and connective tissue disorders FLANK PAIN	9.2% 6/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	9.2% 6/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Musculoskeletal and connective tissue disorders NECK PAIN	9.2% 6/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Musculoskeletal and connective tissue disorders BONE PAIN	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	3.1% 2/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Musculoskeletal and connective tissue disorders MUSCULAR WEAKNESS	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL CHEST PAIN	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	30.8% 20/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	29.2% 19/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Respiratory, thoracic and mediastinal disorders COUGH	29.2% 19/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	29.2% 19/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Respiratory, thoracic and mediastinal disorders EPISTAXIS	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	23.1% 15/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Respiratory, thoracic and mediastinal disorders RHINORRHOEA	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	15.4% 10/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Respiratory, thoracic and mediastinal disorders PHARYNGOLARYNGEAL PAIN	9.2% 6/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	12.3% 8/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Nervous system disorders HEADACHE	29.2% 19/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	36.9% 24/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Nervous system disorders DYSGEUSIA	13.8% 9/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	10.8% 7/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Nervous system disorders DIZZINESS	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Nervous system disorders NEUROPATHY	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Nervous system disorders NEUROPATHY PERIPHERAL	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Nervous system disorders HYPOAESTHESIA	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	3.1% 2/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Skin and subcutaneous tissue disorders RASH	26.2% 17/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	40.0% 26/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Skin and subcutaneous tissue disorders PRURITUS	13.8% 9/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	18.5% 12/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Skin and subcutaneous tissue disorders HYPERHIDROSIS	9.2% 6/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Skin and subcutaneous tissue disorders ERYTHEMA	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Skin and subcutaneous tissue disorders ALOPECIA	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Skin and subcutaneous tissue disorders DRY SKIN	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Skin and subcutaneous tissue disorders ACNE	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Psychiatric disorders INSOMNIA	24.6% 16/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	16.9% 11/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Psychiatric disorders ANXIETY	18.5% 12/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	10.8% 7/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Psychiatric disorders DEPRESSION	15.4% 10/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	10.8% 7/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Infections and infestations URINARY TRACT INFECTION	24.6% 16/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	18.5% 12/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Infections and infestations CELLULITIS	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Infections and infestations SINUSITIS	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Renal and urinary disorders DYSURIA	20.0% 13/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	9.2% 6/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Renal and urinary disorders MICTURITION URGENCY	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Renal and urinary disorders POLLAKIURIA	9.2% 6/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Renal and urinary disorders HYDRONEPHROSIS	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	3.1% 2/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Renal and urinary disorders HAEMATURIA	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Renal and urinary disorders NOCTURIA	0.00% 0/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Vascular disorders FLUSHING	10.8% 7/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Vascular disorders HOT FLUSH	9.2% 6/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	3.1% 2/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Vascular disorders HYPOTENSION	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Vascular disorders DEEP VEIN THROMBOSIS	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Cardiac disorders LEFT VENTRICULAR DYSFUNCTION	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Cardiac disorders TACHYCARDIA	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Eye disorders VISION BLURRED	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Reproductive system and breast disorders VULVOVAGINAL DRYNESS	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	7.7% 5/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Injury, poisoning and procedural complications CONTUSION	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	4.6% 3/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.
Immune system disorders HYPERSENSITIVITY	1.5% 1/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.	6.2% 4/65 • All adverse events were collected from the beginning of study treatment until 30 days after discontinuation of study treatment. Safety population: All participants who received any amount of study treatment.

Additional Information

Medical Communications

Genentech, Inc.

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