Trial Outcomes & Findings for Efficacy and Safety of Extended Release and Immediate Release Febuxostat in Participants With Gout (NCT NCT02139046)

NCT ID: NCT02139046

Last Updated: 2016-11-03

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1790 participants
• Primary outcome timeframe: Month 3
• Results posted on: 2016-11-03

Participant Flow

Participants took part in the study at 217 investigative sites in the United States from 18 April 2014 to 18 November 2015.

Participants with a diagnosis of gout were enrolled equally in 1 of 5 treatment groups: once a day placebo, febuxostat 40 mg extended release (XR), febuxostat 80 mg XR, febuxostat 40 mg immediate release (IR) or febuxostat 80 mg IR.

Participant milestones

Measure	Placebo Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat IR 40 mg Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day (for participants with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min) or every other day (if eGFR ≥ 15 - ≤ 59 mL/min), or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat XR 40 mg Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat IR 80 mg Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat XR 80 mg Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
Overall Study STARTED	358	359	357	358	358
Overall Study Safety Analysis Set	356	358	355	357	357
Overall Study Full Analysis Set	357	357	355	357	357
Overall Study COMPLETED	296	305	298	290	301
Overall Study NOT COMPLETED	62	54	59	68	57

Reasons for withdrawal

Measure	Placebo Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat IR 40 mg Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day (for participants with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min) or every other day (if eGFR ≥ 15 - ≤ 59 mL/min), or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat XR 40 mg Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat IR 80 mg Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat XR 80 mg Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
Overall Study Pretreatment Event/Adverse Event	9	9	10	13	7
Overall Study Major Protocol Deviation	9	10	16	12	6
Overall Study Lost to Follow-up	13	16	16	18	13
Overall Study Voluntary Withdrawal	20	8	10	15	16
Overall Study Lack of Efficacy	0	1	2	1	2
Overall Study Withdrawal due to a Gout Flare	1	1	1	0	1
Overall Study Other Miscellaneous Reasons	10	9	4	9	12

Baseline Characteristics

Efficacy and Safety of Extended Release and Immediate Release Febuxostat in Participants With Gout

Baseline characteristics by cohort

Measure	Placebo n=357 Participants Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat IR 40 mg n=357 Participants Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day (for participants with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min) or every other day (if eGFR ≥ 15 - ≤ 59 mL/min), or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat XR 40 mg n=355 Participants Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat IR 80 mg n=357 Participants Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat XR 80 mg n=357 Participants Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Total n=1783 Participants Total of all reporting groups
Age, Continuous	54.4 years STANDARD_DEVIATION 11.55 • n=5 Participants	55.5 years STANDARD_DEVIATION 11.07 • n=7 Participants	55.1 years STANDARD_DEVIATION 12.68 • n=5 Participants	54.9 years STANDARD_DEVIATION 11.32 • n=4 Participants	55.4 years STANDARD_DEVIATION 11.93 • n=21 Participants	55.1 years STANDARD_DEVIATION 11.71 • n=8 Participants
Age, Customized < 45 years	71 participants n=5 Participants	58 participants n=7 Participants	74 participants n=5 Participants	68 participants n=4 Participants	61 participants n=21 Participants	332 participants n=8 Participants
Age, Customized 45 to < 65 years	223 participants n=5 Participants	225 participants n=7 Participants	193 participants n=5 Participants	219 participants n=4 Participants	222 participants n=21 Participants	1082 participants n=8 Participants
Age, Customized >= 65 years	63 participants n=5 Participants	74 participants n=7 Participants	88 participants n=5 Participants	70 participants n=4 Participants	74 participants n=21 Participants	369 participants n=8 Participants
Age, Customized 18 to < 65 years	294 participants n=5 Participants	283 participants n=7 Participants	267 participants n=5 Participants	287 participants n=4 Participants	283 participants n=21 Participants	1414 participants n=8 Participants
Age, Customized 65 to < 85 years	60 participants n=5 Participants	73 participants n=7 Participants	86 participants n=5 Participants	69 participants n=4 Participants	73 participants n=21 Participants	361 participants n=8 Participants
Age, Customized >= 85 years	3 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	1 participants n=4 Participants	1 participants n=21 Participants	8 participants n=8 Participants
Sex: Female, Male Female	41 Participants n=5 Participants	46 Participants n=7 Participants	43 Participants n=5 Participants	42 Participants n=4 Participants	34 Participants n=21 Participants	206 Participants n=8 Participants
Sex: Female, Male Male	316 Participants n=5 Participants	311 Participants n=7 Participants	312 Participants n=5 Participants	315 Participants n=4 Participants	323 Participants n=21 Participants	1577 Participants n=8 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 participants n=5 Participants	2 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	3 participants n=21 Participants	7 participants n=8 Participants
Race/Ethnicity, Customized Asian	23 participants n=5 Participants	19 participants n=7 Participants	22 participants n=5 Participants	23 participants n=4 Participants	25 participants n=21 Participants	112 participants n=8 Participants
Race/Ethnicity, Customized Black or African American	94 participants n=5 Participants	89 participants n=7 Participants	100 participants n=5 Participants	98 participants n=4 Participants	93 participants n=21 Participants	474 participants n=8 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	3 participants n=5 Participants	5 participants n=7 Participants	4 participants n=5 Participants	3 participants n=4 Participants	5 participants n=21 Participants	20 participants n=8 Participants
Race/Ethnicity, Customized White	231 participants n=5 Participants	235 participants n=7 Participants	226 participants n=5 Participants	230 participants n=4 Participants	225 participants n=21 Participants	1147 participants n=8 Participants
Race/Ethnicity, Customized Other: Multi-Racial	5 participants n=5 Participants	7 participants n=7 Participants	3 participants n=5 Participants	2 participants n=4 Participants	6 participants n=21 Participants	23 participants n=8 Participants
Race/Ethnicity, Customized Hispanic or Latino	53 participants n=5 Participants	51 participants n=7 Participants	61 participants n=5 Participants	49 participants n=4 Participants	52 participants n=21 Participants	266 participants n=8 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	304 participants n=5 Participants	306 participants n=7 Participants	294 participants n=5 Participants	308 participants n=4 Participants	305 participants n=21 Participants	1517 participants n=8 Participants
Region of Enrollment United States	357 participants n=5 Participants	357 participants n=7 Participants	355 participants n=5 Participants	357 participants n=4 Participants	357 participants n=21 Participants	1783 participants n=8 Participants
Height	175.2 cm STANDARD_DEVIATION 9.95 • n=5 Participants	174.8 cm STANDARD_DEVIATION 10.46 • n=7 Participants	174.4 cm STANDARD_DEVIATION 10.45 • n=5 Participants	174.3 cm STANDARD_DEVIATION 9.42 • n=4 Participants	175.3 cm STANDARD_DEVIATION 9.50 • n=21 Participants	174.8 cm STANDARD_DEVIATION 9.96 • n=8 Participants
Weight	106.83 kg STANDARD_DEVIATION 25.285 • n=5 Participants	104.65 kg STANDARD_DEVIATION 24.157 • n=7 Participants	104.71 kg STANDARD_DEVIATION 27.995 • n=5 Participants	102.16 kg STANDARD_DEVIATION 22.832 • n=4 Participants	104.64 kg STANDARD_DEVIATION 23.033 • n=21 Participants	104.60 kg STANDARD_DEVIATION 24.745 • n=8 Participants
Body Mass Index (BMI)	34.88 kg/m^2 STANDARD_DEVIATION 8.276 • n=5 Participants	34.32 kg/m^2 STANDARD_DEVIATION 8.014 • n=7 Participants	34.29 kg/m^2 STANDARD_DEVIATION 8.141 • n=5 Participants	33.68 kg/m^2 STANDARD_DEVIATION 7.477 • n=4 Participants	34.08 kg/m^2 STANDARD_DEVIATION 7.205 • n=21 Participants	34.25 kg/m^2 STANDARD_DEVIATION 7.834 • n=8 Participants
Smoking History Never Smoked	191 participants n=5 Participants	190 participants n=7 Participants	185 participants n=5 Participants	190 participants n=4 Participants	205 participants n=21 Participants	961 participants n=8 Participants
Smoking History Current Smoker	58 participants n=5 Participants	56 participants n=7 Participants	60 participants n=5 Participants	65 participants n=4 Participants	47 participants n=21 Participants	286 participants n=8 Participants
Smoking History Ex-Smoker	108 participants n=5 Participants	111 participants n=7 Participants	110 participants n=5 Participants	102 participants n=4 Participants	105 participants n=21 Participants	536 participants n=8 Participants
Alcohol Classification Never Drank	81 participants n=5 Participants	92 participants n=7 Participants	85 participants n=5 Participants	68 participants n=4 Participants	74 participants n=21 Participants	400 participants n=8 Participants
Alcohol Classification Current Drinker	234 participants n=5 Participants	204 participants n=7 Participants	218 participants n=5 Participants	234 participants n=4 Participants	232 participants n=21 Participants	1122 participants n=8 Participants
Alcohol Classification Ex-Drinker	42 participants n=5 Participants	61 participants n=7 Participants	52 participants n=5 Participants	55 participants n=4 Participants	51 participants n=21 Participants	261 participants n=8 Participants

PRIMARY outcome

Timeframe: Month 3

Population: Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of double-blind study medication. Participants who discontinued double-blind study drug prior to the Month 3 visit were considered treatment failures, i.e. to have serum urate ≥ 5.0 mg/dL.

Outcome measures

Measure	Placebo n=357 Participants Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat IR 40 mg n=357 Participants Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day (for participants with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min) or every other day (if eGFR ≥ 15 - ≤ 59 mL/min), or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat XR 40 mg n=355 Participants Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat IR 80 mg n=357 Participants Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat XR 80 mg n=357 Participants Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
Percentage of Participants With Serum Urate <5.0 mg/dL at Month 3	0.3 percentage of participants	15.7 percentage of participants	25.9 percentage of participants	42.6 percentage of participants	50.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Month 3

Population: FAS included all participants who were randomized and received at least 1 dose of double-blind study medication.

A participant was considered to have a gout flare if the following criteria were met:

Participant-reported acute particular pain typical of a gout attack that was deemed by participant and/or investigator to require treatment and was treated with colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs) or steroids, Participant experienced at least 3 or more of: 1) Joint swelling, 2) Redness, 3) Tenderness, 4) Pain, Participant experienced at least one or more of: 1) Rapid onset of pain, 2) Decreased range of motion, 3) Joint warmth, 4) Other symptoms similar to a prior gout flare.

Outcome measures

Measure	Placebo n=357 Participants Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat IR 40 mg n=357 Participants Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day (for participants with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min) or every other day (if eGFR ≥ 15 - ≤ 59 mL/min), or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat XR 40 mg n=355 Participants Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat IR 80 mg n=357 Participants Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat XR 80 mg n=357 Participants Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
Percentage of Participants With at Least One Gout Flare Requiring Treatment	20.7 percentage of participants	21.0 percentage of participants	22.8 percentage of participants	27.2 percentage of participants	26.6 percentage of participants

SECONDARY outcome

Timeframe: Month 3

Population: FAS included all participants who were randomized and received at least 1 dose of double-blind study medication. Participants who discontinued double-blind study drug prior to the Month 3 visit were considered treatment failures, i.e. to have serum urate ≥ 5.0 mg/dL.

Outcome measures

Measure	Placebo n=357 Participants Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat IR 40 mg n=357 Participants Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day (for participants with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min) or every other day (if eGFR ≥ 15 - ≤ 59 mL/min), or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat XR 40 mg n=355 Participants Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat IR 80 mg n=357 Participants Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat XR 80 mg n=357 Participants Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
Percentage of Participants With Serum Urate <6.0 mg/dL at Month 3	0.6 percentage of participants	40.3 percentage of participants	48.2 percentage of participants	57.7 percentage of participants	61.1 percentage of participants

Adverse Events

Placebo

Serious events: 8 serious events

Other events: 53 other events

Deaths: 0 deaths

Febuxostat IR 40 mg

Serious events: 12 serious events

Other events: 53 other events

Deaths: 0 deaths

Febuxostat XR 40 mg

Serious events: 6 serious events

Other events: 45 other events

Deaths: 0 deaths

Febuxostat IR 80 mg

Serious events: 8 serious events

Other events: 55 other events

Deaths: 0 deaths

Febuxostat XR 80 mg

Serious events: 8 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=356 participants at risk Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat IR 40 mg n=358 participants at risk Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day (for participants with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min) or every other day (if eGFR ≥ 15 - ≤ 59 mL/min), or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat XR 40 mg n=355 participants at risk Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat IR 80 mg n=357 participants at risk Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat XR 80 mg n=357 participants at risk Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
Gastrointestinal disorders Nausea	0.28% 1/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Vomiting	0.28% 1/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Cardiac disorders Hypertensive heart disease	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Cardiac disorders Cardiac failure congestive	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Cardiac disorders Acute myocardial infarction	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Cardiac disorders Atrial fibrillation	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Cardiac disorders Sinus node dysfunction	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Cardiac disorders Cardiac arrest	0.28% 1/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Pancreatitis	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.28% 1/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Gastrointestinal disorders Abdominal pain	0.56% 2/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
General disorders Malaise	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
General disorders Oedema peripheral	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
General disorders Non-cardiac chest pain	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Infections and infestations Abdominal abscess	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Infections and infestations Amoebiasis	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Infections and infestations Influenza	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Infections and infestations Pneumonia	0.28% 1/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Infections and infestations Viral infection	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Injury, poisoning and procedural complications Road traffic accident	0.28% 1/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Metabolism and nutrition disorders Gout	0.28% 1/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Metabolism and nutrition disorders Hyperkalaemia	0.28% 1/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Metabolism and nutrition disorders Dehydration	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Musculoskeletal and connective tissue disorders Gouty arthritis	0.28% 1/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tongue neoplasm malignant stage unspecified	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.28% 1/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Nervous system disorders Basal ganglia stroke	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Nervous system disorders Ischaemic stroke	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Nervous system disorders Hypoglycaemic unconsciousness	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Nervous system disorders Hemiparesis	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Psychiatric disorders Bipolar I disorder	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Renal and urinary disorders Acute kidney injury	0.28% 1/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.56% 2/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Renal and urinary disorders Renal failure	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Renal and urinary disorders Renal impairment	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Vascular disorders Hypertension	0.28% 1/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.00% 0/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.

Other adverse events

Measure	Placebo n=356 participants at risk Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat IR 40 mg n=358 participants at risk Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day (for participants with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min) or every other day (if eGFR ≥ 15 - ≤ 59 mL/min), or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat XR 40 mg n=355 participants at risk Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat IR 80 mg n=357 participants at risk Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.	Febuxostat XR 80 mg n=357 participants at risk Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
Gastrointestinal disorders Diarrhoea	3.7% 13/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	2.5% 9/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	2.5% 9/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	5.9% 21/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	2.5% 9/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Infections and infestations Nasopharyngitis	3.1% 11/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	2.0% 7/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	2.0% 7/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	2.5% 9/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	1.1% 4/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Infections and infestations Upper respiratory tract infection	1.1% 4/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	1.7% 6/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	1.7% 6/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	1.4% 5/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	2.2% 8/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Investigations Alanine aminotransferase increased	1.7% 6/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	2.0% 7/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	2.3% 8/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.56% 2/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	1.1% 4/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Musculoskeletal and connective tissue disorders Arthralgia	2.0% 7/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	2.2% 8/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	1.4% 5/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	1.7% 6/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	1.1% 4/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Nervous system disorders Headache	1.7% 6/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	1.7% 6/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	2.3% 8/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	1.1% 4/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	1.1% 4/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Respiratory, thoracic and mediastinal disorders Cough	1.4% 5/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	2.5% 9/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.56% 2/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.84% 3/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	0.28% 1/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.
Vascular disorders Hypertension	2.5% 9/356 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	3.6% 13/358 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	1.7% 6/355 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	2.2% 8/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.	1.4% 5/357 • First dose of double-blind study drug to 30 days past last dose of double-blind study drug (Up to 4 Months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings reported by the participant or observed by the investigator, irrespective of the relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of double-blind study medication.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

Results disclosure agreements

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

Restriction type: OTHER