Trial Outcomes & Findings for A Dose-Finding Study of Subcutaneous Herceptin (Trastuzumab) in Healthy Male Volunteers and Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Females (NCT NCT00800436)

NCT ID: NCT00800436

Last Updated: 2016-12-16

Results Overview

AUCinf represents the area under the concentration-time curve of trastuzumab in serum over the time interval from 0 extrapolated to infinity. Values for AUCinf of trastuzumab were derived by non-compartmental analysis across all pharmacokinetic (PK) collections and expressed in days by micrograms per milliliter (days•μg/mL).

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 66 participants
• Primary outcome timeframe: Predose (0 hours) and postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)
• Results posted on: 2016-12-16

Participant Flow

Four participants were counted twice as they were treated in both Cohort 2 and Cohort A.

Participant milestones

Measure	Part 1: Cohort 1 Healthy male participants received Herceptin 6 milligrams per kilogram (mg/kg) intravenously (IV) on Day 1.	Part 1: Cohort 2 Female participants with human epidermal growth factor receptor 2 (HER2)-positive breast cancer received Herceptin 6 mg/kg IV on Day 1.	Part 1: Cohort 3 Healthy male participants received Herceptin 6 mg/kg subcutaneously (SC) on Day 1.	Part 1: Cohort 4 Healthy male participants received Herceptin 10 mg/kg SC on Day 1.	Part 1: Cohort 5 Healthy male participants received Herceptin 8 mg/kg SC on Day 1.	Part 2: Cohort A Female participants with HER2-positive breast cancer received Herceptin 8 mg/kg SC on Day 1.	Part 2: Cohort B Female participants with HER2-positive breast cancer received Herceptin 12 mg/kg SC on Day 1.
Overall Study STARTED	6	6	6	6	6	20	20
Overall Study COMPLETED	6	6	5	5	6	20	20
Overall Study NOT COMPLETED	0	0	1	1	0	0	0

Reasons for withdrawal

Measure	Part 1: Cohort 1 Healthy male participants received Herceptin 6 milligrams per kilogram (mg/kg) intravenously (IV) on Day 1.	Part 1: Cohort 2 Female participants with human epidermal growth factor receptor 2 (HER2)-positive breast cancer received Herceptin 6 mg/kg IV on Day 1.	Part 1: Cohort 3 Healthy male participants received Herceptin 6 mg/kg subcutaneously (SC) on Day 1.	Part 1: Cohort 4 Healthy male participants received Herceptin 10 mg/kg SC on Day 1.	Part 1: Cohort 5 Healthy male participants received Herceptin 8 mg/kg SC on Day 1.	Part 2: Cohort A Female participants with HER2-positive breast cancer received Herceptin 8 mg/kg SC on Day 1.	Part 2: Cohort B Female participants with HER2-positive breast cancer received Herceptin 12 mg/kg SC on Day 1.
Overall Study Withdrawal by Subject	0	0	1	1	0	0	0

Baseline Characteristics

A Dose-Finding Study of Subcutaneous Herceptin (Trastuzumab) in Healthy Male Volunteers and Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Females

Baseline characteristics by cohort

Measure	Part 1: Cohort 1 n=6 Participants Healthy male participants received Herceptin 6 mg/kg IV on Day 1.	Part 1: Cohort 2 n=6 Participants Female participants with HER2-positive breast cancer received Herceptin 6 mg/kg IV on Day 1.	Part 1: Cohort 3 n=6 Participants Healthy male participants received Herceptin 6 mg/kg SC on Day 1.	Part 1: Cohort 4 n=6 Participants Healthy male participants received Herceptin 10 mg/kg SC on Day 1.	Part 1: Cohort 5 n=6 Participants Healthy male participants received Herceptin 8 mg/kg SC on Day 1.	Part 2: Cohort A n=20 Participants Female participants with HER2-positive breast cancer received Herceptin 8 mg/kg SC on Day 1.	Part 2: Cohort B n=20 Participants Female participants with HER2-positive breast cancer received Herceptin 12 mg/kg SC on Day 1.	Total n=70 Participants Total of all reporting groups
Age, Continuous	22.7 years STANDARD_DEVIATION 2.58 • n=93 Participants	46.2 years STANDARD_DEVIATION 5.19 • n=4 Participants	25.7 years STANDARD_DEVIATION 9.29 • n=27 Participants	23.0 years STANDARD_DEVIATION 6.16 • n=483 Participants	22.0 years STANDARD_DEVIATION 4.34 • n=36 Participants	50.7 years STANDARD_DEVIATION 7.21 • n=10 Participants	51.6 years STANDARD_DEVIATION 9.04 • n=115 Participants	41.2 years STANDARD_DEVIATION 14.85 • n=40 Participants
Gender Female	0 Participants n=93 Participants	6 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	20 Participants n=10 Participants	20 Participants n=115 Participants	46 Participants n=40 Participants
Gender Male	6 Participants n=93 Participants	0 Participants n=4 Participants	6 Participants n=27 Participants	6 Participants n=483 Participants	6 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	24 Participants n=40 Participants

PRIMARY outcome

Timeframe: Predose (0 hours) and postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)

Population: PK Population: All enrolled participants who adhered to the protocol (per protocol basis).

AUCinf represents the area under the concentration-time curve of trastuzumab in serum over the time interval from 0 extrapolated to infinity. Values for AUCinf of trastuzumab were derived by non-compartmental analysis across all pharmacokinetic (PK) collections and expressed in days by micrograms per milliliter (days•μg/mL).

Outcome measures

Measure	Part 1: Cohort 1 n=6 Participants Healthy male participants received Herceptin 6 mg/kg IV on Day 1.	Part 1: Cohort 2 n=6 Participants Female participants with HER2-positive breast cancer received Herceptin 6 mg/kg IV on Day 1.	Part 1: Cohort 3 n=6 Participants Healthy male participants received Herceptin 6 mg/kg SC on Day 1.	Part 1: Cohort 4 n=6 Participants Healthy male participants received Herceptin 10 mg/kg SC on Day 1.	Part 1: Cohort 5 n=6 Participants Healthy male participants received Herceptin 8 mg/kg SC on Day 1.	Part 2: Cohort A n=20 Participants Female participants with HER2-positive breast cancer received Herceptin 8 mg/kg SC on Day 1.	Part 2: Cohort B n=20 Participants Female participants with HER2-positive breast cancer received Herceptin 12 mg/kg SC on Day 1.
Area Under the Concentration-Time Curve Extrapolated to Infinity (AUCinf) of Trastuzumab	1610 days•μg/mL Standard Deviation 303	1800 days•μg/mL Standard Deviation 250	1350 days•μg/mL Standard Deviation 320	2500 days•μg/mL Standard Deviation 515	1960 days•μg/mL Standard Deviation 244	2090 days•μg/mL Standard Deviation 638	3550 days•μg/mL Standard Deviation 982

SECONDARY outcome

Timeframe: Day 22

Population: PK Population

CDay22 of trastuzumab was derived from the single PK collection on Day 22 and expressed in micrograms per milliliter (μg/mL).

Outcome measures

Measure	Part 1: Cohort 1 n=6 Participants Healthy male participants received Herceptin 6 mg/kg IV on Day 1.	Part 1: Cohort 2 n=6 Participants Female participants with HER2-positive breast cancer received Herceptin 6 mg/kg IV on Day 1.	Part 1: Cohort 3 n=6 Participants Healthy male participants received Herceptin 6 mg/kg SC on Day 1.	Part 1: Cohort 4 n=6 Participants Healthy male participants received Herceptin 10 mg/kg SC on Day 1.	Part 1: Cohort 5 n=6 Participants Healthy male participants received Herceptin 8 mg/kg SC on Day 1.	Part 2: Cohort A n=20 Participants Female participants with HER2-positive breast cancer received Herceptin 8 mg/kg SC on Day 1.	Part 2: Cohort B n=20 Participants Female participants with HER2-positive breast cancer received Herceptin 12 mg/kg SC on Day 1.
Trough Serum Concentration on Day 22 (CDay22) of Trastuzumab	25.6 μg/mL Standard Deviation 12.1	27.5 μg/mL Standard Deviation 7.5	31.6 μg/mL Standard Deviation 12.0	51.4 μg/mL Standard Deviation 15.8	39.4 μg/mL Standard Deviation 5.5	37.8 μg/mL Standard Deviation 10.4	60.8 μg/mL Standard Deviation 22.0

SECONDARY outcome

Timeframe: Postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)

Population: PK Population

Cmax of trastuzumab was derived across all post-dose PK collections and expressed in μg/mL.

Outcome measures

Measure	Part 1: Cohort 1 n=6 Participants Healthy male participants received Herceptin 6 mg/kg IV on Day 1.	Part 1: Cohort 2 n=6 Participants Female participants with HER2-positive breast cancer received Herceptin 6 mg/kg IV on Day 1.	Part 1: Cohort 3 n=6 Participants Healthy male participants received Herceptin 6 mg/kg SC on Day 1.	Part 1: Cohort 4 n=6 Participants Healthy male participants received Herceptin 10 mg/kg SC on Day 1.	Part 1: Cohort 5 n=6 Participants Healthy male participants received Herceptin 8 mg/kg SC on Day 1.	Part 2: Cohort A n=20 Participants Female participants with HER2-positive breast cancer received Herceptin 8 mg/kg SC on Day 1.	Part 2: Cohort B n=20 Participants Female participants with HER2-positive breast cancer received Herceptin 12 mg/kg SC on Day 1.
Maximum Observed Serum Concentration of Trastuzumab (Cmax)	150 μg/mL Standard Deviation 14.4	185 μg/mL Standard Deviation 42.9	66.8 μg/mL Standard Deviation 11.4	102 μg/mL Standard Deviation 17.2	82.0 μg/mL Standard Deviation 11.3	88.4 μg/mL Standard Deviation 33.3	151 μg/mL Standard Deviation 58.6

SECONDARY outcome

Timeframe: Postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)

Population: PK Population

Tmax of trastuzumab was based on the Cmax derived across all post-dose PK collections and expressed in hours.

Outcome measures

Measure	Part 1: Cohort 1 n=6 Participants Healthy male participants received Herceptin 6 mg/kg IV on Day 1.	Part 1: Cohort 2 n=6 Participants Female participants with HER2-positive breast cancer received Herceptin 6 mg/kg IV on Day 1.	Part 1: Cohort 3 n=6 Participants Healthy male participants received Herceptin 6 mg/kg SC on Day 1.	Part 1: Cohort 4 n=6 Participants Healthy male participants received Herceptin 10 mg/kg SC on Day 1.	Part 1: Cohort 5 n=6 Participants Healthy male participants received Herceptin 8 mg/kg SC on Day 1.	Part 2: Cohort A n=20 Participants Female participants with HER2-positive breast cancer received Herceptin 8 mg/kg SC on Day 1.	Part 2: Cohort B n=20 Participants Female participants with HER2-positive breast cancer received Herceptin 12 mg/kg SC on Day 1.
Time to Maximum Serum Concentration (Tmax) of Trastuzumab	1.65 hours Interval 1.6 to 24.0	3.00 hours Interval 1.55 to 24.0	156.00 hours Interval 95.95 to 216.1	132.12 hours Interval 96.0 to 216.0	96.00 hours Interval 96.0 to 215.98	97.13 hours Interval 47.93 to 216.6	96.05 hours Interval 24.53 to 241.4

SECONDARY outcome

Timeframe: Postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)

Population: PK Population

T1/2 of trastuzumab was measured as the time required for trastuzumab concentration to decrease by one-half. T1/2 was derived across all PK collections and expressed in hours.

Outcome measures

Measure	Part 1: Cohort 1 n=6 Participants Healthy male participants received Herceptin 6 mg/kg IV on Day 1.	Part 1: Cohort 2 n=6 Participants Female participants with HER2-positive breast cancer received Herceptin 6 mg/kg IV on Day 1.	Part 1: Cohort 3 n=6 Participants Healthy male participants received Herceptin 6 mg/kg SC on Day 1.	Part 1: Cohort 4 n=6 Participants Healthy male participants received Herceptin 10 mg/kg SC on Day 1.	Part 1: Cohort 5 n=6 Participants Healthy male participants received Herceptin 8 mg/kg SC on Day 1.	Part 2: Cohort A n=20 Participants Female participants with HER2-positive breast cancer received Herceptin 8 mg/kg SC on Day 1.	Part 2: Cohort B n=20 Participants Female participants with HER2-positive breast cancer received Herceptin 12 mg/kg SC on Day 1.
Terminal Elimination Half-Life (T1/2) of Trastuzumab	254 hours Standard Deviation 32.2	244 hours Standard Deviation 69.2	227 hours Standard Deviation 55.9	240 hours Standard Deviation 34.4	236 hours Standard Deviation 43.9	241 hours Standard Deviation 48.1	270 hours Standard Deviation 80.1

Adverse Events

Part 1: Cohort 1

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Part 1: Cohort 2

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Part 1: Cohort 3

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Part 1: Cohort 4

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Part 1: Cohort 5

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Part 2: Cohort A

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Part 2: Cohort B

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Part 1: Cohort 1 n=6 participants at risk Healthy male participants received Herceptin 6 mg/kg IV on Day 1.	Part 1: Cohort 2 n=6 participants at risk Female participants with HER2-positive breast cancer received Herceptin 6 mg/kg IV on Day 1.	Part 1: Cohort 3 n=6 participants at risk Healthy male participants received Herceptin 6 mg/kg SC on Day 1.	Part 1: Cohort 4 n=6 participants at risk Healthy male participants received Herceptin 10 mg/kg SC on Day 1.	Part 1: Cohort 5 n=6 participants at risk Healthy male participants received Herceptin 8 mg/kg SC on Day 1.	Part 2: Cohort A n=20 participants at risk Female participants with HER2-positive breast cancer received Herceptin 8 mg/kg SC on Day 1.	Part 2: Cohort B n=20 participants at risk Female participants with HER2-positive breast cancer received Herceptin 12 mg/kg SC on Day 1.
General disorders Injection site discomfort	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
General disorders Injection site reaction	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
General disorders Vessel puncture site haematoma	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
General disorders Catheter site inflammation	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Nervous system disorders Headache	50.0% 3/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	33.3% 2/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	33.3% 2/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	33.3% 2/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	60.0% 12/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	70.0% 14/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
General disorders Fatigue	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	10.0% 2/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	15.0% 3/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
General disorders Injection site erythema	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	20.0% 4/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	10.0% 2/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
General disorders Chest pain	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	10.0% 2/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	10.0% 2/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
General disorders Injection site discolouration	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	33.3% 2/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	15.0% 3/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
General disorders Influenza like illness	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
General disorders Catheter site haematoma	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
General disorders Injection site pain	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	10.0% 2/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
General disorders Pyrexia	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	10.0% 2/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
General disorders Infusion related reaction	33.3% 2/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
General disorders Injection site swelling	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	10.0% 2/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
General disorders Oedema peripheral	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
General disorders Application site inflammation	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
General disorders Application site reaction	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
General disorders Application site vesicles	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
General disorders Catheter site erythema	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
General disorders Feeling cold	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
General disorders Gravitational oedema	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
General disorders Inflammation	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Nervous system disorders Lethargy	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	20.0% 4/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	10.0% 2/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Nervous system disorders Dizziness	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	10.0% 2/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Nervous system disorders Restless leg syndrome	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Nervous system disorders Convulsion	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Nervous system disorders Hypoaesthesia	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Nervous system disorders Somnolence	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Nervous system disorders Tremor	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Infections and infestations Upper respiratory tract Infection	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	33.3% 2/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	20.0% 4/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	25.0% 5/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Infections and infestations Urinary tract infection	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	10.0% 2/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Infections and infestations Gastroenteritis	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	10.0% 2/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Infections and infestations Influenza	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Infections and infestations Lower respiratory tract infection	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	10.0% 2/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Infections and infestations Oral herpes	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Infections and infestations Viral infection	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	10.0% 2/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Infections and infestations Campylobacter infection	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Infections and infestations Dermatitis infected	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Infections and infestations Herpes simplex	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Infections and infestations Herpes zoster	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Infections and infestations Hordeolum	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Infections and infestations Nasopharyngitis	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Infections and infestations Paronychia	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Infections and infestations Respiratory tract infection	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Infections and infestations Respiratory tract infection viral	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Infections and infestations Sinusitis	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Infections and infestations Tooth abscess	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Infections and infestations Viral upper respiratory tract infection	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Pain in extremity	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	15.0% 3/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	15.0% 3/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	15.0% 3/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Athralgia	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	10.0% 2/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	10.0% 2/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Musculoskeletal pain	33.3% 2/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	10.0% 2/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	10.0% 2/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Joint crepitation	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Gastrointestinal disorders Diarrhoea	33.3% 2/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	30.0% 6/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	10.0% 2/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Gastrointestinal disorders Nausea	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	15.0% 3/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Gastrointestinal disorders Abdominal discomfort	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	10.0% 2/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Gastrointestinal disorders Abdominal pain	33.3% 2/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Gastrointestinal disorders Dry mouth	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Gastrointestinal disorders Abdominal distension	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Gastrointestinal disorders Aphthous stomatitis	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Gastrointestinal disorders Dyspepsia	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Gastrointestinal disorders Faecal incontinence	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Gastrointestinal disorders Flatulence	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Gastrointestinal disorders Toothache	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Gastrointestinal disorders Vomiting	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	10.0% 2/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	10.0% 2/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Dry throat	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Dysponea	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Nasal congestation	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Pharyngeal stenosis	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Postnasal drip	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Sneezing	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Contusion	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Tooth fracture	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Chest injury	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Excoriation	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Incision site pain	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Joint sprain	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Meniscus lesion	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Skin laceration	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Acne	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	33.3% 2/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Erythema	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Rash	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Rash papular	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Eye disorders Eye irritation	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Eye disorders Conjuctival haemorrhage	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Eye disorders Eyelid bleeding	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Eye disorders Scleral hypermia	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Psychiatric disorders Depressed mood	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	10.0% 2/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Psychiatric disorders Initial insomnia	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Psychiatric disorders Panic attack	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Vascular disorders Flushing	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Vascular disorders Hot flush	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Vascular disorders Lymphoedema	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Investigations Breath sounds abnormal	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Investigations Weight decreased	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Investigations Weight increased	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Reproductive system and breast disorders Breast mass	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Reproductive system and breast disorders Nipple pain	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Cardiac disorders Mitral valve incompetence	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	5.0% 1/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Ear and labyrinth disorders Ear pain	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population
Immune system disorders Seasonal allergy	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	16.7% 1/6 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population	0.00% 0/20 • From Baseline up to 5 months post-dose (up to 5 months overall) Analysis Population Description: Safety Population

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

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

Restriction type: OTHER