Trial Outcomes & Findings for Efficacy and Safety Study of R935788 Tablets to Treat Rheumatoid Arthritis (NCT NCT00665925)

Results Overview

The number of participants with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 6 months

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

457 participants

Primary outcome timeframe

6 months

Results posted on

2016-09-16

Participant Flow

The first participant received the first dose of study drug on 19 May 2008; the last participant completed the study on 01 June 2009. Participants were recruited from centers in the United States, Europe and Latin America.

Male/female participants who had active rheumatoid arthritis (RA) for a minimum of 6 months, and receiving a weekly methotrexate (MTX) dose for a minimum of 3 months were randomly assigned to receive R788 150 mg once daily, 100 mg twice daily, placebo once daily or placebo twice daily. It was planned to randomize approximately 420 participants.

Participant milestones

Participant milestones
Measure	Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	R788 150 mg qd R788 150 mg, oral tablets, once daily, double-blind	R788 100 mg Bid R788 100 mg, oral tablets, twice daily, double-blind
Overall Study STARTED	77	76	152	152
Overall Study COMPLETED	62	59	126	131
Overall Study NOT COMPLETED	15	17	26	21

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	R788 150 mg qd R788 150 mg, oral tablets, once daily, double-blind	R788 100 mg Bid R788 100 mg, oral tablets, twice daily, double-blind
Overall Study Lack of Efficacy	10	8	9	8
Overall Study Lost to Follow-up	1	2	2	2
Overall Study Withdrawal by Subject	2	2	3	2
Overall Study Physician Decision	0	0	1	2
Overall Study Severe Non-Compliance to Protocol	0	0	1	1
Overall Study Adverse Event	1	5	10	5
Overall Study Enrolled by mistake	0	0	0	1
Overall Study Due to exclusion criteria	1	0	0	0

Baseline Characteristics

Efficacy and Safety Study of R935788 Tablets to Treat Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo qd n=77 Participants Placebo to R788, oral tablets, once daily, double-blind	Placebo Bid n=76 Participants Placebo to R788, oral tablets, twice daily, double-blind	R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	R788 100 mg Bid n=152 Participants R788 100 mg, oral tablets, twice daily, double-blind	Total n=457 Participants Total of all reporting groups
Age, Continuous	51.3 Years STANDARD_DEVIATION 13.68 • n=5 Participants	53.4 Years STANDARD_DEVIATION 12.66 • n=7 Participants	52.6 Years STANDARD_DEVIATION 12.31 • n=5 Participants	52.5 Years STANDARD_DEVIATION 12.97 • n=4 Participants	52.5 Years STANDARD_DEVIATION 12.80 • n=21 Participants
Sex: Female, Male Female	67 Participants n=5 Participants	64 Participants n=7 Participants	128 Participants n=5 Participants	131 Participants n=4 Participants	390 Participants n=21 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants	21 Participants n=4 Participants	67 Participants n=21 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Intent-to-treat population includes all subjects that received study drug

The number of participants with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 6 months

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=153 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=151 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 20 (ACR20) Response at 6 Months	—	—	53 Participants	87 Participants	101 Participants

SECONDARY outcome

Timeframe: 1 week

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 1 week

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=153 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=151 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=146 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 20 (ACR20) Response at 1 Week	—	—	21 Participants	34 Participants	53 Participants

SECONDARY outcome

Timeframe: 2 weeks

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 2 weeks

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=153 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=148 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 20 (ACR20) Response at 2 Weeks	—	—	29 Participants	47 Participants	67 Participants

SECONDARY outcome

Timeframe: 1 month

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 1 month

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=151 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=150 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 20 (ACR20) Response at 1 Month	—	—	48 Participants	72 Participants	89 Participants

SECONDARY outcome

Timeframe: 6 weeks

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 6 weeks

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=148 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=151 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=150 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 20 (ACR20) Response at 6 Weeks	—	—	55 Participants	75 Participants	84 Participants

SECONDARY outcome

Timeframe: 2 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 2 months

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=151 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=151 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=149 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 20 (ACR20) Response at 2 Months	—	—	58 Participants	81 Participants	95 Participants

SECONDARY outcome

Timeframe: 3 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 3 months

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=152 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=150 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 20 (ACR20) Response at 3 Months	—	—	64 Participants	79 Participants	97 Participants

SECONDARY outcome

Timeframe: 4 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 4 months

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=152 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=151 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=147 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 20 (ACR20) Response at 4 Months	—	—	57 Participants	71 Participants	100 Participants

SECONDARY outcome

Timeframe: 5 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 5 months

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=151 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=150 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 20 (ACR20) Response at 5 Months	—	—	61 Participants	84 Participants	97 Participants

SECONDARY outcome

Timeframe: 1 week

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 50% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 1 week

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=153 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=151 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=146 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 50 (ACR50) Response at 1 Week	—	—	4 Participants	7 Participants	10 Participants

SECONDARY outcome

Timeframe: 2 weeks

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 50% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 2 weeks

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=153 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=148 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 50 (ACR50) Response at 2 Weeks	—	—	7 Participants	15 Participants	21 Participants

SECONDARY outcome

Timeframe: 1 month

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 50% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 1 month

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=151 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=150 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 50 (ACR50) Response at 1 Month	—	—	11 Participants	24 Participants	45 Participants

SECONDARY outcome

Timeframe: 6 weeks

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 50% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 6 weeks

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=148 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=151 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=150 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 50 (ACR50) Response at 6 Weeks	—	—	19 Participants	30 Participants	43 Participants

SECONDARY outcome

Timeframe: 2 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 50% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 2 months

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=151 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=151 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=149 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 50 (ACR50) Response at 2 Months	—	—	22 Participants	34 Participants	51 Participants

SECONDARY outcome

Timeframe: 3 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 50% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 3 months

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=152 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=150 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 50 (ACR50) Response at 3 Months	—	—	23 Participants	43 Participants	58 Participants

SECONDARY outcome

Timeframe: 4 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 50% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 4 months

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=152 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=151 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=147 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 50 (ACR50) Response at 4 Months	—	—	25 Participants	34 Participants	62 Participants

SECONDARY outcome

Timeframe: 5 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 50% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 5 months

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=151 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=150 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 50 (ACR50) Response at 5 Months	—	—	25 Participants	41 Participants	62 Participants

SECONDARY outcome

Timeframe: 6 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 50% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 6 months

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=153 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=151 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 50 (ACR50) Response at 6 Months	—	—	29 Participants	49 Participants	65 Participants

SECONDARY outcome

Timeframe: 1 week

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 70% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 1 week

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=153 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=151 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=146 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 70 (ACR70) Response at 1 Week	—	—	1 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 2 weeks

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 70% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 2 weeks

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=153 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=148 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 70 (ACR70) Response at 2 Weeks	—	—	1 Participants	5 Participants	7 Participants

SECONDARY outcome

Timeframe: 1 month

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 70% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 1 month

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=151 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=150 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 70 (ACR70) Response at 1 Month	—	—	7 Participants	13 Participants	14 Participants

SECONDARY outcome

Timeframe: 6 weeks

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 70% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 6 weeks

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=148 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=151 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=150 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 70 (ACR70) Response at 6 Weeks	—	—	5 Participants	13 Participants	16 Participants

SECONDARY outcome

Timeframe: 2 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 70% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 2 months

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=151 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=151 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=149 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 70 (ACR70) Response at 2 Months	—	—	4 Participants	15 Participants	20 Participants

SECONDARY outcome

Timeframe: 3 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 70% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 3 months

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=152 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=150 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 70 (ACR70) Response at 3 Months	—	—	10 Participants	19 Participants	30 Participants

SECONDARY outcome

Timeframe: 4 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 70% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 4 months

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=152 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=151 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=147 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 70 (ACR70) Response at 4 Months	—	—	8 Participants	17 Participants	32 Participants

SECONDARY outcome

Timeframe: 5 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 70% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 5 months

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=151 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=150 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 70 (ACR70) Response at 5 Months	—	—	8 Participants	20 Participants	33 Participants

SECONDARY outcome

Timeframe: 6 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with greater than or equal to 70% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 6 months

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=153 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=151 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology 70 (ACR70) Response at 6 Months	—	—	16 Participants	21 Participants	43 Participants

SECONDARY outcome

Timeframe: 1 week

Population: Intent-to-treat population with available data and received study drug.

The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA after 1 week of treatment

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=153 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=151 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=145 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology Index of Improvement (ACRn) at 1 Week	—	—	7.07 Score Standard Deviation 13.677	10.75 Score Standard Deviation 15.788	16.22 Score Standard Deviation 19.564

SECONDARY outcome

Timeframe: 2 weeks

Population: Intent-to-treat population with available data and received study drug.

The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA after 2 weeks of treatment

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=151 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=150 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=145 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology Index of Improvement (ACRn) at 2 Weeks	—	—	9.74 Score Standard Deviation 16.987	16.27 Score Standard Deviation 20.899	21.62 Score Standard Deviation 23.491

SECONDARY outcome

Timeframe: 1 month

Population: Intent-to-treat population with available data and received study drug.

The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA after 1 month of treatment

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=149 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=148 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=146 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology Index of Improvement (ACRn) at 1 Month	—	—	14.65 Score Standard Deviation 20.537	24.14 Score Standard Deviation 25.428	32.23 Score Standard Deviation 26.304

SECONDARY outcome

Timeframe: 6 weeks

Population: Intent-to-treat population with available data and received study drug.

The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA after 6 weeks of treatment

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=145 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=146 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=146 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology Index of Improvement (ACRn) at 6 Weeks	—	—	18.05 Score Standard Deviation 22.904	26.87 Score Standard Deviation 26.893	31.08 Score Standard Deviation 27.789

SECONDARY outcome

Timeframe: 2 months

Population: Intent-to-treat population with available data and received study drug.

The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA after 2 months of treatment

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=148 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=145 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=143 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology Index of Improvement (ACRn) at 2 Months	—	—	20.12 Score Standard Deviation 23.179	29.11 Score Standard Deviation 26.827	36.73 Score Standard Deviation 28.254

SECONDARY outcome

Timeframe: 3 months

Population: Intent-to-treat population with available data and received study drug.

The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA after 3 months of treatment

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=147 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=141 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=142 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology Index of Improvement (ACRn) at 3 Months	—	—	22.11 Score Standard Deviation 25.904	31.79 Score Standard Deviation 27.959	39.04 Score Standard Deviation 30.059

SECONDARY outcome

Timeframe: 4 months

Population: Intent-to-treat population with available data and received study drug.

The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA after 4 months of treatment

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=130 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=130 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=132 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology Index of Improvement (ACRn) at 4 Months	—	—	22.61 Score Standard Deviation 25.661	30.24 Score Standard Deviation 28.347	44.70 Score Standard Deviation 29.729

SECONDARY outcome

Timeframe: 5 months

Population: Intent-to-treat population with available data and received study drug.

The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA after 5 months of treatment

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=123 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=126 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=130 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology Index of Improvement (ACRn) at 5 Months	—	—	25.66 Score Standard Deviation 25.734	35.35 Score Standard Deviation 27.683	44.76 Score Standard Deviation 29.972

SECONDARY outcome

Timeframe: 6 months

Population: Intent-to-treat population with available data and received study drug.

The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA after 6 months of treatment

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=121 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=126 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=130 Participants R788 100 mg, oral tablets, twice daily, double-blind
American College of Rheumatology Index of Improvement (ACRn) at 6 Months	—	—	26.00 Score Standard Deviation 29.402	38.45 Score Standard Deviation 29.108	49.55 Score Standard Deviation 30.189

SECONDARY outcome

Timeframe: 1 month

Population: Intent-to-Treat Population with CRP as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=85 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=93 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=86 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 1 Month	—	—	2 Participants	10 Participants	4 Participants

SECONDARY outcome

Timeframe: 2 months

Population: Intent-to-Treat Population with CRP as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=83 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=94 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=82 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 2 Months	—	—	3 Participants	8 Participants	8 Participants

SECONDARY outcome

Timeframe: 3 months

Population: Intent-to-Treat Population with CRP as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=83 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=92 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=84 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 3 Months	—	—	5 Participants	7 Participants	11 Participants

SECONDARY outcome

Timeframe: 4 months

Population: Intent-to-Treat Population with CRP as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=73 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=84 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=80 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 4 Months	—	—	4 Participants	10 Participants	15 Participants

SECONDARY outcome

Timeframe: 5 months

Population: Intent-to-Treat Population with CRP as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=71 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=81 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=76 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 5 Months	—	—	5 Participants	8 Participants	24 Participants

SECONDARY outcome

Timeframe: 6 months

Population: Intent-to-Treat Population with CRP as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=70 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=81 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=77 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 6 Months	—	—	6 Participants	17 Participants	20 Participants

SECONDARY outcome

Timeframe: 1 month

Population: Intent-to-Treat Population with CRP as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=85 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=93 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=86 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 1 Month	—	—	6 Participants	15 Participants	15 Participants

SECONDARY outcome

Timeframe: 2 months

Population: Intent-to-Treat Population with CRP as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=83 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=94 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=82 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 2 Months	—	—	9 Participants	19 Participants	21 Participants

SECONDARY outcome

Timeframe: 3 months

Population: Intent-to-Treat Population with CRP as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=83 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=92 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=84 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 3 Months	—	—	8 Participants	25 Participants	21 Participants

SECONDARY outcome

Timeframe: 4 months

Population: Intent-to-Treat Population with CRP as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=73 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=84 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=80 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 4 Months	—	—	9 Participants	20 Participants	28 Participants

SECONDARY outcome

Timeframe: 5 months

Population: Intent-to-Treat Population with CRP as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=71 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=81 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=76 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 5 Months	—	—	8 Participants	21 Participants	34 Participants

SECONDARY outcome

Timeframe: 6 months

Population: Intent-to-Treat Population with CRP as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=70 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=81 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=77 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 6 Months	—	—	7 Participants	26 Participants	30 Participants

SECONDARY outcome

Timeframe: 1 month

Population: Intent-to-Treat Population with ESR as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=64 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=53 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=61 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 1 Month	—	—	2 Participants	3 Participants	12 Participants

SECONDARY outcome

Timeframe: 2 months

Population: Intent-to-Treat Population with ESR as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=64 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=50 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=60 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 2 Months	—	—	4 Participants	4 Participants	13 Participants

SECONDARY outcome

Timeframe: 3 months

Population: Intent-to-Treat Population with ESR as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=64 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=49 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=58 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 3 Months	—	—	4 Participants	3 Participants	19 Participants

SECONDARY outcome

Timeframe: 4 months

Population: Intent-to-Treat Population with ESR as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=57 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=46 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=53 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 4 Months	—	—	5 Participants	3 Participants	15 Participants

SECONDARY outcome

Timeframe: 5 months

Population: Intent-to-Treat Population with ESR as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=52 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=45 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=54 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 5 Months	—	—	3 Participants	7 Participants	12 Participants

SECONDARY outcome

Timeframe: 6 months

Population: Intent-to-Treat Population with ESR as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=51 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=44 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=54 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 6 Months	—	—	3 Participants	9 Participants	21 Participants

SECONDARY outcome

Timeframe: 1 month

Population: Intent-to-Treat Population with ESR as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=64 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=53 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=61 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 1 Month	—	—	3 Participants	6 Participants	18 Participants

SECONDARY outcome

Timeframe: 2 months

Population: Intent-to-Treat Population with ESR as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=64 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=50 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=60 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 2 Months	—	—	9 Participants	7 Participants	23 Participants

SECONDARY outcome

Timeframe: 3 months

Population: Intent-to-Treat Population with ESR as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=64 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=49 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=58 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 3 Months	—	—	7 Participants	8 Participants	22 Participants

SECONDARY outcome

Timeframe: 4 months

Population: Intent-to-Treat Population with ESR as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=57 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=46 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=53 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 4 Months	—	—	8 Participants	6 Participants	23 Participants

SECONDARY outcome

Timeframe: 5 months

Population: Intent-to-Treat Population with ESR as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=52 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=45 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=54 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 5 Months	—	—	7 Participants	8 Participants	24 Participants

SECONDARY outcome

Timeframe: 6 months

Population: Intent-to-Treat Population with ESR as Primary Phase Reactant with available data and received study drug.

Number of participants with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=51 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=44 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=54 Participants R788 100 mg, oral tablets, twice daily, double-blind
Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 6 Months	—	—	8 Participants	11 Participants	29 Participants

SECONDARY outcome

Timeframe: Baseline to 6 months

Population: Intent-to-treat population with available data and received study drug.

Change from baseline in FACIT-F, which is a patient-reported 13-item questionnaire that assesses fatigue, calculated as the score at 6 months minus the score at baseline. The FACIT-F runs from 0 to 52 with lower scores indicating higher fatigue. A positive change from baseline indicates an improvement in fatigue after treatment.

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=109 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=107 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=117 Participants R788 100 mg, oral tablets, twice daily, double-blind
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at 6 Months	—	—	4.5 Score Standard Deviation 9.79	5.7 Score Standard Deviation 10.28	7.4 Score Standard Deviation 10.87

SECONDARY outcome

Timeframe: Baseline to 6 months

Population: Intent-to-treat population with available data and received study drug.

Change from baseline in the PCS of the SF-36 (which assesses health and wellbeing), calculated as the score at 6 months minus the score at baseline. The PCS ranges from 0 to 100 with 100 indicating the highest level of functioning possible. A positive change indicates an improvement in PCS after treatment

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=118 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=124 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=129 Participants R788 100 mg, oral tablets, twice daily, double-blind
Short Form Health Survey (SF-36) Physical Component Summary (PCS) at 6 Months	—	—	4.902 Score Standard Deviation 8.4808	5.903 Score Standard Deviation 8.9541	8.524 Score Standard Deviation 8.7068

SECONDARY outcome

Timeframe: Baseline to 6 months

Population: Intent-to-treat population with available data and received study drug.

Change from baseline in the MCS of the SF-36 (which assesses health and wellbeing), calculated as the score at 6 months minus the score at baseline. The MCS ranges from 0 to 100 with 100 indicating the highest level of functioning possible. A positive change indicates an improvement in MCS after treatment

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled n=118 Participants Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=125 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=129 Participants R788 100 mg, oral tablets, twice daily, double-blind
Short Form Health Survey (SF-36) Mental Component Summary (MCS) at 6 Months	—	—	3.711 Score Standard Deviation 10.7098	2.033 Score Standard Deviation 10.7089	3.990 Score Standard Deviation 10.5129

SECONDARY outcome

Timeframe: Any time between baseline and 6 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with ALT (a test of liver function) values greater than 1.5 times the ULN

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd n=77 Participants Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid n=76 Participants Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=152 Participants R788 100 mg, oral tablets, twice daily, double-blind
Alanine Aminotransferase (ALT) >1.5x Upper Limit of Normal (ULN)	3 Participants	11 Participants	—	28 Participants	31 Participants

SECONDARY outcome

Timeframe: Any time between baseline and 6 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with ALT (a test of liver function) values greater than 1.5 to 2 times the ULN

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd n=77 Participants Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid n=76 Participants Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=152 Participants R788 100 mg, oral tablets, twice daily, double-blind
Alanine Aminotransferase (ALT) >1.5-2x Upper Limit of Normal (ULN)	1 Participants	5 Participants	—	14 Participants	15 Participants

SECONDARY outcome

Timeframe: Any time between baseline and 6 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with ALT (a test of liver function) values greater than 2 to 3 times the ULN

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd n=77 Participants Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid n=76 Participants Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=152 Participants R788 100 mg, oral tablets, twice daily, double-blind
Alanine Aminotransferase (ALT) >2-3x Upper Limit of Normal (ULN)	1 Participants	4 Participants	—	8 Participants	10 Participants

SECONDARY outcome

Timeframe: Any time between baseline and 6 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with ALT (a test of liver function) values greater than 3 times the ULN

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd n=77 Participants Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid n=76 Participants Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=152 Participants R788 100 mg, oral tablets, twice daily, double-blind
Alanine Aminotransferase (ALT) >3x Upper Limit of Normal (ULN)	1 Participants	2 Participants	—	6 Participants	6 Participants

SECONDARY outcome

Timeframe: Any time between baseline and 6 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with ALT (a test of liver function) values greater than 3 to 5 times the ULN

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd n=77 Participants Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid n=76 Participants Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=152 Participants R788 100 mg, oral tablets, twice daily, double-blind
Alanine Aminotransferase (ALT) >3-5x Upper Limit of Normal (ULN)	1 Participants	1 Participants	—	3 Participants	3 Participants

SECONDARY outcome

Timeframe: Any time between baseline and 6 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with ALT (a test of liver function) values greater than 5 to 10 times the ULN

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd n=77 Participants Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid n=76 Participants Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=152 Participants R788 100 mg, oral tablets, twice daily, double-blind
Alanine Aminotransferase (ALT) >5-10x Upper Limit of Normal (ULN)	0 Participants	1 Participants	—	3 Participants	3 Participants

SECONDARY outcome

Timeframe: Any time between baseline and 6 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with ALT (a test of liver function) values greater than 10 times the ULN

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd n=77 Participants Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid n=76 Participants Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=152 Participants R788 100 mg, oral tablets, twice daily, double-blind
Alanine Aminotransferase (ALT) >10x Upper Limit of Normal (ULN)	0 Participants	0 Participants	—	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Any time between baseline and 6 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with AST (a test of liver function) values greater than 1.5 times the ULN

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd n=77 Participants Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid n=76 Participants Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=152 Participants R788 100 mg, oral tablets, twice daily, double-blind
Aspartate Aminotransferase (AST) >1.5x Upper Limit of Normal (ULN)	1 Participants	4 Participants	—	19 Participants	11 Participants

SECONDARY outcome

Timeframe: Any time between baseline and 6 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with AST (a test of liver function) values greater than 1.5-2 times the ULN

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd n=77 Participants Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid n=76 Participants Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=152 Participants R788 100 mg, oral tablets, twice daily, double-blind
Aspartate Aminotransferase (AST) >1.5-2x Upper Limit of Normal (ULN)	0 Participants	1 Participants	—	13 Participants	5 Participants

SECONDARY outcome

Timeframe: Any time between baseline and 6 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with AST (a test of liver function) values greater than 2 to 3 times the ULN

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd n=77 Participants Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid n=76 Participants Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=152 Participants R788 100 mg, oral tablets, twice daily, double-blind
Aspartate Aminotransferase (AST) >2-3x Upper Limit of Normal (ULN)	0 Participants	2 Participants	—	4 Participants	1 Participants

SECONDARY outcome

Timeframe: Any time between baseline and 6 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with AST (a test of liver function) values greater than 3 times the ULN

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd n=77 Participants Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid n=76 Participants Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=152 Participants R788 100 mg, oral tablets, twice daily, double-blind
Aspartate Aminotransferase (AST) >3x Upper Limit of Normal (ULN)	1 Participants	1 Participants	—	2 Participants	5 Participants

SECONDARY outcome

Timeframe: Any time between baseline and 6 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with AST (a test of liver function) values greater than 3 to 5 times the ULN

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd n=77 Participants Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid n=76 Participants Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=152 Participants R788 100 mg, oral tablets, twice daily, double-blind
Aspartate Aminotransferase (AST) >3-5x Upper Limit of Normal (ULN)	0 Participants	1 Participants	—	2 Participants	5 Participants

SECONDARY outcome

Timeframe: Any time between baseline and 6 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with AST (a test of liver function) values greater than 5 to 10 times the ULN

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd n=77 Participants Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid n=76 Participants Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=152 Participants R788 100 mg, oral tablets, twice daily, double-blind
Aspartate Aminotransferase (AST) >5-10 x Upper Limit of Normal (ULN)	1 Participants	0 Participants	—	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Any time between baseline and 6 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with AST (a test of liver function) values greater than 10 times the ULN

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd n=77 Participants Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid n=76 Participants Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=152 Participants R788 100 mg, oral tablets, twice daily, double-blind
Aspartate Aminotransferase (AST) >10 x Upper Limit of Normal (ULN)	0 Participants	0 Participants	—	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Any time between baseline and 6 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with alkaline phosphatase (a test of liver function) values greater than 1.5 times the ULN and greater than 1.5 times baseline

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd n=77 Participants Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid n=76 Participants Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=152 Participants R788 100 mg, oral tablets, twice daily, double-blind
Alkaline Phosphatase >1.5 x Upper Limit of Normal (ULN) and >1.5 Times Baseline	0 Participants	1 Participants	—	1 Participants	6 Participants

SECONDARY outcome

Timeframe: Any time between baseline and 6 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with bilirubin (a test of liver function) values greater than 1.5 times the ULN

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd n=77 Participants Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid n=76 Participants Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=152 Participants R788 100 mg, oral tablets, twice daily, double-blind
Bilirubin >1.5 x Upper Limit of Normal (ULN)	0 Participants	2 Participants	—	4 Participants	4 Participants

SECONDARY outcome

Timeframe: Any time between baseline and 6 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with bilirubin (a test of liver function) values greater than 2 times the ULN

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd n=77 Participants Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid n=76 Participants Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=152 Participants R788 100 mg, oral tablets, twice daily, double-blind
Bilirubin >2 x Upper Limit of Normal (ULN)	0 Participants	0 Participants	—	0 Participants	3 Participants

SECONDARY outcome

Timeframe: Any time between baseline and 6 months

Population: Intent-to-treat population with available data and received study drug.

The number of participants with ANC (a test of liver function) values lower than 1500/mm3

Outcome measures

Outcome measures
Measure	Arm 1 - Placebo qd n=77 Participants Placebo to R788, oral tablets, once daily, double-blind	Arm 2 - Placebo Bid n=76 Participants Placebo to R788, oral tablets, twice daily, double-blind	Arm 3 - Placebo Pooled Placebo to R788, oral tablets once and twice daily pooled	Arm 4 - R788 150 mg qd n=152 Participants R788 150 mg, oral tablets, once daily, double-blind	Arm 5 - R788 100 mg Bid n=152 Participants R788 100 mg, oral tablets, twice daily, double-blind
Absolute Neutrophil Count (ANC) <1500/mm3	1 Participants	0 Participants	—	10 Participants	9 Participants

Adverse Events

Placebo qd

Serious events: 2 serious events

Other events: 26 other events

Deaths: 0 deaths

Placebo Bid

Serious events: 4 serious events

Other events: 20 other events

Deaths: 0 deaths

R788 150 mg qd

Serious events: 5 serious events

Other events: 62 other events

Deaths: 0 deaths

R788 100 mg Bid

Serious events: 1 serious events

Other events: 73 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo qd n=77 participants at risk Placebo to R788, oral tablets, once daily, double-blind	Placebo Bid n=76 participants at risk Placebo to R788, oral tablets, twice daily, double-blind	R788 150 mg qd n=152 participants at risk R788 150 mg, oral tablets, once daily, double-blind	R788 100 mg Bid n=152 participants at risk R788 100 mg, oral tablets, twice daily, double-blind
Gastrointestinal disorders DIARRHOEA	5.2% 4/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	1.3% 1/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	11.8% 18/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	19.1% 29/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Gastrointestinal disorders NAUSEA	1.3% 1/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	7.9% 6/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	5.9% 9/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	4.6% 7/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	3.9% 3/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	2.6% 2/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	2.0% 3/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	6.6% 10/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Infections and infestations URINARY TRACT INFECTION	2.6% 2/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	6.6% 5/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	3.3% 5/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	5.9% 9/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Infections and infestations INFLUENZA	2.6% 2/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	5.3% 4/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	2.0% 3/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	3.3% 5/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Investigations TRANSAMINASES INCREASED	3.9% 3/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	2.6% 2/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	4.6% 7/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	5.3% 8/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Metabolism and nutrition disorders DYSLIPIDAEMIA	3.9% 3/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	2.6% 2/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	5.3% 8/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	3.3% 5/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Musculoskeletal and connective tissue disorders BACK PAIN	5.2% 4/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	1.3% 1/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.66% 1/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.66% 1/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Nervous system disorders HEADACHE	3.9% 3/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	6.6% 5/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	6.6% 10/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	5.9% 9/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Skin and subcutaneous tissue disorders RASH	6.5% 5/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	1.3% 2/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	2.0% 3/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Vascular disorders HYPERTENSION	5.2% 4/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	3.9% 3/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	11.8% 18/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	13.8% 21/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses

Additional Information

Anne-Marie Duliege, MD

Rigel

Phone: 650-624-1100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Placebo qd n=77 participants at risk Placebo to R788, oral tablets, once daily, double-blind	Placebo Bid n=76 participants at risk Placebo to R788, oral tablets, twice daily, double-blind	R788 150 mg qd n=152 participants at risk R788 150 mg, oral tablets, once daily, double-blind	R788 100 mg Bid n=152 participants at risk R788 100 mg, oral tablets, twice daily, double-blind
Cardiac disorders ANGINA UNSTABLE	1.3% 1/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.66% 1/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Gastrointestinal disorders DUODENAL ULCER	0.00% 0/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.66% 1/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Gastrointestinal disorders GASTROINTESTINAL HAEMORRHAGE	0.00% 0/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.66% 1/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Gastrointestinal disorders PANCREATITIS	0.00% 0/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.66% 1/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Gastrointestinal disorders VOMITING	0.00% 0/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.66% 1/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Infections and infestations ARTHRITIS INFECTIVE	0.00% 0/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	1.3% 1/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Infections and infestations BURSITIS INFECTIVE	1.3% 1/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Infections and infestations CELLULITIS	0.00% 0/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	1.3% 1/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.66% 1/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Infections and infestations ERYSIPELAS	0.00% 0/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.66% 1/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Infections and infestations GALLBLADDER EMPYEMA	0.00% 0/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.66% 1/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Infections and infestations HERPES ZOSTER OPHTHALMIC	0.00% 0/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.66% 1/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Infections and infestations OSTEOMYELITIS	0.00% 0/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.66% 1/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Infections and infestations PYELONEPHRITIS	0.00% 0/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.66% 1/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Infections and infestations SOFT TISSUE INFECTION	0.00% 0/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	1.3% 1/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Infections and infestations URINARY TRACT INFECTION	0.00% 0/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.66% 1/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Injury, poisoning and procedural complications SUBDURAL HAEMATOMA	0.00% 0/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.66% 1/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Musculoskeletal and connective tissue disorders ARTHRITIS	0.00% 0/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	1.3% 1/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Neoplasms benign, malignant and unspecified (incl cysts and polyps) CARCINOMA IN SITU OF PENIS	0.00% 0/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.66% 1/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Neoplasms benign, malignant and unspecified (incl cysts and polyps) RENAL CELL CARCINOMA STAGE UNSPECIFIED	0.00% 0/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.66% 1/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Neoplasms benign, malignant and unspecified (incl cysts and polyps) SQUAMOUS CELL CARCINOMA	0.00% 0/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.66% 1/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Nervous system disorders TRANSIENT ISCHAEMIC ATTACK	0.00% 0/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	1.3% 1/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Pregnancy, puerperium and perinatal conditions STILLBIRTH	0.00% 0/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.66% 1/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Renal and urinary disorders HYDRONEPHROSIS	0.00% 0/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.66% 1/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
Respiratory, thoracic and mediastinal disorders ASTHMATIC CRISIS	0.00% 0/77 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/76 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.00% 0/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses	0.66% 1/152 Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses