Trial Outcomes & Findings for Bioavailability and Pharmacokinetics of Vedolizumab in Healthy Participants Following Single Subcutaneous Administration (NCT NCT02163421)

Last Updated: 2017-02-01

Results Overview

Bioavailability is defined as the rate and extent to which the active moiety of the e.g. subcutaneous administered drug reaches the systemic circulation. Population mean estimate for bioavailability was based on population pharmacokinetic (PK) analysis to find one measure. The exposure data were pooled across visits and subjects to identify population PK parameter estimates and covariate effects. The outcome measure data was planned to be analyzed using a model collating all arms measures to report pooled data across arms, as per planned analysis. Bioavailability was estimated using population pharmacokinetic (popPK) analysis.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

48 participants

Primary outcome timeframe

Day 1: predose and on multiple time points (up to Day 127)

Results posted on

2017-02-01

Participant Flow

Participants took part in the study at 1 investigative site in the United Kingdom from 09 June 2014 to 16 January 2015.

Healthy participants of age group 18 years to 60 years were enrolled in 1 of the 4 treatment groups: Vedolizumab intravenous 300 milligram (mg); Vedolizumab subcutaneous 54 mg; Vedolizumab SC 108 mg and Vedolizumab SC 160 mg.

Participant milestones

Participant milestones
Measure	Vedolizumab Intravenous 300 mg Vedolizumab 300 mg, 30-minutes infusion, intravenously once only on Day 1 in a treatment period of 168 days.	Vedolizumab Subcutaneous 54 mg Vedolizumab 54 mg, injection, subcutaneously, once only on Day 1 in a treatment period of 168 days.	Vedolizumab Subcutaneous 108 mg Vedolizumab 108 mg, injection, subcutaneously, once only on Day 1 in a treatment period of 168 days.	Vedolizumab Subcutaneous 160 mg Vedolizumab 160 mg, injection, subcutaneously, once only on Day 1 in a treatment period of 168 days.
Overall Study STARTED	12	12	12	12
Overall Study COMPLETED	12	12	12	12
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Bioavailability and Pharmacokinetics of Vedolizumab in Healthy Participants Following Single Subcutaneous Administration

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vedolizumab Intravenous 300 mg n=12 Participants Vedolizumab 300 mg, 30-minutes infusion, intravenously once only on Day 1 in a treatment period of 168 days.	Vedolizumab Subcutaneous 54 mg n=12 Participants Vedolizumab 54 mg, injection, subcutaneously, once only on Day 1 in a treatment period of 168 days.	Vedolizumab Subcutaneous 108 mg n=12 Participants Vedolizumab 108 mg, injection, subcutaneously, once only on Day 1 in a treatment period of 168 days.	Vedolizumab Subcutaneous 160 mg n=12 Participants Vedolizumab 160 mg, injection, subcutaneously, once only on Day 1 in a treatment period of 168 days.	Total n=48 Participants Total of all reporting groups
Age, Continuous	33.9 years STANDARD_DEVIATION 12.30 • n=5 Participants	41.0 years STANDARD_DEVIATION 13.06 • n=7 Participants	31.1 years STANDARD_DEVIATION 9.59 • n=5 Participants	35.2 years STANDARD_DEVIATION 12.89 • n=4 Participants	35.3 years STANDARD_DEVIATION 12.21 • n=21 Participants
Gender Female	4 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants	19 Participants n=21 Participants
Gender Male	8 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants	7 Participants n=4 Participants	29 Participants n=21 Participants
Race/Ethnicity, Customized Asian	6 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	6 participants n=4 Participants	24 participants n=21 Participants
Race/Ethnicity, Customized White	5 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	6 participants n=4 Participants	23 participants n=21 Participants
Race/Ethnicity, Customized Multiracial	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Weight	65.8 kilogram (kg) STANDARD_DEVIATION 13.84 • n=5 Participants	68.0 kilogram (kg) STANDARD_DEVIATION 12.96 • n=7 Participants	67.6 kilogram (kg) STANDARD_DEVIATION 13.42 • n=5 Participants	64.3 kilogram (kg) STANDARD_DEVIATION 14.58 • n=4 Participants	66.4 kilogram (kg) STANDARD_DEVIATION 13.35 • n=21 Participants
Body Mass Index (BMI)	21.8 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.90 • n=5 Participants	23.0 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.98 • n=7 Participants	22.8 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.44 • n=5 Participants	22.0 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.41 • n=4 Participants	22.4 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.90 • n=21 Participants
Smoking Classification Had Never Smoked	8 participants n=5 Participants	9 participants n=7 Participants	10 participants n=5 Participants	6 participants n=4 Participants	33 participants n=21 Participants
Smoking Classification Current Smoker	3 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	5 participants n=4 Participants	11 participants n=21 Participants
Smoking Classification Ex-Smoker	1 participants n=5 Participants	2 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	4 participants n=21 Participants
Alcohol Classification Had Never Drunk	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants	2 participants n=21 Participants
Alcohol Classification Current Drinker	11 participants n=5 Participants	9 participants n=7 Participants	9 participants n=5 Participants	9 participants n=4 Participants	38 participants n=21 Participants
Alcohol Classification Ex-Drinker	1 participants n=5 Participants	3 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants	8 participants n=21 Participants
Female Reproductive Status Postmenopausal Female	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Female Reproductive Status Female of Childbearing Potential	4 participants n=5 Participants	4 participants n=7 Participants	5 participants n=5 Participants	5 participants n=4 Participants	18 participants n=21 Participants
Female Reproductive Status Not Applicable (Participant was Male)	8 participants n=5 Participants	7 participants n=7 Participants	7 participants n=5 Participants	7 participants n=4 Participants	29 participants n=21 Participants

PRIMARY outcome

Timeframe: Day 1: predose and on multiple time points (up to Day 127)

Population: The pharmacokinetic analysis set included all randomized participants who received study treatment and who had at least 1 measurable pharmacokinetic concentration.

Outcome measures

Outcome measures
Measure	Vedolizumab Subcutaneous n=36 Participants Vedolizumab 54 mg or 108 mg or 160 mg, injection, subcutaneously, once only on Day 1 in a treatment period of 168 days.
Population Mean Estimate for Bioavailability Following Subcutaneous (SC) Administration	0.751 percentage of drug Interval 0.689 to 0.819

Adverse Events

Vedolizumab Intravenous 300 mg

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Vedolizumab Subcutaneous 54 mg

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Vedolizumab Subcutaneous 108 mg

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Vedolizumab Subcutaneous 160 mg

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER

Other adverse events
Measure	Vedolizumab Intravenous 300 mg n=12 participants at risk Vedolizumab 300 mg, 30-minutes infusion, intravenously once only on Day 1 in a treatment period of 168 days.	Vedolizumab Subcutaneous 54 mg n=12 participants at risk Vedolizumab 54 mg, injection, subcutaneously, once only on Day 1 in a treatment period of 168 days.	Vedolizumab Subcutaneous 108 mg n=12 participants at risk Vedolizumab 108 mg, injection, subcutaneously, once only on Day 1 in a treatment period of 168 days.	Vedolizumab Subcutaneous 160 mg n=12 participants at risk Vedolizumab 160 mg, injection, subcutaneously, once only on Day 1 in a treatment period of 168 days.
Nervous system disorders Headache	25.0% 3/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	25.0% 3/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	25.0% 3/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Presyncope	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 2/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Dizziness	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	25.0% 3/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 2/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Constipation	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Nausea	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Toothache	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Injection site reaction	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Pyrexia	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Vessel puncture site swelling	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Immune system disorders Seasonal allergy	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Cellulitis	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Gastroenteritis	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Hordeolum	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Nasopharyngitis	16.7% 2/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 2/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 2/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	25.0% 3/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Rhinitis	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Upper respiratory tract infection	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Decreased appetite	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Muscle fatigue	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Plantar fasciitis	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Depressed level of consciousness	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Memory impairment	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Migraine	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Paraesthesia	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Somnolence	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Urine odour abnormal	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Reproductive system and breast disorders Dysmenorrhoea	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Cough	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Sneezing	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 1/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/12 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 168 days after the last dose of study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.