Trial Outcomes & Findings for A Phase 2 Study to Evaluate the Efficacy and Safety of VIR-2482 for the Prevention of Illness Due to Influenza A (NCT NCT05567783)

Last Updated: 2024-09-19

Results Overview

Protocol-defined ILI with confirmed influenza A defined as RT-PCR confirmed influenza A with at least one respiratory symptom and at least one systemic symptom

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

2977 participants

Primary outcome timeframe

Up to 24 Weeks

Results posted on

2024-09-19

Participant Flow

Participant milestones

Participant milestones
Measure	VIR-2482 (450 mg) VIR-2482 (450 mg): VIR-2482 450 mg given by intramuscular injection	VIR-2482 (1200 mg) VIR-2482 (1200 mg): VIR-2482 1200 mg given by intramuscular injection	Placebo Placebo: Sterile 0.9% (w/v) sodium chloride solution given by intramuscular injection
Overall Study STARTED	989	995	993
Overall Study Received Study Intervention	981	992	983
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	989	995	993

Reasons for withdrawal

Reasons for withdrawal
Measure	VIR-2482 (450 mg) VIR-2482 (450 mg): VIR-2482 450 mg given by intramuscular injection	VIR-2482 (1200 mg) VIR-2482 (1200 mg): VIR-2482 1200 mg given by intramuscular injection	Placebo Placebo: Sterile 0.9% (w/v) sodium chloride solution given by intramuscular injection
Overall Study Death	2	3	0
Overall Study Lost to Follow-up	25	19	17
Overall Study Physician Decision	10	7	9
Overall Study Study Terminated by Sponsor	924	937	941
Overall Study Withdrawal by Subject	23	27	24
Overall Study Incarcerated	1	0	0
Overall Study Participant randomized in error	4	2	2

Baseline Characteristics

A Phase 2 Study to Evaluate the Efficacy and Safety of VIR-2482 for the Prevention of Illness Due to Influenza A

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	VIR-2482 (450 mg) n=981 Participants VIR-2482 (450 mg): VIR-2482 450mg given by intramuscular injection	VIR-2482 (1200 mg) n=992 Participants VIR-2482 (1200 mg): VIR-2482 1200 mg given by intramuscular injection	Placebo n=983 Participants Placebo: Sterile 0.9% (w/v) sodium chloride solution given by intramuscular injection	Total n=2956 Participants Total of all reporting groups
Age, Continuous	39.2 Years STANDARD_DEVIATION 12.52 • n=5 Participants	39.6 Years STANDARD_DEVIATION 11.73 • n=7 Participants	39.7 Years STANDARD_DEVIATION 12.29 • n=5 Participants	39.5 Years STANDARD_DEVIATION 12.18 • n=4 Participants
Sex: Female, Male Female	545 Participants n=5 Participants	523 Participants n=7 Participants	530 Participants n=5 Participants	1598 Participants n=4 Participants
Sex: Female, Male Male	436 Participants n=5 Participants	469 Participants n=7 Participants	453 Participants n=5 Participants	1358 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	371 Participants n=5 Participants	369 Participants n=7 Participants	357 Participants n=5 Participants	1097 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	606 Participants n=5 Participants	622 Participants n=7 Participants	620 Participants n=5 Participants	1848 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants	11 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	7 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants	21 Participants n=4 Participants
Race (NIH/OMB) Asian	26 Participants n=5 Participants	29 Participants n=7 Participants	26 Participants n=5 Participants	81 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	5 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	13 Participants n=4 Participants
Race (NIH/OMB) Black or African American	154 Participants n=5 Participants	176 Participants n=7 Participants	166 Participants n=5 Participants	496 Participants n=4 Participants
Race (NIH/OMB) White	752 Participants n=5 Participants	747 Participants n=7 Participants	758 Participants n=5 Participants	2257 Participants n=4 Participants
Race (NIH/OMB) More than one race	17 Participants n=5 Participants	11 Participants n=7 Participants	6 Participants n=5 Participants	34 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	20 Participants n=5 Participants	18 Participants n=7 Participants	16 Participants n=5 Participants	54 Participants n=4 Participants
Region of Enrollment United States	981 participants n=5 Participants	992 participants n=7 Participants	983 participants n=5 Participants	2956 participants n=4 Participants
Body Mass Index	27.34 kg/m^2 STANDARD_DEVIATION 4.085 • n=5 Participants	27.44 kg/m^2 STANDARD_DEVIATION 4.167 • n=7 Participants	27.4 kg/m^2 STANDARD_DEVIATION 4.071 • n=5 Participants	27.34 kg/m^2 STANDARD_DEVIATION 4.107 • n=4 Participants

PRIMARY outcome

Timeframe: Up to 24 Weeks

Population: Full Analysis Set (all randomized who did not have confirmed influenza infection within 3 months prior to randomization, did not receive an influenza vaccination for the upcoming influenza season, and received any amount of study intervention). Participants were analyzed according to the randomized study intervention.

Protocol-defined ILI with confirmed influenza A defined as RT-PCR confirmed influenza A with at least one respiratory symptom and at least one systemic symptom

Outcome measures

Outcome measures
Measure	VIR-2482 (450 mg) n=981 Participants VIR-2482 (450 mg): VIR-2482 450 mg given by intramuscular injection	VIR-2482 (1200 mg) n=992 Participants VIR-2482 (1200 mg): VIR-2482 1200 mg given by intramuscular injection	Placebo n=983 Participants Placebo: Sterile 0.9% (w/v) sodium chloride solution given by intramuscular injection
Percentage of Participants With Protocol-defined Influenza-like Illness (ILI) With Confirmed Influenza A (by Reverse Transcription Polymerase Chain Reaction [RT-PCR])	2.45 percentage of participants	2.12 percentage of participants	2.54 percentage of participants

PRIMARY outcome

Timeframe: Up to 26 Weeks

Population: Participants who received any amount of study intervention. Participants were analyzed according to study intervention received.

Outcome measures

Outcome measures
Measure	VIR-2482 (450 mg) n=981 Participants VIR-2482 (450 mg): VIR-2482 450 mg given by intramuscular injection	VIR-2482 (1200 mg) n=992 Participants VIR-2482 (1200 mg): VIR-2482 1200 mg given by intramuscular injection	Placebo n=983 Participants Placebo: Sterile 0.9% (w/v) sodium chloride solution given by intramuscular injection
Number of Participants With Adverse Events (AEs)	636 Participants	613 Participants	639 Participants

PRIMARY outcome

Timeframe: Up to 26 Weeks

Population: Participants who received any amount of study intervention. Participants were analyzed according to the study intervention received.

Outcome measures

Outcome measures
Measure	VIR-2482 (450 mg) n=981 Participants VIR-2482 (450 mg): VIR-2482 450 mg given by intramuscular injection	VIR-2482 (1200 mg) n=992 Participants VIR-2482 (1200 mg): VIR-2482 1200 mg given by intramuscular injection	Placebo n=983 Participants Placebo: Sterile 0.9% (w/v) sodium chloride solution given by intramuscular injection
Number of Participants With Serious Adverse Events (SAEs)	10 Participants	13 Participants	9 Participants

PRIMARY outcome

Timeframe: Up to 26 Weeks

AESI is anaphylaxis per MedDRA anaphylaxis algorithmic SMQ

Outcome measures

Outcome measures
Measure	VIR-2482 (450 mg) n=981 Participants VIR-2482 (450 mg): VIR-2482 450 mg given by intramuscular injection	VIR-2482 (1200 mg) n=992 Participants VIR-2482 (1200 mg): VIR-2482 1200 mg given by intramuscular injection	Placebo n=983 Participants Placebo: Sterile 0.9% (w/v) sodium chloride solution given by intramuscular injection
Number of Participants With Adverse Events of Special Interest (AESI)	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 26 Weeks

Population: Participants who received any amount of study intervention and had a post-baseline vital sign measurement. Participants were analyzed according to the study intervention received.

Defined as a graded abnormality in systolic blood pressure, diastolic blood pressure, pulse, respiratory rate, or oral temperature as per the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials at any time on/after receipt of study intervention.

Outcome measures

Outcome measures
Measure	VIR-2482 (450 mg) n=981 Participants VIR-2482 (450 mg): VIR-2482 450 mg given by intramuscular injection	VIR-2482 (1200 mg) n=992 Participants VIR-2482 (1200 mg): VIR-2482 1200 mg given by intramuscular injection	Placebo n=981 Participants Placebo: Sterile 0.9% (w/v) sodium chloride solution given by intramuscular injection
Number of Participants With Vital Sign Abnormalities	678 Participants	662 Participants	648 Participants

PRIMARY outcome

Timeframe: Up to 26 Weeks

Population: Participants who received any amount of study intervention and had a post-baseline clinical laboratory assessment. Participants were analyzed according to the study intervention received.

Defined as graded abnormality in chemistry, hematology, liver function, or urinalysis clinical laboratory values as per the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Trials at any time on/after receipt of study intervention.

Outcome measures

Outcome measures
Measure	VIR-2482 (450 mg) n=978 Participants VIR-2482 (450 mg): VIR-2482 450 mg given by intramuscular injection	VIR-2482 (1200 mg) n=988 Participants VIR-2482 (1200 mg): VIR-2482 1200 mg given by intramuscular injection	Placebo n=976 Participants Placebo: Sterile 0.9% (w/v) sodium chloride solution given by intramuscular injection
Number of Participants With Clinical Laboratory Abnormalities	961 Participants	971 Participants	961 Participants

PRIMARY outcome

Timeframe: Up to Day 7 following study intervention administration

Population: Participants who received any amount of study intervention . Participants were analyzed according to the study intervention received.

Injection site reactions from the study intervention diary card

Outcome measures

Outcome measures
Measure	VIR-2482 (450 mg) n=981 Participants VIR-2482 (450 mg): VIR-2482 450 mg given by intramuscular injection	VIR-2482 (1200 mg) n=992 Participants VIR-2482 (1200 mg): VIR-2482 1200 mg given by intramuscular injection	Placebo n=983 Participants Placebo: Sterile 0.9% (w/v) sodium chloride solution given by intramuscular injection
Number of Participants With Solicited Injection Site Reactions Any injection site reaction	292 Participants	293 Participants	272 Participants
Number of Participants With Solicited Injection Site Reactions Pain	279 Participants	277 Participants	260 Participants
Number of Participants With Solicited Injection Site Reactions Erythema	7 Participants	10 Participants	5 Participants
Number of Participants With Solicited Injection Site Reactions Induration	8 Participants	12 Participants	3 Participants
Number of Participants With Solicited Injection Site Reactions Swelling	10 Participants	13 Participants	2 Participants
Number of Participants With Solicited Injection Site Reactions Bruising	17 Participants	20 Participants	21 Participants

PRIMARY outcome

Timeframe: Up to Day 7 following study intervention administration

Population: Participants who received any amount of study intervention . Participants were analyzed according to the study intervention received.

Systemic reactions from the study intervention diary card

Outcome measures

Outcome measures
Measure	VIR-2482 (450 mg) n=981 Participants VIR-2482 (450 mg): VIR-2482 450 mg given by intramuscular injection	VIR-2482 (1200 mg) n=992 Participants VIR-2482 (1200 mg): VIR-2482 1200 mg given by intramuscular injection	Placebo n=983 Participants Placebo: Sterile 0.9% (w/v) sodium chloride solution given by intramuscular injection
Number of Participants With Solicited Systemic Reactions Any systemic reaction	265 Participants	283 Participants	268 Participants
Number of Participants With Solicited Systemic Reactions Headache	160 Participants	168 Participants	175 Participants
Number of Participants With Solicited Systemic Reactions Myalgia	135 Participants	169 Participants	149 Participants
Number of Participants With Solicited Systemic Reactions Malaise	117 Participants	130 Participants	123 Participants
Number of Participants With Solicited Systemic Reactions Shivering	44 Participants	60 Participants	43 Participants
Number of Participants With Solicited Systemic Reactions Fever	11 Participants	11 Participants	13 Participants

SECONDARY outcome

Timeframe: Up to 24 Weeks

CDC-defined ILI with RT-PCR confirmed influenza A

Outcome measures

Outcome measures
Measure	VIR-2482 (450 mg) n=981 Participants VIR-2482 (450 mg): VIR-2482 450 mg given by intramuscular injection	VIR-2482 (1200 mg) n=992 Participants VIR-2482 (1200 mg): VIR-2482 1200 mg given by intramuscular injection	Placebo n=983 Participants Placebo: Sterile 0.9% (w/v) sodium chloride solution given by intramuscular injection
Percentage of Participants With CDC-defined Influenza-like Illness (ILI) With Confirmed Influenza A (by Reverse Transcription Polymerase Chain Reaction [RT-PCR])	1.53 percentage of participants	0.71 percentage of participants	1.73 percentage of participants

SECONDARY outcome

Timeframe: Up to 24 Weeks

WHO-defined ILI with RT-PCR confirmed influenza A

Outcome measures

Outcome measures
Measure	VIR-2482 (450 mg) n=981 Participants VIR-2482 (450 mg): VIR-2482 450 mg given by intramuscular injection	VIR-2482 (1200 mg) n=992 Participants VIR-2482 (1200 mg): VIR-2482 1200 mg given by intramuscular injection	Placebo n=983 Participants Placebo: Sterile 0.9% (w/v) sodium chloride solution given by intramuscular injection
Percentage of Participants With WHO-defined Influenza-like Illness (ILI) With Confirmed Influenza A (by Reverse Transcription Polymerase Chain Reaction [RT-PCR])	1.22 percentage of participants	0.6 percentage of participants	1.12 percentage of participants

Adverse Events

VIR-2482 (450 mg)

Serious events: 10 serious events

Other events: 454 other events

Deaths: 2 deaths

VIR-2482 (1200 mg)

Serious events: 13 serious events

Other events: 450 other events

Deaths: 3 deaths

Placebo

Serious events: 9 serious events

Other events: 460 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	VIR-2482 (450 mg) n=981 participants at risk VIR-2482 (450 mg): VIR-2482 450mg given by intramuscular injection	VIR-2482 (1200 mg) n=992 participants at risk VIR-2482 (1200 mg): VIR-2482 1200 mg given by intramuscular injection	Placebo n=983 participants at risk Placebo: Sterile 0.9% (w/v) sodium chloride solution given by intramuscular injection
Infections and infestations Upper respiratory tract infection	24.8% 243/981 • through study completion for each participant, up to approximately 43 weeks	24.7% 245/992 • through study completion for each participant, up to approximately 43 weeks	25.2% 248/983 • through study completion for each participant, up to approximately 43 weeks
Infections and infestations COVID-19	9.5% 93/981 • through study completion for each participant, up to approximately 43 weeks	9.2% 91/992 • through study completion for each participant, up to approximately 43 weeks	10.8% 106/983 • through study completion for each participant, up to approximately 43 weeks
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	9.7% 95/981 • through study completion for each participant, up to approximately 43 weeks	8.8% 87/992 • through study completion for each participant, up to approximately 43 weeks	7.6% 75/983 • through study completion for each participant, up to approximately 43 weeks
Respiratory, thoracic and mediastinal disorders Cough	9.0% 88/981 • through study completion for each participant, up to approximately 43 weeks	8.5% 84/992 • through study completion for each participant, up to approximately 43 weeks	7.3% 72/983 • through study completion for each participant, up to approximately 43 weeks
Infections and infestations Viral infection	5.7% 56/981 • through study completion for each participant, up to approximately 43 weeks	4.8% 48/992 • through study completion for each participant, up to approximately 43 weeks	7.1% 70/983 • through study completion for each participant, up to approximately 43 weeks
Musculoskeletal and connective tissue disorders Myalgia	5.2% 51/981 • through study completion for each participant, up to approximately 43 weeks	3.6% 36/992 • through study completion for each participant, up to approximately 43 weeks	3.9% 38/983 • through study completion for each participant, up to approximately 43 weeks

Additional Information

Study Inquiry

Vir Biotechnology, Inc.

Phone: 415-654-5281

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	VIR-2482 (450 mg) n=981 participants at risk VIR-2482 (450 mg): VIR-2482 450mg given by intramuscular injection	VIR-2482 (1200 mg) n=992 participants at risk VIR-2482 (1200 mg): VIR-2482 1200 mg given by intramuscular injection	Placebo n=983 participants at risk Placebo: Sterile 0.9% (w/v) sodium chloride solution given by intramuscular injection
Infections and infestations Appendicitis	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Infections and infestations COVID-19	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Infections and infestations Cellulitis	0.10% 1/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Infections and infestations Pneumonia	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Infections and infestations Urinary tract infection	0.10% 1/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Infections and infestations Appendicitis perforated	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/983 • through study completion for each participant, up to approximately 43 weeks
Infections and infestations Pneumonia klebsiella	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/983 • through study completion for each participant, up to approximately 43 weeks
Injury, poisoning and procedural complications Accidental overdose	0.10% 1/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Injury, poisoning and procedural complications Burns second degree	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Injury, poisoning and procedural complications Injury	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Injury, poisoning and procedural complications Intentional overdose	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Injury, poisoning and procedural complications Splenic rupture	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Injury, poisoning and procedural complications Traumatic fracture	0.10% 1/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Cardiac disorders Acute myocardial infarction	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Cardiac disorders Arrhythmia	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Cardiac disorders Cardiac failure congestive	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Cardiac disorders Cardio-respiratory arrest	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Psychiatric disorders Acute psychosis	0.10% 1/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Psychiatric disorders Completed suicide	0.10% 1/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Psychiatric disorders Conversion disorder	0.10% 1/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Psychiatric disorders Major depression	0.10% 1/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Psychiatric disorders Schizoaffective disorder bipolar type	0.10% 1/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Psychiatric disorders Alcohol withdrawal syndrome	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/983 • through study completion for each participant, up to approximately 43 weeks
Gastrointestinal disorders Enteritis	0.10% 1/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Gastrointestinal disorders Peptic ulcer haemorrhage	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Gastrointestinal disorders Abdominal hernia	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/983 • through study completion for each participant, up to approximately 43 weeks
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.20% 2/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Ear and labyrinth disorders Vertigo positional	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Hepatobiliary disorders Cholelithiasis	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Hepatobiliary disorders Biliary dyskinesia	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/983 • through study completion for each participant, up to approximately 43 weeks
Musculoskeletal and connective tissue disorders Cervical spinal stenosis	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/983 • through study completion for each participant, up to approximately 43 weeks
Nervous system disorders Lumbar radiculopathy	0.10% 1/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Nervous system disorders Cerebrovascular accident	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/983 • through study completion for each participant, up to approximately 43 weeks
Nervous system disorders Seizure	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/983 • through study completion for each participant, up to approximately 43 weeks
Reproductive system and breast disorders Uterine malposition	0.10% 1/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Reproductive system and breast disorders Pelvic organ prolapse	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/983 • through study completion for each participant, up to approximately 43 weeks
Vascular disorders Orthostatic hypotension	0.10% 1/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/983 • through study completion for each participant, up to approximately 43 weeks
Vascular disorders Hypertension	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/983 • through study completion for each participant, up to approximately 43 weeks
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/983 • through study completion for each participant, up to approximately 43 weeks
General disorders Drug withdrawal syndrome	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.10% 1/983 • through study completion for each participant, up to approximately 43 weeks
Metabolism and nutrition disorders Dehydration	0.00% 0/981 • through study completion for each participant, up to approximately 43 weeks	0.00% 0/992 • through study completion for each participant, up to approximately 43 weeks	0.20% 2/983 • through study completion for each participant, up to approximately 43 weeks