Trial Outcomes & Findings for A Study of Trastuzumab-MCC-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer Who Have Previously Received a Trastuzumab-Containing Regimen (NCT NCT00932373)

Last Updated: 2015-08-26

Results Overview

The time frame for AEs is study treatment initiation until 30 days after last administration of study treatment or at the time of initiation of another anti-cancer therapy, which ever occurs first. The time frame for SAEs is study treatment initiation until 90 days after last administration of study treatment or at the time of initiation of another anti-cancer therapy, which ever occurs first.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

54 participants

Primary outcome timeframe

Study treatment initiation until 30 or 90 days after last administration of study treatment

Results posted on

2015-08-26

Participant Flow

Approximately four centers in the United States were to participate in the study to enroll approximately 50-60 patients. Between 25 April 2006 and 20 May 2008, 54 patients were enrolled and 52 were treated.

Two patients enrolled but discontinued the study prior to receiving study treatment drug, thus 52 patients received at least one dose and are included in the baseline and safety analysis data.

Participant milestones

Participant milestones
Measure	Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 0.3 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 0.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 3.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 4.8 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Weekly Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 1.6 mg/kg Weekly Trastuzumab-MCC-DM1 1.6 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.0 mg/kg Weekly Trastuzumab-MCC-DM1 2.0 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.4 mg/kg Weekly Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.9 mg/kg Weekly Trastuzumab-MCC-DM1 2.9 mg/kg administered intravenously (IV) once a week
Overall Study STARTED	3	1	1	1	15	3	3	3	3	16	3
Overall Study COMPLETED	0	0	0	1	1	0	2	0	1	3	0
Overall Study NOT COMPLETED	3	1	1	0	14	3	1	3	2	13	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 0.3 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 0.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 3.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 4.8 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Weekly Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 1.6 mg/kg Weekly Trastuzumab-MCC-DM1 1.6 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.0 mg/kg Weekly Trastuzumab-MCC-DM1 2.0 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.4 mg/kg Weekly Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.9 mg/kg Weekly Trastuzumab-MCC-DM1 2.9 mg/kg administered intravenously (IV) once a week
Overall Study Progressive disease	3	1	0	10	1	0	2	1	9	2
Overall Study Adverse Event	0	0	0	2	1	0	1	0	2	1
Overall Study Physician Decision	0	0	1	2	0	0	0	0	1	0
Overall Study Dose limiting toxicity	0	0	0	0	1	0	0	0	0	0
Overall Study Withdrawal by Subject	0	0	0	0	0	0	0	1	0	0
Overall Study Clinical progression	0	0	0	0	0	1	0	0	0	0
Overall Study Lack of Efficacy	0	0	0	0	0	0	0	0	1	0

Baseline Characteristics

A Study of Trastuzumab-MCC-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer Who Have Previously Received a Trastuzumab-Containing Regimen

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks n=3 Participants Trastuzumab-MCC-DM1 0.3 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 0.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks n=15 Participants Trastuzumab-MCC-DM1 3.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks n=3 Participants Trastuzumab-MCC-DM1 4.8 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 1.6 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 1.6 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.0 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 2.0 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.4 mg/kg Weekly n=16 Participants Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.9 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 2.9 mg/kg administered intravenously (IV) once a week	Total n=52 Participants Total of all reporting groups
Age, Continuous	60.7 Years STANDARD_DEVIATION 10.1 • n=99 Participants	47.0 Years STANDARD_DEVIATION 0 • n=107 Participants	61.0 Years STANDARD_DEVIATION 0 • n=206 Participants	58.0 Years STANDARD_DEVIATION 0 • n=7 Participants	52.1 Years STANDARD_DEVIATION 10.3 • n=31 Participants	48.0 Years STANDARD_DEVIATION 6.0 • n=30 Participants	55.3 Years STANDARD_DEVIATION 10.0 • n=3 Participants	53.0 Years STANDARD_DEVIATION 6.1 • n=6 Participants	55.3 Years STANDARD_DEVIATION 3.2 • n=114 Participants	50.9 Years STANDARD_DEVIATION 14.0	58.3 Years STANDARD_DEVIATION 11.0 • n=19 Participants	52.9 Years STANDARD_DEVIATION 10.7 • n=4 Participants
Sex: Female, Male Female	3 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants	15 Participants n=31 Participants	3 Participants n=30 Participants	3 Participants n=3 Participants	3 Participants n=6 Participants	3 Participants n=114 Participants	16 Participants	3 Participants n=19 Participants	52 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	0 Participants n=114 Participants	0 Participants	0 Participants n=19 Participants	0 Participants n=4 Participants
Region of Enrollment United States	3 participants n=99 Participants	1 participants n=107 Participants	1 participants n=206 Participants	1 participants n=7 Participants	15 participants n=31 Participants	3 participants n=30 Participants	3 participants n=3 Participants	3 participants n=6 Participants	3 participants n=114 Participants	16 participants	3 participants n=19 Participants	52 participants n=4 Participants

PRIMARY outcome

Timeframe: Study treatment initiation until 30 or 90 days after last administration of study treatment

Population: Safety-evaluable population: All participants who received at least 1 dose of trastuzumab-MCC-DM1

Outcome measures

Outcome measures
Measure	Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks n=3 Participants Trastuzumab-MCC-DM1 0.3 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 0.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks n=15 Participants Trastuzumab-MCC-DM1 3.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks n=3 Participants Trastuzumab-MCC-DM1 4.8 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 1.6 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 1.6 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.0 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 2.0 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.4 mg/kg Weekly n=16 Participants Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.9 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 2.9 mg/kg administered intravenously (IV) once a week
Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment AEs related to treatment	66.7 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants	93.3 percentage of participants	100 percentage of participants	100 percentage of participants	66.7 percentage of participants	100 percentage of participants	87.5 percentage of participants	100 percentage of participants
Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment At least 1 AE	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants
Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment AEs with Grade >=3	33.3 percentage of participants	100 percentage of participants	0 percentage of participants	0 percentage of participants	46.7 percentage of participants	100 percentage of participants	33.3 percentage of participants	66.7 percentage of participants	66.7 percentage of participants	81.3 percentage of participants	33.3 percentage of participants
Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment At least 1 SAE	33.3 percentage of participants	100 percentage of participants	0 percentage of participants	0 percentage of participants	20 percentage of participants	66.7 percentage of participants	33.3 percentage of participants	33.3 percentage of participants	33.3 percentage of participants	50 percentage of participants	0 percentage of participants

PRIMARY outcome

Timeframe: A minimum of 21 days after first dose of trastuzumab-MCC-DM1

Population: Safety Population included all treated patients

DLT is defined as one of the following as per investigator related to study drug: * Grade ≥ 3 non-hematologic, non-hepatic major organ toxicity * Grade ≥ 3 cardiac toxicity, including cardiac troponin I elevation or any new segmental wall abnormality as determined by non-invasive cardiac imaging * Grade ≥ 4 thrombocytopenia * Grade ≥ 4 neutropenia (absolute neutrophil count \< 500/μ L) lasting \> 4 days or accompanied by fever * Grade ≥ 4 anemia * Grade ≥ 3 serum bilirubin, hepatic transaminase (alanine aminotransferase or aspartate aminotransferase), or alkaline phosphatase For patients with Grade 2 hepatic transaminase or alkaline phosphatase levels at baseline as a result of liver metastases or bone metastases, a hepatic transaminase or alkaline phosphatase level ≥ 10 times the upper limit of normal will be considered a DLT. * Weekly cohorts only: Toxicity preventing retreatment on Cycle 1, Day 8 or toxicity preventing re-treatment on Cycle 1, Days 15 and Day 22

Outcome measures

Outcome measures
Measure	Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks n=3 Participants Trastuzumab-MCC-DM1 0.3 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 0.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks n=15 Participants Trastuzumab-MCC-DM1 3.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks n=3 Participants Trastuzumab-MCC-DM1 4.8 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 1.6 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 1.6 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.0 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 2.0 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.4 mg/kg Weekly n=16 Participants Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.9 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 2.9 mg/kg administered intravenously (IV) once a week
Number of Patients With Dose Limiting Toxicities (DLTs)	0 participants	0 participants	0 participants	0 participants	0 participants	2 participants	0 participants	0 participants	0 participants	1 participants	2 participants

PRIMARY outcome

Timeframe: A minimum of 21 days after first dose of trastuzumab-MCC-DM1

Population: Safety evaluable population: All participants who received at least 1 dose of trastuzumab-MCC-DM1

The highest dose level resulting in a DLT in ≤ 1 of 6 patients was declared the MTD.

Outcome measures

Outcome measures
Measure	Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks n=24 Participants Trastuzumab-MCC-DM1 0.3 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks n=28 Participants Trastuzumab-MCC-DM1 0.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 3.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 4.8 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Weekly Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 1.6 mg/kg Weekly Trastuzumab-MCC-DM1 1.6 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.0 mg/kg Weekly Trastuzumab-MCC-DM1 2.0 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.4 mg/kg Weekly Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.9 mg/kg Weekly Trastuzumab-MCC-DM1 2.9 mg/kg administered intravenously (IV) once a week
Maximum Tolerated Dose (MTD)	3.6 mg/kg	2.4 mg/kg	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 3-Week and Weekly Cohorts: Cycle 1 Day 1 Pre-dose 30 minutes and 4 hours after the end of infusion; Cycle 1 Day 2, 3, 4, 8 (Pre-dose 30 minutes after the end of infusion) 11, 15 (Pre-dose 30 minutes after the end of infusion) and 18

Population: Pharmacokinetic-evaluable patients were defined as patients who received at least one dose of T-DM1 with at least one post-dose concentration data point.

Outcome measures

Outcome measures
Measure	Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks n=3 Participants Trastuzumab-MCC-DM1 0.3 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 0.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks n=15 Participants Trastuzumab-MCC-DM1 3.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks n=3 Participants Trastuzumab-MCC-DM1 4.8 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 1.6 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 1.6 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.0 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 2.0 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.4 mg/kg Weekly n=16 Participants Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.9 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 2.9 mg/kg administered intravenously (IV) once a week
Pharmacokinetic (PK) Parameters After the First Dose: Maximum Observed Plasma Concentration Cmax for T-DM1 Concentrations	9.63 μg/mL Standard Deviation 1.73	13.3 μg/mL Standard Deviation 0	20.3 μg/mL Standard Deviation 0	76.3 μg/mL Standard Deviation 0	76.2 μg/mL Standard Deviation 19.1	130 μg/mL Standard Deviation 7.77	29.6 μg/mL Standard Deviation 5.66	34.3 μg/mL Standard Deviation 4.81	48.0 μg/mL Standard Deviation 9.56	54.8 μg/mL Standard Deviation 12.6	78.1 μg/mL Standard Deviation 33.9

PRIMARY outcome

Population: Pharmacokinetic-evaluable patients were defined as patients who received at least one dose of T-DM1 with at least one post-dose concentration data point.

Outcome measures

Outcome measures
Measure	Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks n=3 Participants Trastuzumab-MCC-DM1 0.3 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 0.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks n=15 Participants Trastuzumab-MCC-DM1 3.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks n=3 Participants Trastuzumab-MCC-DM1 4.8 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 1.6 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 1.6 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.0 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 2.0 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.4 mg/kg Weekly n=16 Participants Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.9 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 2.9 mg/kg administered intravenously (IV) once a week
PK Parameters After the First Dose: Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-∞] for T-DM1 Concentrations	14.5 day • μg/mL Standard Deviation 3.39	24.5 day • μg/mL Standard Deviation 0	42.9 day • μg/mL Standard Deviation 0	330 day • μg/mL Standard Deviation 0	300 day • μg/mL Standard Deviation 65.8	673 day • μg/mL Standard Deviation 12.2	76.2 day • μg/mL Standard Deviation 10.4	130 day • μg/mL Standard Deviation 39.7	175 day • μg/mL Standard Deviation 41.0	199 day • μg/mL Standard Deviation 54.5	212 day • μg/mL Standard Deviation 39.0

PRIMARY outcome

Population: Pharmacokinetic-evaluable patients were defined as patients who received at least one dose of T-DM1 with at least one post-dose concentration data point.

Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.

Outcome measures

Outcome measures
Measure	Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks n=3 Participants Trastuzumab-MCC-DM1 0.3 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 0.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks n=15 Participants Trastuzumab-MCC-DM1 3.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks n=3 Participants Trastuzumab-MCC-DM1 4.8 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 1.6 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 1.6 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.0 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 2.0 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.4 mg/kg Weekly n=16 Participants Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.9 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 2.9 mg/kg administered intravenously (IV) once a week
PK Parameters After the First Dose: Terminal Half-life (t½) for T-DM1 Concentrations	1.3 day Standard Deviation 0.2	1.3 day Standard Deviation 0	1.3 day Standard Deviation 0	2.2 day Standard Deviation 0	3.1 day Standard Deviation 0.7	4.1 day Standard Deviation 0.7	2.3 day Standard Deviation 0.6	3.4 day Standard Deviation 0.8	3.1 day Standard Deviation 0.3	3.3 day Standard Deviation 1.1	2.9 day Standard Deviation 0.5

SECONDARY outcome

Timeframe: Baseline to the end of the study (up to 3 years 2 months)

Population: Efficacy population: All enrolled participants who received treatment.

The occurrence of an objective response was determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST). An objective response was defined as a complete response or a partial response as determined on 2 consecutive occasions ≥ 4 weeks apart. 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

Outcome measures
Measure	Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks n=3 Participants Trastuzumab-MCC-DM1 0.3 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 0.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks n=15 Participants Trastuzumab-MCC-DM1 3.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks n=3 Participants Trastuzumab-MCC-DM1 4.8 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 1.6 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 1.6 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.0 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 2.0 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.4 mg/kg Weekly n=16 Participants Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.9 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 2.9 mg/kg administered intravenously (IV) once a week
Percentage of Participants With an Objective Response	0 percentage of participants	0 percentage of participants	0 percentage of participants	100 percentage of participants	26.7 percentage of participants	0 percentage of participants	100 percentage of participants	66.7 percentage of participants	66.7 percentage of participants	37.5 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline to the end of the study (up to 3 years 2 months)

Population: Efficacy population: All enrolled participants who received treatment.

Duration of objective response was defined as the time from the initial response to disease progression or death from any cause within 30 days of the last dose of trastuzumab emtansine.

Outcome measures

Outcome measures
Measure	Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 0.3 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks n=4 Participants Trastuzumab-MCC-DM1 0.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks n=3 Participants Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks n=2 Participants Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks n=2 Participants Trastuzumab-MCC-DM1 3.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks n=6 Participants Trastuzumab-MCC-DM1 4.8 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Weekly Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 1.6 mg/kg Weekly Trastuzumab-MCC-DM1 1.6 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.0 mg/kg Weekly Trastuzumab-MCC-DM1 2.0 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.4 mg/kg Weekly Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.9 mg/kg Weekly Trastuzumab-MCC-DM1 2.9 mg/kg administered intravenously (IV) once a week
Duration of Objective Response	NA Months Not estimable as the median and/or confidence interval limits were not reached.	10.5 Months Interval 4.2 to 10.5	NA Months Not estimable as the median and/or confidence interval limits were not reached.	2.9 Months Not estimable as the median and/or confidence interval limits were not reached.	NA Months Not estimable as the median and/or confidence interval limits were not reached.	5.6 Months Interval 4.5 to Not estimable as the median and/or confidence interval limits were not reached.	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to the end of the study (up to 3 years 2 months)

Population: Efficacy population: All enrolled participants who received treatment.

Progression-free survival was defined as the time from first dose of trastuzumab emtansine to documented disease progression or death from any cause within 30 days of the last dose of trastuzumab emtansine, whichever occurred earlier. Progressive disease 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 of target lesions recorded since treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Outcome measures

Outcome measures
Measure	Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks n=3 Participants Trastuzumab-MCC-DM1 0.3 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 0.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks n=1 Participants Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks n=15 Participants Trastuzumab-MCC-DM1 3.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks n=3 Participants Trastuzumab-MCC-DM1 4.8 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 1.6 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 1.6 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.0 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 2.0 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.4 mg/kg Weekly n=16 Participants Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.9 mg/kg Weekly n=3 Participants Trastuzumab-MCC-DM1 2.9 mg/kg administered intravenously (IV) once a week
Progression-free Survival	2.7 Months Interval 1.3 to 4.2	1.7 Months Not Estimable	NA Months Not Estimable	NA Months Not Estimable	10.4 Months Interval 3.4 to 17.1	NA Months Interval 0.7 to Not Estimable	NA Months Interval 20.8 to Not Estimable	4.5 Months Interval 1.6 to Not Estimable	NA Months Interval 7.2 to Not Estimable	5.7 Months Interval 1.3 to 10.9	2.0 Months Interval 1.3 to 2.8

SECONDARY outcome

Timeframe: Baseline to the end of the study (up to 3 years 2 months)

After the start of trastuzumab emtansine treatment, serum samples were collected every 3 weeks prior to trastuzumab emtansine dosing for detection of anti-therapeutic antibodies using a validated assay. A bridging antibody electrochemiluminescence assay (ECLA) was used to detect antibodies to trastuzumab emtansine. The assay utilized trastuzumab emtansine conjugated to biotin and a ruthenium label to form a complex with anti-trastuzumab emtansine antibodies. The antibody complex was captured by streptavidin-coated paramagnetic beads.

Outcome measures

Outcome measures
Measure	Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks n=24 Participants Trastuzumab-MCC-DM1 0.3 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks n=28 Participants Trastuzumab-MCC-DM1 0.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 3.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 4.8 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM1 1.2 mg/kg Weekly Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 1.6 mg/kg Weekly Trastuzumab-MCC-DM1 1.6 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.0 mg/kg Weekly Trastuzumab-MCC-DM1 2.0 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.4 mg/kg Weekly Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM1 2.9 mg/kg Weekly Trastuzumab-MCC-DM1 2.9 mg/kg administered intravenously (IV) once a week
Percentage of Participants With Anti-therapeutic Antibodies to Trastuzumab Emtansine Any Visit after Dosing	4.3 percentage of participants	0.0 percentage of participants	—	—	—	—	—	—	—	—	—
Percentage of Participants With Anti-therapeutic Antibodies to Trastuzumab Emtansine Pre-dose (Cycle 1, Day 1)	0.0 percentage of participants	3.7 percentage of participants	—	—	—	—	—	—	—	—	—

Deaths: 0 deaths

Trastuzumab-MCC-DM 2.9 mg/kg Weekly

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Trastuzumab-MCC-DM 0.3 mg/kg Every 3 Weeks n=3 participants at risk Trastuzumab-MCC-DM 0.3 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM 0.6 mg/kg Every 3 Weeks n=1 participants at risk Trastuzumab-MCC-DM 0.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM 1.2 mg/kg Every 3 Weeks n=1 participants at risk Trastuzumab-MCC-DM 1.2 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM 2.4 mg/kg Every 3 Weeks n=1 participants at risk Trastuzumab-MCC-DM 2.4 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM 3.6 mg/kg Every 3 Weeks n=15 participants at risk Trastuzumab-MCC-DM 3.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM 4.8 mg/kg Every 3 Weeks n=3 participants at risk Trastuzumab-MCC-DM 4.8 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM 1.2 mg/kg Weekly n=3 participants at risk Trastuzumab-MCC-DM 1.2 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM 1.6 mg/kg Weekly n=3 participants at risk Trastuzumab-MCC-DM 1.6 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM 2.0 mg/kg Weekly n=3 participants at risk Trastuzumab-MCC-DM 2.0 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM 2.4 mg/kg Weekly n=16 participants at risk Trastuzumab-MCC-DM 2.4 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM 2.9 mg/kg Weekly n=3 participants at risk 2.9 mg/kg administered intravenously (IV) once a week
General disorders Pain	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	6.2% 1/16 • Number of events 1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Infections and infestations Cellulitis	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Number of events 1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	6.2% 1/16 • Number of events 1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Infections and infestations Influenza	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	6.2% 1/16 • Number of events 1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Infections and infestations Osteomyelitis	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	6.2% 1/16 • Number of events 1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Infections and infestations Pneumonia	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Number of events 1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	12.5% 2/16 • Number of events 2 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Injury, poisoning and procedural complications Humerus Fracture	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Number of events 1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Nervous system disorders Brain Oedema	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Number of events 1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Nervous system disorders Cerebral Haemorrhage	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Number of events 1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Nervous system disorders Convulsion	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Number of events 1 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Number of events 1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Nervous system disorders Dysarthria	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Number of events 1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Nervous system disorders Hepatic Encephalopathy	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	6.2% 1/16 • Number of events 1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Psychiatric disorders Confusional State	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Number of events 1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	33.3% 1/3 • Number of events 1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	6.2% 1/16 • Number of events 1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Number of events 1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Number of events 1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	6.2% 1/16 • Number of events 1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Respiratory, thoracic and mediastinal disorders Pulmonary Hypertension	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Number of events 1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)

Other adverse events

Other adverse events
Measure	Trastuzumab-MCC-DM 0.3 mg/kg Every 3 Weeks n=3 participants at risk Trastuzumab-MCC-DM 0.3 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM 0.6 mg/kg Every 3 Weeks n=1 participants at risk Trastuzumab-MCC-DM 0.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM 1.2 mg/kg Every 3 Weeks n=1 participants at risk Trastuzumab-MCC-DM 1.2 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM 2.4 mg/kg Every 3 Weeks n=1 participants at risk Trastuzumab-MCC-DM 2.4 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM 3.6 mg/kg Every 3 Weeks n=15 participants at risk Trastuzumab-MCC-DM 3.6 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM 4.8 mg/kg Every 3 Weeks n=3 participants at risk Trastuzumab-MCC-DM 4.8 mg/kg administered intravenously (IV) once every 3 weeks	Trastuzumab-MCC-DM 1.2 mg/kg Weekly n=3 participants at risk Trastuzumab-MCC-DM 1.2 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM 1.6 mg/kg Weekly n=3 participants at risk Trastuzumab-MCC-DM 1.6 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM 2.0 mg/kg Weekly n=3 participants at risk Trastuzumab-MCC-DM 2.0 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM 2.4 mg/kg Weekly n=16 participants at risk Trastuzumab-MCC-DM 2.4 mg/kg administered intravenously (IV) once a week	Trastuzumab-MCC-DM 2.9 mg/kg Weekly n=3 participants at risk 2.9 mg/kg administered intravenously (IV) once a week
Investigations WEIGHT DECREASED	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	6.2% 1/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Gastrointestinal disorders ORAL PAIN	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Investigations ALANINE AMINOTRANSFERASE	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Baseline to the end of the study (up to 3 years 2 months)	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	12.5% 2/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Injury, poisoning and procedural complications JOINT SPRAIN	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Gastrointestinal disorders DYSPEPSIA	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	12.5% 2/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) TUMOUR PAIN	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Infections and infestations URINARY TRACT INFECTION	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 5/15 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	6.2% 1/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Renal and urinary disorders NEPHROLITHIASIS	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Respiratory, thoracic and mediastinal disorders DYSPNOEA	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	26.7% 4/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	56.2% 9/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Infections and infestations NASOPHARYNGITIS	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	20.0% 3/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	12.5% 2/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Musculoskeletal and connective tissue disorders MYALGIA	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	13.3% 2/15 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Gastrointestinal disorders VOMITING	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	20.0% 3/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	37.5% 6/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
General disorders MUCOSAL INFLAMMATION	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Musculoskeletal and connective tissue disorders PATHOLOGICAL FRACTURE	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Blood and lymphatic system disorders NEUTROPENIA	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	6.2% 1/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Investigations LIPASE INCREASED	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	6.2% 1/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Metabolism and nutrition disorders HYPOKALAEMIA	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	26.7% 4/15 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	12.5% 2/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Skin and subcutaneous tissue disorders PERIORBITAL OEDEMA	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Cardiac disorders TACHYCARDIA	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Metabolism and nutrition disorders HYPOCALCAEMIA	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
General disorders OEDEMA PERIPHERAL	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Skin and subcutaneous tissue disorders HYPERHIDROSIS	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Gastrointestinal disorders DIARRHOEA	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	13.3% 2/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 3/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)	37.5% 6/16 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)
Gastrointestinal disorders NAUSEA	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	40.0% 6/15 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 3/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	43.8% 7/16 • Baseline to the end of the study (up to 3 years 2 months)	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)
Psychiatric disorders DISORIENTATION	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL CHEST PAIN	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	26.7% 4/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Skin and subcutaneous tissue disorders DRY SKIN	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	12.5% 2/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Nervous system disorders SYNCOPE	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) TUMOUR NECROSIS	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Gastrointestinal disorders DRY MOUTH	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	20.0% 3/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	43.8% 7/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Blood and lymphatic system disorders IRON DEFICIENCY ANAEMIA	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	6.2% 1/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Musculoskeletal and connective tissue disorders ARTHRALGIA	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	20.0% 3/15 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)	6.2% 1/16 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)
Eye disorders LACRIMATION INCREASED	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	12.5% 2/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Eye disorders DRY EYE	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	18.8% 3/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Gastrointestinal disorders RETCHING	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Injury, poisoning and procedural complications SUBDURAL HAEMATOMA	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Investigations BLOOD ALKALINE PHOSPHATASE INCREASED	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	6.2% 1/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Metabolism and nutrition disorders DECREASED APPETITE	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	18.8% 3/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Metabolism and nutrition disorders FLUID RETENTION	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
General disorders CHEST PAIN	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	20.0% 3/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	6.2% 1/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
General disorders FATIGUE	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	60.0% 9/15 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 3/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 3/3 • Baseline to the end of the study (up to 3 years 2 months)	62.5% 10/16 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)
Vascular disorders FLUSHING	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Infections and infestations TOOTH ABSCESS	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
General disorders CHILLS	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)
Respiratory, thoracic and mediastinal disorders HAEMOPTYSIS	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	6.2% 1/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	6.2% 1/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
General disorders INFLUENZA LIKE ILLNESS	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Gastrointestinal disorders STOMATITIS	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	6.2% 1/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Gastrointestinal disorders CONSTIPATION	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	20.0% 3/15 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)	25.0% 4/16 • Baseline to the end of the study (up to 3 years 2 months)	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	13.3% 2/15 • Baseline to the end of the study (up to 3 years 2 months)	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)	50.0% 8/16 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)
Investigations LIVER FUNCTION TEST ABNORMAL	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	26.7% 4/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	12.5% 2/16 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)
General disorders PYREXIA	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	20.0% 3/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)	12.5% 2/16 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)
Psychiatric disorders INSOMNIA	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)	18.8% 3/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Reproductive system and breast disorders MENSTRUAL DISORDER	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Nervous system disorders DYSGEUSIA	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	18.8% 3/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Blood and lymphatic system disorders ANAEMIA	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	40.0% 6/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	37.5% 6/16 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)
Infections and infestations RESPIRATORY TRACT INFECTION	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Metabolism and nutrition disorders HYPONATRAEMIA	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Nervous system disorders DIZZINESS	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	13.3% 2/15 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	12.5% 2/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Psychiatric disorders MENTAL STATUS CHANGES	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Skin and subcutaneous tissue disorders RASH MACULAR	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Metabolism and nutrition disorders ANOREXIA	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	13.3% 2/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	25.0% 4/16 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)
Immune system disorders DRUG HYPERSENSITIVITY	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Eye disorders EYE PAIN	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	6.2% 1/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Musculoskeletal and connective tissue disorders NECK PAIN	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	6.2% 1/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Blood and lymphatic system disorders THROMBOCYTOPENIA	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	60.0% 9/15 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 3/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)	37.5% 6/16 • Baseline to the end of the study (up to 3 years 2 months)	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)
Musculoskeletal and connective tissue disorders FLANK PAIN	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	13.3% 2/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Nervous system disorders NEUROPATHY PERIPHERAL	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	18.8% 3/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Respiratory, thoracic and mediastinal disorders PRODUCTIVE COUGH	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
General disorders ASTHENIA	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Eye disorders CONJUNCTIVITIS	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	12.5% 2/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Respiratory, thoracic and mediastinal disorders RALES	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Respiratory, thoracic and mediastinal disorders EPISTAXIS	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	20.0% 3/15 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)	31.2% 5/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	6.7% 1/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	6.2% 1/16 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)
Respiratory, thoracic and mediastinal disorders COUGH	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	26.7% 4/15 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)	31.2% 5/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Skin and subcutaneous tissue disorders COLD SWEAT	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
General disorders FACIAL PAIN	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
General disorders FACE OEDEMA	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Eye disorders VISION BLURRED	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/15 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	6.2% 1/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)
Nervous system disorders HEADACHE	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/1 • Baseline to the end of the study (up to 3 years 2 months)	100.0% 1/1 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 5/15 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	66.7% 2/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	33.3% 1/3 • Baseline to the end of the study (up to 3 years 2 months)	43.8% 7/16 • Baseline to the end of the study (up to 3 years 2 months)	0.00% 0/3 • Baseline to the end of the study (up to 3 years 2 months)

Additional Information

Medical Communications

Genentech, Inc.

Phone: 800 821-8590

Email: [email protected]

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