Trial Outcomes & Findings for A Dose-range Finding Study of MAA868 in Patients With Atrial Fibrillation (NCT NCT04213807)

Last Updated: 2022-01-11

Results Overview

Number of participants achieving more than or equal to 50%, 80%, and 90% inhibition of factor XI (less than 50%, 20%, or 10% free factor XI) at trough after the third dose on Day 91 at different dose levels of MAA868

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

28 participants

Primary outcome timeframe

Day 91

Results posted on

2022-01-11

Participant Flow

No subjects were enrolled in the optional Cohort 3.

28 participants were screened. 5 participants did not meet inclusion/exclusion criteria; 5 eligible participants failed randomization.

Participant milestones

Participant milestones
Measure	Placebo Subcutaneous injection of placebo on Day 1, Day 31, and Day 61	MAA868 120 mg Subcutaneous injection of 120 mg MAA868 on Day 1, Day 31, and Day 61	MAA868 180 mg Subcutaneous injection of 180 mg MAA868 on Day 1, Day 31, and Day 61
Overall Study STARTED	5	6	7
Overall Study COMPLETED	5	6	6
Overall Study NOT COMPLETED	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Subcutaneous injection of placebo on Day 1, Day 31, and Day 61	MAA868 120 mg Subcutaneous injection of 120 mg MAA868 on Day 1, Day 31, and Day 61	MAA868 180 mg Subcutaneous injection of 180 mg MAA868 on Day 1, Day 31, and Day 61
Overall Study Physician Decision	0	0	1

Baseline Characteristics

A Dose-range Finding Study of MAA868 in Patients With Atrial Fibrillation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=5 Participants Subcutaneous injection of placebo on Day 1, Day 31, and Day 61	MAA868 120 mg n=6 Participants Subcutaneous injection of 120 mg MAA868 on Day 1, Day 31, and Day 61	MAA868 180 mg n=7 Participants Subcutaneous injection of 180 mg MAA868 on Day 1, Day 31, and Day 61	Total n=18 Participants Total of all reporting groups
Age, Continuous	52.2 years STANDARD_DEVIATION 18.79 • n=5 Participants	53.8 years STANDARD_DEVIATION 9.24 • n=7 Participants	58.1 years STANDARD_DEVIATION 8.34 • n=5 Participants	55.1 years STANDARD_DEVIATION 11.81 • n=4 Participants
Age, Customized 18 to 20	1 years n=5 Participants	0 years n=7 Participants	0 years n=5 Participants	1 years n=4 Participants
Age, Customized 21 to 30	0 years n=5 Participants	0 years n=7 Participants	0 years n=5 Participants	0 years n=4 Participants
Age, Customized 31 to 40	0 years n=5 Participants	1 years n=7 Participants	0 years n=5 Participants	1 years n=4 Participants
Age, Customized 41 to 50	0 years n=5 Participants	0 years n=7 Participants	1 years n=5 Participants	1 years n=4 Participants
Age, Customized 51 to 60	2 years n=5 Participants	4 years n=7 Participants	4 years n=5 Participants	10 years n=4 Participants
Age, Customized 61 to 70	2 years n=5 Participants	1 years n=7 Participants	2 years n=5 Participants	5 years n=4 Participants
Age, Customized 71 to 80	0 years n=5 Participants	0 years n=7 Participants	0 years n=5 Participants	0 years n=4 Participants
Age, Customized 81 to 85	0 years n=5 Participants	0 years n=7 Participants	0 years n=5 Participants	0 years n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	13 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	18 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	16 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Height	182.01 centimeters STANDARD_DEVIATION 5.573 • n=5 Participants	174.60 centimeters STANDARD_DEVIATION 11.311 • n=7 Participants	175.74 centimeters STANDARD_DEVIATION 8.337 • n=5 Participants	177.10 centimeters STANDARD_DEVIATION 8.918 • n=4 Participants
Weight	99.352 kg STANDARD_DEVIATION 13.1715 • n=5 Participants	91.667 kg STANDARD_DEVIATION 7.1102 • n=7 Participants	94.933 kg STANDARD_DEVIATION 23.2745 • n=5 Participants	95.072 kg STANDARD_DEVIATION 16.0115 • n=4 Participants
Body mass index	30.022 kg/m^2 STANDARD_DEVIATION 4.1647 • n=5 Participants	30.392 kg/m^2 STANDARD_DEVIATION 4.7558 • n=7 Participants	30.887 kg/m^2 STANDARD_DEVIATION 8.6754 • n=5 Participants	30.482 kg/m^2 STANDARD_DEVIATION 6.1179 • n=4 Participants

PRIMARY outcome

Timeframe: Day 91

Population: Pharmacokinetic/Pharmacodynamic Set

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Subcutaneous injection of placebo on Day 1, Day 31, and Day 61	MAA868 120 mg n=6 Participants Subcutaneous injection of 120 mg MAA868 on Day 1, Day 31, and Day 61	MAA868 180 mg n=7 Participants Subcutaneous injection of 180 mg MAA868 on Day 1, Day 31, and Day 61
Number of Participants That Achieved More Than or Equal to 50%, 80%, and 90% Factor XI Inhibition at Trough After the Third Dose (Day 91) at Different Dose Levels of MAA868 More than or equal to 90% inhibition of factor XI	0 Participants	0 Participants	0 Participants
Number of Participants That Achieved More Than or Equal to 50%, 80%, and 90% Factor XI Inhibition at Trough After the Third Dose (Day 91) at Different Dose Levels of MAA868 More than or equal to 50% inhibition of factor XI	0 Participants	2 Participants	4 Participants
Number of Participants That Achieved More Than or Equal to 50%, 80%, and 90% Factor XI Inhibition at Trough After the Third Dose (Day 91) at Different Dose Levels of MAA868 More than or equal to 80% inhibition of factor XI	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 31 and Day 61

Population: Pharmacokinetic/Pharmacodynamic Set

Number of participants achieving more than or equal to 50%, 80%, and 90% inhibition of factor XI (less than 50%, 20%, or 10% free factor XI) at trough on Day 31 (after first dose) and Day 61 (after second dose) at different dose levels of MAA868

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Subcutaneous injection of placebo on Day 1, Day 31, and Day 61	MAA868 120 mg n=6 Participants Subcutaneous injection of 120 mg MAA868 on Day 1, Day 31, and Day 61	MAA868 180 mg n=7 Participants Subcutaneous injection of 180 mg MAA868 on Day 1, Day 31, and Day 61
Number of Participants Achieving More Than or Equal to 50%, 80%, and 90% Factor XI Inhibition at Trough After First (Day 31) and Second Doses (Day 61) at Different Dose Levels of MAA868 More than or equal to 50% factor XI inhibition : Day 31	0 Participants	1 Participants	5 Participants
Number of Participants Achieving More Than or Equal to 50%, 80%, and 90% Factor XI Inhibition at Trough After First (Day 31) and Second Doses (Day 61) at Different Dose Levels of MAA868 More than or equal to 80% factor XI inhibition : Day 61	0 Participants	0 Participants	1 Participants
Number of Participants Achieving More Than or Equal to 50%, 80%, and 90% Factor XI Inhibition at Trough After First (Day 31) and Second Doses (Day 61) at Different Dose Levels of MAA868 More than or equal to 90% factor XI inhibition : Day 61	0 Participants	0 Participants	0 Participants
Number of Participants Achieving More Than or Equal to 50%, 80%, and 90% Factor XI Inhibition at Trough After First (Day 31) and Second Doses (Day 61) at Different Dose Levels of MAA868 More than or equal to 50% factor XI inhibition : Day 61	0 Participants	2 Participants	5 Participants
Number of Participants Achieving More Than or Equal to 50%, 80%, and 90% Factor XI Inhibition at Trough After First (Day 31) and Second Doses (Day 61) at Different Dose Levels of MAA868 More than or equal to 80% factor XI inhibition : Day 31	0 Participants	1 Participants	3 Participants
Number of Participants Achieving More Than or Equal to 50%, 80%, and 90% Factor XI Inhibition at Trough After First (Day 31) and Second Doses (Day 61) at Different Dose Levels of MAA868 More than or equal to 90% factor XI inhibition : Day 31	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 through end of study, up to 170 days

Population: Safety Set

Overall number of participants who experienced adverse events following multiple subcutaneous administration of MAA868 compared to placebo in participants with atrial fibrillation or atrial flutter

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Subcutaneous injection of placebo on Day 1, Day 31, and Day 61	MAA868 120 mg n=6 Participants Subcutaneous injection of 120 mg MAA868 on Day 1, Day 31, and Day 61	MAA868 180 mg n=7 Participants Subcutaneous injection of 180 mg MAA868 on Day 1, Day 31, and Day 61
Overall Number of Participants Who Experienced Adverse Events, Including Serious Adverse Events, During the Treatment Period and Through End of Study	4 Participants	5 Participants	3 Participants

SECONDARY outcome

Timeframe: Day 1 through end of study, up to 170 days

Population: Safety Set

Occurrence of confirmed major bleeding events, clinically relevant non-major bleeding events and total bleeding events during the treatment period

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Subcutaneous injection of placebo on Day 1, Day 31, and Day 61	MAA868 120 mg n=6 Participants Subcutaneous injection of 120 mg MAA868 on Day 1, Day 31, and Day 61	MAA868 180 mg n=7 Participants Subcutaneous injection of 180 mg MAA868 on Day 1, Day 31, and Day 61
Incidence of Major Bleeding Events, Clinically Relevant Non-major Bleeding Events and Total Bleeding With MAA868 Relative to Placebo Nuisance (not clinically relevant) bleeding events	2 incidence of events	1 incidence of events	1 incidence of events
Incidence of Major Bleeding Events, Clinically Relevant Non-major Bleeding Events and Total Bleeding With MAA868 Relative to Placebo Major bleeding events	0 incidence of events	0 incidence of events	0 incidence of events
Incidence of Major Bleeding Events, Clinically Relevant Non-major Bleeding Events and Total Bleeding With MAA868 Relative to Placebo Clinically relevant non-major bleeding events	0 incidence of events	0 incidence of events	0 incidence of events
Incidence of Major Bleeding Events, Clinically Relevant Non-major Bleeding Events and Total Bleeding With MAA868 Relative to Placebo No bleeding events	0 incidence of events	1 incidence of events	0 incidence of events

SECONDARY outcome

Timeframe: Days 1, 31, 61, 71, 91, 121 and 170

Population: Safety Set

Number of participants with anti-drug (MAA868) antibodies for all participants who received MAA868 120 mg or MAA868 180 mg. "Non-evaluable observation" refers to participants who had no sample collected (due to no visit or remote visit) or for whom the sample was not frozen.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Subcutaneous injection of placebo on Day 1, Day 31, and Day 61	MAA868 120 mg n=7 Participants Subcutaneous injection of 120 mg MAA868 on Day 1, Day 31, and Day 61	MAA868 180 mg Subcutaneous injection of 180 mg MAA868 on Day 1, Day 31, and Day 61
Immunogenicity of MAA868 Baseline · Non-evaluable observation	0 Participants	0 Participants	—
Immunogenicity of MAA868 Day 1 · Negative	6 Participants	7 Participants	—
Immunogenicity of MAA868 Day 1 · Non-evaluable observation	0 Participants	0 Participants	—
Immunogenicity of MAA868 Day 31 · Negative	6 Participants	7 Participants	—
Immunogenicity of MAA868 Day 61 · Non-evaluable observation	3 Participants	1 Participants	—
Immunogenicity of MAA868 Day 71 · Negative	4 Participants	6 Participants	—
Immunogenicity of MAA868 Day 91 · Non-evaluable observation	1 Participants	2 Participants	—
Immunogenicity of MAA868 Day 121 · Negative	5 Participants	5 Participants	—
Immunogenicity of MAA868 Day 121 · Positive	0 Participants	0 Participants	—
Immunogenicity of MAA868 Day 121 · Non-evaluable observation	1 Participants	2 Participants	—
Immunogenicity of MAA868 Day 170 · Negative	6 Participants	7 Participants	—
Immunogenicity of MAA868 Day 170 · Positive	0 Participants	0 Participants	—
Immunogenicity of MAA868 Day 31 · Positive	0 Participants	0 Participants	—
Immunogenicity of MAA868 Baseline · Negative	6 Participants	7 Participants	—
Immunogenicity of MAA868 Baseline · Positive	0 Participants	0 Participants	—
Immunogenicity of MAA868 Day 1 · Positive	0 Participants	0 Participants	—
Immunogenicity of MAA868 Day 31 · Non-evaluable observation	0 Participants	0 Participants	—
Immunogenicity of MAA868 Day 61 · Negative	3 Participants	6 Participants	—
Immunogenicity of MAA868 Day 61 · Positive	0 Participants	0 Participants	—
Immunogenicity of MAA868 Day 71 · Positive	0 Participants	0 Participants	—
Immunogenicity of MAA868 Day 71 · Non-evaluable observation	2 Participants	1 Participants	—
Immunogenicity of MAA868 Day 91 · Negative	5 Participants	5 Participants	—
Immunogenicity of MAA868 Day 91 · Positive	0 Participants	0 Participants	—
Immunogenicity of MAA868 Day 170 · Non-evaluable observation	0 Participants	0 Participants	—

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

MAA868 120 mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

MAA868 180 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Debra Freedholm

Anthos Therapeutics

Phone: 609-439-8246

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigator agrees that no submission for publication or public disclosure by the Investigator will be made until after publication of the results of the Multicenter Trial, except as set forth in the clinical trial agreement. If, however, there is no multicenter publication within eighteen (18) months after completion or termination of the Study, Investigator may publish or publicly present the Study Data in accordance with the clinical trial agreement.
Publication restrictions are in place

Restriction type: OTHER

Other adverse events
Measure	Placebo n=5 participants at risk Subcutaneous injection of placebo on Day 1, Day 31, and Day 61	MAA868 120 mg n=6 participants at risk Subcutaneous injection of 120 mg MAA868 on Day 1, Day 31, and Day 61	MAA868 180 mg n=7 participants at risk Subcutaneous injection of 180 mg MAA868 on Day 1, Day 31, and Day 61
Musculoskeletal and connective tissue disorders Back pain	20.0% 1/5 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/6 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	14.3% 1/7 • Number of events 2 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/5 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	16.7% 1/6 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/7 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Musculoskeletal and connective tissue disorders Muscle spasms	20.0% 1/5 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/6 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/7 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/5 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/6 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	14.3% 1/7 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/5 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	16.7% 1/6 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/7 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Gastrointestinal disorders Diarrhoea	20.0% 1/5 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	16.7% 1/6 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/7 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Gastrointestinal disorders Abdominal pain	0.00% 0/5 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	16.7% 1/6 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/7 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Gastrointestinal disorders Dental caries	0.00% 0/5 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	16.7% 1/6 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/7 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Infections and infestations Gastroenteritis	0.00% 0/5 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	16.7% 1/6 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/7 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Infections and infestations Herpes simplex	0.00% 0/5 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	16.7% 1/6 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/7 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Infections and infestations Otitis media	0.00% 0/5 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	16.7% 1/6 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/7 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Infections and infestations Sinusitis	0.00% 0/5 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	16.7% 1/6 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/7 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Investigations Blood pressure increased	20.0% 1/5 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/6 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/7 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Investigations Coagulation test abnormal	0.00% 0/5 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/6 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	14.3% 1/7 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Investigations Eosinophil count increased	20.0% 1/5 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/6 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/7 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Renal and urinary disorders Dysuria	0.00% 0/5 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	16.7% 1/6 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/7 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Renal and urinary disorders Haematuria	0.00% 0/5 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	16.7% 1/6 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/7 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Renal and urinary disorders Nephrolithiasis	0.00% 0/5 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	16.7% 1/6 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/7 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Renal and urinary disorders Renal impairment	20.0% 1/5 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/6 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/7 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/5 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/6 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	14.3% 1/7 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Cardiac disorders Atrial flutter	0.00% 0/5 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	16.7% 1/6 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/7 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Injury, poisoning and procedural complications Contusion	20.0% 1/5 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/6 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/7 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Nervous system disorders Syncope	0.00% 0/5 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	16.7% 1/6 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/7 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Reproductive system and breast disorders Prostatitis	0.00% 0/5 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/6 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	14.3% 1/7 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/5 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	16.7% 1/6 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/7 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/5 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	16.7% 1/6 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/7 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Vascular disorders Haematoma	20.0% 1/5 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/6 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/7 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.
Gastrointestinal disorders Gingival bleeding	0.00% 0/5 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	0.00% 0/6 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.	14.3% 1/7 • Number of events 1 • Adverse event information was collected at every study visit from providing written informed consent for participation in the study (on Days -28 to -3) until Day 170 (the end of study visit). The occurrence of adverse events was to be sought by non-directive questioning of the participants at each visit by the site staff during the study (e.g., "How are you feeling today?" or "How have you been feeling since your last visit") to elicit adverse event information from the participant. Adverse events might have been detected when they were volunteered by the participants during or between visits or through physical examination finding, laboratory test finding, or other assessments.