Trial Outcomes & Findings for Parallel-Group Comparison of Olmesartan (OLM), Amlodipine (AML) and Hydrochlorothiazid (HCTZ) in Hypertension (NCT NCT00923091)

Last Updated: 2019-01-10

Results Overview

Baseline blood pressure was defined as the average values obtained at the randomization visit and at the visit prior to randomization

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2689 participants

Primary outcome timeframe

Baseline to week 10

Results posted on

2019-01-10

Participant Flow

This study was conduct in Europe from 27 May 2009 to 12 January 2011

Study has randomised, double-blind, placebo-controlled parallel-group portion (Periods I-II) followed by transition phase (Periods III-V) wherein combination titration steps were evaluated in subjects not achieving blood pressure goals. The transition required that all be entered into Period 3 on olm/aml/hctz 20/5/12.5 to ensure a common baseline.

Participant milestones

Participant milestones
Measure	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5mg Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion. In Period III, all participants were included in this group. Responders (a participant was considered a responder if their blood pressure was \<140/90 mm Hg; \<130/80 mm Hg if the participant had diabetes or chronic renal or cardiovascular disease) in Period III went directly to Period VI. In Period IV participants who did not meet the blood pressure goals in Period III were randomized in a 1:2 fashion to this group or the OLM/AML/HCTZ 40/5/12.5 group.	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion. In Period IV participants who did not meet the blood pressure goals (\<140/90 mm Hg; or \<130/80 for participants with diabetes or chronic renal or cardiovascular disease)in Period III were randomized in a 1:2 fashion to OLM/AML/HCTZ 20/5/12.5 or this group.	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 2 tablets of hydroclororthiazide 12.5 mg. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion.	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion.	Olmesartan/Amlodipine/Hydrochlorothiazide(HCT) 40mg/10mg/25mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 2 tablets of hydroclororthiazide 12.5 mg. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion.	Olmesartan(OM)20mg/Amlodipine (AML)5mg Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion.	Olmesartan/Amlodipine 40mg/5mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion.	Olmesartan/Amlodipine 40mg/10mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + two 12.5 mg hydrochlorothiazide placebo tablets. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion.	OM/AML/HCT 40/5/12.5mg Responder Continued on 40/5/12.5 mg In Period V responders continued on olmesartan/amlodipine/ hydrochlorothiazide 40mg/5mg/12.5 mg. A participant was considered a responder if their blood pressure was \<140/90 mm Hg; \<130/80 mm Hg if the participant had diabetes or chronic renal or cardiovascular disease.	OM/AML/HCT 40/5/12.5mg Non Responder Randomized to 40/5/12.5mg In Period V OLM/AML/HCTZ 40/5/12.5 non-responders were randomized to olmesartan/amlodipine/hydrochlorothiazide 40mg/5mg/12.5 mg or to 40mg/5mg/25 mg. A participant was considered a responder if their blood pressure was \<140/90 mm Hg; \<130/80 mm Hg if the participant had diabetes or chronic renal or cardiovascular disease.	OM/AML/HCT 40/5/12.5mg Non Responder Randomized to 40/5/25mg In Period V OLM/AML/HCTZ 40/5/12.5 non-responders were randomized to olmesartan/amlodipine/hydrochlorothiazide 40mg/5mg/12.5 mg or to 40mg/5mg/25 mg. A participant was considered a responder if their blood pressure was \<140/90 mm Hg; \<130/80 mm Hg if the participant had diabetes or chronic renal or cardiovascular disease.	OM/AML/HCT 20/5/12.5mg NonResponder Up Titrated to 40/5/12.5mg In Period V non-responders to olmesartan/amlodipine/hydrochlorothiazide 20mg/5mg/12.5 mg were up titrated to 40mg/5mg/12.5mg. A participant was considered a responder if their blood pressure was \<140/90 mm Hg; \<130/80 mm Hg if the participant had diabetes or chronic renal or cardiovascular disease.	20/5/12.5mg Responder Continued on 20/5/12.5 mg In Period V non-responders to olmesartan/amlodipine/hydrochlorothiazide 20mg/5mg/12.5 mg continued on 20mg/5mg/12.5mg. A participant was considered a responder if their blood pressure was \<140/90 mm Hg; \<130/80 mm Hg if the participant had diabetes or chronic renal or cardiovascular disease.
PeriodI-II (Randomized, Double-Blind) STARTED	335	336	336	336	336	337	337	336	0	0	0	0	0
PeriodI-II (Randomized, Double-Blind) COMPLETED	319	325	323	309	315	322	319	311	0	0	0	0	0
PeriodI-II (Randomized, Double-Blind) NOT COMPLETED	16	11	13	27	21	15	18	25	0	0	0	0	0
Period III (Single-Blind) STARTED	2540	0	0	0	0	0	0	0	0	0	0	0	0
Period III (Single-Blind) COMPLETED	2520	0	0	0	0	0	0	0	0	0	0	0	0
Period III (Single-Blind) NOT COMPLETED	20	0	0	0	0	0	0	0	0	0	0	0	0
Period IV (Double-Blind) STARTED	228	453	0	0	0	0	0	0	0	0	0	0	0
Period IV (Double-Blind) COMPLETED	226	451	0	0	0	0	0	0	0	0	0	0	0
Period IV (Double-Blind) NOT COMPLETED	2	2	0	0	0	0	0	0	0	0	0	0	0
Period V (Double -Blind) STARTED	0	0	0	0	0	0	0	0	135	119	194	151	75
Period V (Double -Blind) COMPLETED	0	0	0	0	0	0	0	0	134	119	193	151	73
Period V (Double -Blind) NOT COMPLETED	0	0	0	0	0	0	0	0	1	0	1	0	2
Period VI (Open-Label) STARTED	1447	272	480	146	164	0	0	0	0	0	0	0	0
Period VI (Open-Label) COMPLETED	1408	264	467	143	157	0	0	0	0	0	0	0	0
Period VI (Open-Label) NOT COMPLETED	39	8	13	3	7	0	0	0	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5mg Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion. In Period III, all participants were included in this group. Responders (a participant was considered a responder if their blood pressure was \<140/90 mm Hg; \<130/80 mm Hg if the participant had diabetes or chronic renal or cardiovascular disease) in Period III went directly to Period VI. In Period IV participants who did not meet the blood pressure goals in Period III were randomized in a 1:2 fashion to this group or the OLM/AML/HCTZ 40/5/12.5 group.	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion. In Period IV participants who did not meet the blood pressure goals (\<140/90 mm Hg; or \<130/80 for participants with diabetes or chronic renal or cardiovascular disease)in Period III were randomized in a 1:2 fashion to OLM/AML/HCTZ 20/5/12.5 or this group.	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 2 tablets of hydroclororthiazide 12.5 mg. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion.	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion.	Olmesartan/Amlodipine/Hydrochlorothiazide(HCT) 40mg/10mg/25mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 2 tablets of hydroclororthiazide 12.5 mg. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion.	Olmesartan(OM)20mg/Amlodipine (AML)5mg Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion.	Olmesartan/Amlodipine 40mg/5mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion.	Olmesartan/Amlodipine 40mg/10mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + two 12.5 mg hydrochlorothiazide placebo tablets. In Periods I/II participants were randomized to this and the other 7 arms arms in a 1:1:1:1:1:1:1:1 fashion.	OM/AML/HCT 40/5/12.5mg Responder Continued on 40/5/12.5 mg In Period V responders continued on olmesartan/amlodipine/ hydrochlorothiazide 40mg/5mg/12.5 mg. A participant was considered a responder if their blood pressure was \<140/90 mm Hg; \<130/80 mm Hg if the participant had diabetes or chronic renal or cardiovascular disease.	OM/AML/HCT 40/5/12.5mg Non Responder Randomized to 40/5/25mg In Period V OLM/AML/HCTZ 40/5/12.5 non-responders were randomized to olmesartan/amlodipine/hydrochlorothiazide 40mg/5mg/12.5 mg or to 40mg/5mg/25 mg. A participant was considered a responder if their blood pressure was \<140/90 mm Hg; \<130/80 mm Hg if the participant had diabetes or chronic renal or cardiovascular disease.	20/5/12.5mg Responder Continued on 20/5/12.5 mg In Period V non-responders to olmesartan/amlodipine/hydrochlorothiazide 20mg/5mg/12.5 mg continued on 20mg/5mg/12.5mg. A participant was considered a responder if their blood pressure was \<140/90 mm Hg; \<130/80 mm Hg if the participant had diabetes or chronic renal or cardiovascular disease.
PeriodI-II (Randomized, Double-Blind) Adverse Event	11	3	7	13	10	5	9	17	0	0	0
PeriodI-II (Randomized, Double-Blind) Withdrawal by Subject	4	6	5	8	7	6	5	5	0	0	0
PeriodI-II (Randomized, Double-Blind) Protocol Violation	1	1	1	5	4	2	4	3	0	0	0
PeriodI-II (Randomized, Double-Blind) Lost to Follow-up	0	0	0	0	0	1	0	0	0	0	0
PeriodI-II (Randomized, Double-Blind) Other Reason	0	1	0	1	0	1	0	0	0	0	0
Period III (Single-Blind) Adverse Event	5	0	0	0	0	0	0	0	0	0	0
Period III (Single-Blind) Withdrawal by Subject	10	0	0	0	0	0	0	0	0	0	0
Period III (Single-Blind) Protocol Violation	3	0	0	0	0	0	0	0	0	0	0
Period III (Single-Blind) Lost to Follow-up	2	0	0	0	0	0	0	0	0	0	0
Period IV (Double-Blind) Adverse Event	2	0	0	0	0	0	0	0	0	0	0
Period IV (Double-Blind) Withdrawal by Subject	0	1	0	0	0	0	0	0	0	0	0
Period IV (Double-Blind) Protocol Violation	0	1	0	0	0	0	0	0	0	0	0
Period V (Double -Blind) Withdrawal by Subject	0	0	0	0	0	0	0	0	1	0	1
Period V (Double -Blind) Protocol Violation	0	0	0	0	0	0	0	0	0	0	1
Period V (Double -Blind) Lost to Follow-up	0	0	0	0	0	0	0	0	0	1	0
Period VI (Open-Label) Adverse Event	17	0	4	1	1	0	0	0	0	0	0
Period VI (Open-Label) Withdrawal by Subject	15	7	5	0	1	0	0	0	0	0	0
Period VI (Open-Label) Protocol Violation	6	1	3	1	4	0	0	0	0	0	0
Period VI (Open-Label) Lost to Follow-up	1	0	1	0	0	0	0	0	0	0	0
Period VI (Open-Label) Other Reason	0	0	0	1	1	0	0	0	0	0	0

Baseline Characteristics

Parallel-Group Comparison of Olmesartan (OLM), Amlodipine (AML) and Hydrochlorothiazid (HCTZ) in Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg n=335 Participants	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg n=336 Participants	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg n=336 Participants	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg n=336 Participants	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg n=336 Participants	Olmesartan/Amlodipine 20mg/5mg n=337 Participants	Olmesartan/Amlodipine 40mg/5mg n=337 Participants	Olmesartan/Amlodipine 40mg/10mg n=336 Participants	Total n=2689 Participants Total of all reporting groups
Age, Continuous	56.0 years STANDARD_DEVIATION 10.81 • n=93 Participants	56.8 years STANDARD_DEVIATION 10.36 • n=4 Participants	56.5 years STANDARD_DEVIATION 10.92 • n=27 Participants	57.0 years STANDARD_DEVIATION 10.72 • n=483 Participants	55.9 years STANDARD_DEVIATION 11.08 • n=36 Participants	56.1 years STANDARD_DEVIATION 10.22 • n=10 Participants	56.4 years STANDARD_DEVIATION 10.4 • n=115 Participants	57.0 years STANDARD_DEVIATION 9.70 • n=40 Participants	56.5 years STANDARD_DEVIATION 10.53 • n=8 Participants
Sex: Female, Male Female	182 Participants n=93 Participants	171 Participants n=4 Participants	184 Participants n=27 Participants	181 Participants n=483 Participants	178 Participants n=36 Participants	185 Participants n=10 Participants	170 Participants n=115 Participants	192 Participants n=40 Participants	1443 Participants n=8 Participants
Sex: Female, Male Male	153 Participants n=93 Participants	165 Participants n=4 Participants	152 Participants n=27 Participants	155 Participants n=483 Participants	158 Participants n=36 Participants	152 Participants n=10 Participants	167 Participants n=115 Participants	144 Participants n=40 Participants	1246 Participants n=8 Participants
Race/Ethnicity, Customized Asian	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	1 Participants n=40 Participants	3 Participants n=8 Participants
Race/Ethnicity, Customized Black	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	1 Participants n=8 Participants
Race/Ethnicity, Customized White	334 Participants n=93 Participants	336 Participants n=4 Participants	335 Participants n=27 Participants	335 Participants n=483 Participants	336 Participants n=36 Participants	337 Participants n=10 Participants	337 Participants n=115 Participants	335 Participants n=40 Participants	2685 Participants n=8 Participants
Region of Enrollment Europe	335 Participants n=93 Participants	336 Participants n=4 Participants	336 Participants n=27 Participants	336 Participants n=483 Participants	336 Participants n=36 Participants	337 Participants n=10 Participants	337 Participants n=115 Participants	336 Participants n=40 Participants	2689 Participants n=8 Participants

PRIMARY outcome

Timeframe: Baseline to week 10

Population: The full analysis set includes 2679 randomized patients who received at least 1 dose of double-blind medication and who provided at least one diastolic blood pressure measurement in Period I-II

Baseline blood pressure was defined as the average values obtained at the randomization visit and at the visit prior to randomization

Outcome measures

Outcome measures
Measure	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg n=334 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg n=336 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg n=335 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 2 tablets of hydroclororthiazide 12.5 mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg n=336 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg n=332 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 2 tablets of hydroclororthiazide 12.5 mg	Olmesartan/Amlodipine 20mg/5mg n=337 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Olmesartan/Amlodipine 40mg/5mg n=334 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Olmesartan/Amlodipine 40mg/10mg n=335 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + two 12.5 mg hydrochlorothiazide placebo tablets
Change in Seated Diastolic Blood Pressure (SeDBP).	-22.5 mm HG Standard Error 0.48	-22.5 mm HG Standard Error 0.48	-23.0 mm HG Standard Error 0.48	-23.9 mm HG Standard Error 0.47	-23.8 mm HG Standard Error 0.48	-20.5 mm HG Standard Error 0.47	-21.2 mm HG Standard Error 0.48	-22.1 mm HG Standard Error 0.48

SECONDARY outcome

Timeframe: Baseline to week 10

Outcome measures

Outcome measures
Measure	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg n=334 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg n=336 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg n=335 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 2 tablets of hydroclororthiazide 12.5 mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg n=336 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg n=332 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 2 tablets of hydroclororthiazide 12.5 mg	Olmesartan/Amlodipine 20mg/5mg n=337 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Olmesartan/Amlodipine 40mg/5mg n=334 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Olmesartan/Amlodipine 40mg/10mg n=335 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + two 12.5 mg hydrochlorothiazide placebo tablets
Change in Seated Systolic Blood Pressure (SeDBP).	-33.2 mm Hg Standard Error 0.72	-33.7 mm Hg Standard Error 0.72	-35.3 mm Hg Standard Error 0.71	-35.5 mm Hg Standard Error 0.71	-36.2 mm Hg Standard Error 0.72	-29.9 mm Hg Standard Error 0.71	-30.4 mm Hg Standard Error 0.71	-32.8 mm Hg Standard Error 0.71

SECONDARY outcome

Timeframe: baseline to week 10

Blood pressure treatment goal was defined as blood pressure \<140/90 mmHg or \<130/80 mmHg for subjects with diabetes, chronic renal disease, or chronic cardiovascular disease.

Outcome measures

Outcome measures
Measure	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg n=334 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg n=336 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg n=335 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 2 tablets of hydroclororthiazide 12.5 mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg n=336 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg n=332 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 2 tablets of hydroclororthiazide 12.5 mg	Olmesartan/Amlodipine 20mg/5mg n=337 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Olmesartan/Amlodipine 40mg/5mg n=334 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Olmesartan/Amlodipine 40mg/10mg n=335 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + two 12.5 mg hydrochlorothiazide placebo tablets
Number of Subjects Reaching Blood Pressure Goal at Week 10	177 Participants	176 Participants	197 Participants	190 Participants	179 Participants	144 Participants	155 Participants	166 Participants

SECONDARY outcome

Timeframe: Week 18 to week 22

Population: The Full Analysis Set 2=681 randomized participants who received at least 1 dose of double-blind medication and who provided at least one diastolic blood pressure measurement in Period IV

Outcome measures

Outcome measures
Measure	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg n=228 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg n=453 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 2 tablets of hydroclororthiazide 12.5 mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 2 tablets of hydroclororthiazide 12.5 mg	Olmesartan/Amlodipine 20mg/5mg Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Olmesartan/Amlodipine 40mg/5mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Olmesartan/Amlodipine 40mg/10mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + two 12.5 mg hydrochlorothiazide placebo tablets
Change in Seated Diastolic Blood Pressure From Week 18 to Week 22	-3.3 mm Hg Standard Error 0.47	-4.1 mm Hg Standard Error 0.37	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 18 to week 22

Population: The Full Analysis Set 2=681 randomized participants who received at least 1 dose of double-blind medication and who provided at least one blood pressure measurement in Period IV

Outcome measures

Outcome measures
Measure	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg n=228 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg n=453 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 2 tablets of hydroclororthiazide 12.5 mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 2 tablets of hydroclororthiazide 12.5 mg	Olmesartan/Amlodipine 20mg/5mg Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Olmesartan/Amlodipine 40mg/5mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Olmesartan/Amlodipine 40mg/10mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + two 12.5 mg hydrochlorothiazide placebo tablets
Change in Seated Systolic Blood Pressure From Week 18 to Week 22	-5.7 mm Hg Standard Error 0.71	-6.5 mm Hg Standard Error 0.56	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 18 to week 22

Population: The Full Analysis Set 2=681 randomized participants who received at least 1 dose of double-blind medication and who provided at least one diastolic blood pressure measurement in Period IV

Blood pressure treatment goal was defined as blood pressure \<140/90 mmHg or \<130/80 mmHg for subjects with diabetes, chronic renal disease, or chronic cardiovascular disease.

Outcome measures

Outcome measures
Measure	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg n=228 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg n=453 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 2 tablets of hydroclororthiazide 12.5 mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 2 tablets of hydroclororthiazide 12.5 mg	Olmesartan/Amlodipine 20mg/5mg Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Olmesartan/Amlodipine 40mg/5mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Olmesartan/Amlodipine 40mg/10mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + two 12.5 mg hydrochlorothiazide placebo tablets
Number of Subjects Reaching Blood Pressure Goal From Week 18 to Week 22	63 Participants	137 Participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 22 to week 26

Population: The Full Analysis Set 3=312 randomized participants who received at least one dose of double-blind medication and who provided at least one diastolic blood pressure measurement in Period V.

Outcome measures

Outcome measures
Measure	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg n=119 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg n=193 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 2 tablets of hydroclororthiazide 12.5 mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 2 tablets of hydroclororthiazide 12.5 mg	Olmesartan/Amlodipine 20mg/5mg Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Olmesartan/Amlodipine 40mg/5mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Olmesartan/Amlodipine 40mg/10mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + two 12.5 mg hydrochlorothiazide placebo tablets
Change in Seated Diastolic Blood Pressure From Week 22 to Week 26	-2.7 mm Hg Standard Error 0.68	-3.8 mm Hg Standard Error 0.56	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 22 to week 26

Outcome measures

Outcome measures
Measure	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg n=119 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg n=193 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 2 tablets of hydroclororthiazide 12.5 mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 2 tablets of hydroclororthiazide 12.5 mg	Olmesartan/Amlodipine 20mg/5mg Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Olmesartan/Amlodipine 40mg/5mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Olmesartan/Amlodipine 40mg/10mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + two 12.5 mg hydrochlorothiazide placebo tablets
Change in Seated Systolic Blood Pressure From Week 22 to Week 26	-4.5 mm Hg Standard Error 1.01	-6.7 mm Hg Standard Error 0.84	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 22 to week 26

Blood pressure treatment goal was defined as blood pressure \<140/90 mmHg or \<130/80 mmHg for subjects with diabetes, chronic renal disease, or chronic cardiovascular disease.

Outcome measures

Outcome measures
Measure	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg n=119 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg n=193 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 2 tablets of hydroclororthiazide 12.5 mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 2 tablets of hydroclororthiazide 12.5 mg	Olmesartan/Amlodipine 20mg/5mg Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Olmesartan/Amlodipine 40mg/5mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Olmesartan/Amlodipine 40mg/10mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + two 12.5 mg hydrochlorothiazide placebo tablets
Number of Subjects Reaching Blood Pressure Goal at Week 26	29 Participants	47 Participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 26 to week 54

Population: The number of subjects up titrated who had blood pressure values at both time points.

Outcome measures

Outcome measures
Measure	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg n=87 Participants Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + 2 tablets of hydroclororthiazide 12.5 mg	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 1 tablet of hydroclororthiazide 12.5 mg + one 12.5 mg hydrochlorothiazide placebo tablet	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + 2 tablets of hydroclororthiazide 12.5 mg	Olmesartan/Amlodipine 20mg/5mg Once a day the following tablets were taken: 1 tablet of olmesartan 20 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Olmesartan/Amlodipine 40mg/5mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 5 mg + two 12.5 mg hydrochlorothiazide placebo tablets	Olmesartan/Amlodipine 40mg/10mg Once a day the following tablets were taken: 1 tablet of olmesartan 40 mg/amlodipine 10 mg + two 12.5 mg hydrochlorothiazide placebo tablets
Change in Seated Systolic Blood Pressure (SeDBP) During Open-Label Period VI (Titration Effect From OM/AML/HCTZ 40/5/25 to 40/10/25.	-11.9 mm Hg Standard Deviation 11.01	—	—	—	—	—	—	—

Adverse Events

Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg

Serious events: 55 serious events

Other events: 12 other events

Deaths: 0 deaths

Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg

Serious events: 9 serious events

Other events: 44 other events

Deaths: 0 deaths

Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg

Serious events: 22 serious events

Other events: 13 other events

Deaths: 0 deaths

Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg

Serious events: 3 serious events

Other events: 39 other events

Deaths: 0 deaths

Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg

Serious events: 7 serious events

Other events: 45 other events

Deaths: 0 deaths

Olmesartan/Amlodipine 20mg/5mg

Serious events: 1 serious events

Other events: 26 other events

Deaths: 0 deaths

Olmesartan/Amlodipine 40mg/5mg

Serious events: 5 serious events

Other events: 38 other events

Deaths: 0 deaths

Olmesartan/Amlodipine 40mg/10mg

Serious events: 7 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg n=329 participants at risk	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg n=334 participants at risk	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg n=331 participants at risk	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg n=329 participants at risk	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg n=332 participants at risk	Olmesartan/Amlodipine 20mg/5mg n=333 participants at risk	Olmesartan/Amlodipine 40mg/5mg n=332 participants at risk	Olmesartan/Amlodipine 40mg/10mg n=325 participants at risk
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Gastrointestinal disorders Inguinal hernia	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Investigations Electrocardiogram QRS complex shortened	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Cardiac disorders Tachycardia paroxysmal	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Nervous system disorders Transient ischemic attack	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Cardiac disorders Acute myocardial infarction	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Injury, poisoning and procedural complications Meniscus lesion	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.31% 1/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Gastrointestinal disorders Oesophagitis	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.31% 1/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Cardiac disorders Atrial fibrillation	0.61% 2/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.31% 1/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Cardiac disorders Angina unstable	0.61% 2/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.31% 1/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	1.2% 4/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.31% 1/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Gastrointestinal disorders Gastric Polyps	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Infections and infestations Bronchopneumonia	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Musculoskeletal and connective tissue disorders Torticollis	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Injury, poisoning and procedural complications Tendon rupture	0.61% 2/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Metabolism and nutrition disorders Hypokalemia	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Eye disorders Angle closure glaucoma	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Metabolism and nutrition disorders Diabetes mellitus	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Injury, poisoning and procedural complications Tibia fracture	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Gastrointestinal disorders Pancreatitis chronic	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Vascular disorders Hypertension	0.61% 2/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Injury, poisoning and procedural complications Ankle fracture	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Cardiac disorders Left ventricular failure	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Infections and infestations Pneumonia	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Nervous system disorders Ischaemic stroke	0.61% 2/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.60% 2/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Infections and infestations Sinusitis	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Nervous system disorders Syncope	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Injury, poisoning and procedural complications Barotrauma	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Injury, poisoning and procedural complications Tendon injury	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Eye disorders Cataract	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Gastrointestinal disorders Colonic polyp	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Vascular disorders Arterial thrombosis limb	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Surgical and medical procedures Removal of internal fixation	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Cardiac disorders Myocardial infarction	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.60% 2/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Cardiac disorders Cardiogenic shock	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.31% 1/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Investigations Hepatitus B virus	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Infections and infestations Mediastinitis	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Infections and infestations Pyothorax	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Cardiac disorders Angina pectoris	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Reproductive system and breast disorders Uterine polyp	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Musculoskeletal and connective tissue disorders Back pain	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Infections and infestations Peritonsillar abcess	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Reproductive system and breast disorders Prostatitis	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant fibrous histiocytoma	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Vascular disorders Hypertensive crisis	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Investigations Blood pressure decreased	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Psychiatric disorders Completed suicide	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Nervous system disorders Dizziness	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Injury, poisoning and procedural complications Intentional overdose	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Eye disorders Eye haemorrhage	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Eye disorders Retinal Detachment	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Gastrointestinal disorders Gastritis	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostatic adenoma	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Hepatobiliary disorders Cholecystitis	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Gastrointestinal disorders Mouth cyst	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Eye disorders Ulcerative keratitis	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Injury, poisoning and procedural complications Patella fracture	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Gastrointestinal disorders Ascites	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Cardiac disorders Coronary artery disease	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Renal and urinary disorders Calculus ureteric	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Renal and urinary disorders Hydronephrosis	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Injury, poisoning and procedural complications Vertebral injury	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Nervous system disorders Cerebral ischaemia	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Cardiac disorders Acute coronary syndrome	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Infections and infestations Appendicitis	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Psychiatric disorders Alcohol abuse	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Cardiac disorders Extrasystoles	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	— 0/0 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Injury, poisoning and procedural complications Femeral Neck Fracture	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.30% 1/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.31% 1/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.

Other adverse events

Other adverse events
Measure	Olmesartan/Amlodipine/Hydrochlorothiazide 20mg/5mg/12.5 mg n=329 participants at risk	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/12.5mg n=334 participants at risk	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/5mg/25mg n=331 participants at risk	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/12.5mg n=329 participants at risk	Olmesartan/Amlodipine/Hydrochlorothiazide 40mg/10mg/25mg n=332 participants at risk	Olmesartan/Amlodipine 20mg/5mg n=333 participants at risk	Olmesartan/Amlodipine 40mg/5mg n=332 participants at risk	Olmesartan/Amlodipine 40mg/10mg n=325 participants at risk
General disorders Oedema peripheral	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	4.5% 15/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	7.9% 26/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	8.1% 27/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	3.3% 11/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	4.8% 16/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	9.2% 30/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Nervous system disorders Headache	3.6% 12/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	4.8% 16/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	3.9% 13/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	4.0% 13/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	5.4% 18/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	4.5% 15/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Investigations Nasopharyngitis	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	3.9% 13/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	3.3% 11/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.
Metabolism and nutrition disorders Dyslipidaemia	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/334 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/331 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/329 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/333 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	3.3% 11/332 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.	0.00% 0/325 • Week 1 to week 54 All adverse events, whether observed by the investigator or reported by the participant were recorded on the Adverse Event electronic Case Report Form. Adverse events (AEs)were collected up to 14 days after the last study dose; for serious AEs considered to be drug related there was no time limit.

Additional Information

Bettina Ammentorp

Daiichi Sankyo Europe, GmbH

Phone: 00498978080

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A site may not publish results until after a coordinated multicentre publication has been submitted for publication or until one year after the study has ended, whichever occurs first. Then, the site will have the opportunity to publish the results, provided that DSE has had the opportunity to review and comment on the site's proposed publication prior to its being submitted for publication with the advice of company patent council and in accord with needs for subject protection.
Publication restrictions are in place

Restriction type: OTHER