Trial Outcomes & Findings for Effects of Tofacitinib (CP-690,550) on Magnetic Resonance Imaging (MRI)- Assessed Joint Structure In Early Rheumatoid Arthritis (RA) (NCT NCT01164579)

NCT ID: NCT01164579

Last Updated: 2015-04-22

Results Overview

Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the first through fifth MCP joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 24. A negative value in synovitis change from Baseline score indicates an improvement.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 109 participants
• Primary outcome timeframe: Month 3
• Results posted on: 2015-04-22

Participant Flow

Participant milestones

Measure	Tofacitinib (CP-690,550) Plus Methotrexate (MTX) Participants received CP-690,550 10 milligrams (mg), tablets, orally (PO), twice daily (BID), and MTX 10 mg per week (mg/week) to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Overall Study STARTED	36	36	37
Overall Study COMPLETED	28	27	21
Overall Study NOT COMPLETED	8	9	16

Reasons for withdrawal

Measure	Tofacitinib (CP-690,550) Plus Methotrexate (MTX) Participants received CP-690,550 10 milligrams (mg), tablets, orally (PO), twice daily (BID), and MTX 10 mg per week (mg/week) to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Overall Study Lack of Efficacy	0	0	6
Overall Study Lost to Follow-up	1	1	0
Overall Study Withdrawal by Subject	2	5	3
Overall Study Protocol Violation	0	1	2
Overall Study Adverse Event	4	2	5
Overall Study Reason not specified	1	0	0

Baseline Characteristics

Effects of Tofacitinib (CP-690,550) on Magnetic Resonance Imaging (MRI)- Assessed Joint Structure In Early Rheumatoid Arthritis (RA)

Baseline characteristics by cohort

Measure	Tofacitinib (CP-690,550) Plus MTX n=36 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=36 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=37 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Total n=109 Participants Total of all reporting groups
Age, Continuous	47.8 years STANDARD_DEVIATION 12.3 • n=5 Participants	50.8 years STANDARD_DEVIATION 12.8 • n=7 Participants	47.8 years STANDARD_DEVIATION 11.6 • n=5 Participants	48.8 years STANDARD_DEVIATION 12.2 • n=4 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	30 Participants n=7 Participants	29 Participants n=5 Participants	90 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants	19 Participants n=4 Participants

PRIMARY outcome

Timeframe: Month 3

Population: Evaluable Set: all randomized participants who received at least 1 dose of the randomized investigational drug and for whom a variable is nonmissing at both baseline and the specified timepoint.

Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the first through fifth MCP joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 24. A negative value in synovitis change from Baseline score indicates an improvement.

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=30 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=32 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=31 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Change From Baseline to Month 3 in Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) Wrist and Metacarpophalangeal (MCP) Synovitis	-0.80 score on a scale Standard Error 0.41	-0.69 score on a scale Standard Error 0.40	-0.17 score on a scale Standard Error 0.40

PRIMARY outcome

Timeframe: Month 6

Population: Evaluable Set

Bone edema was assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Bone edema was defined as a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Each bone was scored separately; the scale was 0-3 based on the proportion of bone with edema, as follows 0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. OMERACT RAMRIS total bone edema score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist was 75 (range 0-75). Increasing score=greater severity.

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=33 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=29 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=28 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Change From Baseline to Month 6 in OMERACT RAMRIS Wrist and MCP Bone Marrow Edema	-1.26 score on a scale Standard Error 0.41	-1.45 score on a scale Standard Error 0.42	0.29 score on a scale Standard Error 0.42

SECONDARY outcome

Timeframe: Months 1, 6, and 12

Population: Evaluable Set

Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the first through fifth MCP joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 24. A negative value in synovitis change from Baseline score indicates an improvement.

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=33 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=31 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=35 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis Month 1 (n=28,31,35)	-0.42 score on a scale Standard Error 0.42	-0.34 score on a scale Standard Error 0.40	-0.17 score on a scale Standard Error 0.38
Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis Month 6 (n=33,29,28)	-1.22 score on a scale Standard Error 0.40	-1.29 score on a scale Standard Error 0.41	-0.28 score on a scale Standard Error 0.42
Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis Month 12 (n=29,26,21)	-2.26 score on a scale Standard Error 0.41	-1.16 score on a scale Standard Error 0.43	-0.66 score on a scale Standard Error 0.46

SECONDARY outcome

Timeframe: Months 1, 3, and 12

Population: Evaluable Set; n=number of participants assessed for the specified parameter at a given visit.

Bone edema was assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Bone edema was defined as a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Each bone was scored separately; the scale was 0â€"3 based on the proportion of bone with edema, as follows 0: no edema; 1: 1â€"33% of bone edematous; 2: 34â€"66% of bone edematous; 3: 67â€"100%. OMERACT RAMRIS total bone edema score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist was 75 (range 0-75). Increasing score=greater severity.

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=30 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=32 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=35 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP Month 1 (n=28,31,35)	-0.29 score on a scale Standard Error 0.43	0.19 score on a scale Standard Error 0.41	0.11 score on a scale Standard Error 0.39
Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP Month 3 (n=30,32,31)	-0.77 score on a scale Standard Error 0.42	-0.86 score on a scale Standard Error 0.41	0.47 score on a scale Standard Error 0.41
Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP Month 12 (n=29,26,21)	-1.52 score on a scale Standard Error 0.42	-1.70 score on a scale Standard Error 0.43	0.59 score on a scale Standard Error 0.46

SECONDARY outcome

Timeframe: Months 1, 3, 6, and 12

Population: Evaluable Set

Bone erosion assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Each site was scored in 1.0 increments from 0 (no damage) to 10 (severe damage), indicating erosion (each unit=10% bone loss) of original articular bone. OMERACT RAMRIS total erosion score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist is 250 (range 0-250). Increasing score=greater severity.

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=33 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=32 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=35 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions Month 1 (n=28,31,35)	-0.12 score on a scale Standard Error 0.25	0.27 score on a scale Standard Error 0.25	0.27 score on a scale Standard Error 0.24
Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions Month 3 (n=30,32,31)	-0.12 score on a scale Standard Error 0.25	0.36 score on a scale Standard Error 0.24	0.44 score on a scale Standard Error 0.25
Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions Month 6 (n=33,29,28)	-0.06 score on a scale Standard Error 0.25	-0.02 score on a scale Standard Error 0.25	0.65 score on a scale Standard Error 0.25
Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions Month 12 (n=29,26,21)	-0.11 score on a scale Standard Error 0.25	-0.08 score on a scale Standard Error 0.25	1.18 score on a scale Standard Error 0.26

SECONDARY outcome

Timeframe: Months 6 and 12

Population: Evaluable Set; n=number of participants assessed for the specified parameter at a given visit.

Modified TSS is a measure of change in joint health. TSS is defined as joint space narrowing score (range 0 [no narrowing] to 168 [high narrowing]) plus (+) erosion score (range is from 0 [no erosion] to 280 [high erosion]). The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=34 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=36 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=37 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Modified Total Sharp Score (mTSS) at Months 6 and 12 Month 6 (n=29,27,28)	11.28 score on a scale Standard Error 0.50	10.70 score on a scale Standard Error 0.51	11.77 score on a scale Standard Error 0.52
Modified Total Sharp Score (mTSS) at Months 6 and 12 Month 12 (n=26,25,22)	11.70 score on a scale Standard Error 0.51	10.69 score on a scale Standard Error 0.52	12.21 score on a scale Standard Error 0.54

SECONDARY outcome

Timeframe: Months 6 and 12

Population: Evaluable Set; n=number of participants assessed for the specified parameter at a given visit.

Modified TSS is a measure of change in joint health. TSS is defined as joint space narrowing score (range 0 [no narrowing] to 168 [high narrowing]) + erosion score (range is from 0 [no erosion] to 280 [high erosion]). The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=29 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=27 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=28 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Change From Baseline to Months 6 and 12 in mTSS Month 6 (n=29,27,28)	0.44 scores on a scale Standard Error 0.50	-0.14 scores on a scale Standard Error 0.51	0.93 scores on a scale Standard Error 0.52
Change From Baseline to Months 6 and 12 in mTSS Month 12 (n=26,25,22)	0.85 scores on a scale Standard Error 0.51	-0.15 scores on a scale Standard Error 0.52	1.36 scores on a scale Standard Error 0.54

SECONDARY outcome

Timeframe: Months 6 and 12

Population: Evaluable Set; n=number of participants assessed for the specified parameter at a given visit.

JSN score (a component of the modified TSS) is a measure of change in joint health. JSN score range is 0 (no narrowing) to 168 (high narrowing). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=29 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=27 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=28 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Joint Space Narrowing (JSN) Scores at Months 6 and 12 Month 6 (n=29,27,28)	5.45 score on a scale Standard Error 0.34	5.11 score on a scale Standard Error 0.35	5.52 score on a scale Standard Error 0.36
Joint Space Narrowing (JSN) Scores at Months 6 and 12 Month 12 (n=26,25,22)	5.59 score on a scale Standard Error 0.35	5.05 score on a scale Standard Error 0.36	5.88 score on a scale Standard Error 0.37

SECONDARY outcome

Timeframe: Months 6 and 12

Population: Evaluable Set; n=number of participants assessed for the specified parameter at a given visit.

JSN score (a component of the modified TSS) is a measure of change in joint health. JSN score range is 0 (no narrowing) to 168 (high narrowing). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=29 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=27 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=28 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Change From Baseline to Months 6 and 12 in JSN Scores Month 6 (n=29,27,28)	0.29 scores on a scale Standard Error 0.34	-0.06 scores on a scale Standard Error 0.35	0.35 scores on a scale Standard Error 0.36
Change From Baseline to Months 6 and 12 in JSN Scores Month 12 (n=26,25,22)	0.43 scores on a scale Standard Error 0.35	-0.12 scores on a scale Standard Error 0.36	0.71 scores on a scale Standard Error 0.37

SECONDARY outcome

Timeframe: Months 6 and 12

Population: Evaluable Set; n=number of participants assessed for the specified parameter at a given visit.

Erosion score (a component of the modified TSS) is a measure of change in joint health. Erosion score range is from 0 (no erosion) to 280 (high erosion). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=29 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=27 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=28 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Erosion Scores at Months 6 and 12 Month 6 (n=29,27,28)	5.84 scores on a scale Standard Error 0.24	5.59 scores on a scale Standard Error 0.25	6.26 scores on a scale Standard Error 0.25
Erosion Scores at Months 6 and 12 Month 12 (n=26,25,22)	6.10 scores on a scale Standard Error 0.25	5.64 scores on a scale Standard Error 0.26	6.33 scores on a scale Standard Error 0.27

SECONDARY outcome

Timeframe: Months 6 and 12

Population: Evaluable Set; n=number of participants assessed for the specified parameter at a given visit.

Erosion score (a component of the modified TSS) is a measure of change in joint health. Erosion score range is from 0 (no erosion) to 280 (high erosion). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=29 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=27 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=28 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Change From Baseline to Months 6 and 12 in Erosion Score Month 6 (n=29,27,28)	0.16 scores on a scale Standard Error 0.24	-0.10 scores on a scale Standard Error 0.25	0.58 scores on a scale Standard Error 0.25
Change From Baseline to Months 6 and 12 in Erosion Score Month 12 (n=26,25,22)	0.42 scores on a scale Standard Error 0.25	-0.05 scores on a scale Standard Error 0.26	0.65 scores on a scale Standard Error 0.27

SECONDARY outcome

Timeframe: Months 1, 2, 3, 6, 9, and 12

Population: FAS Non-Responder Imputation (NRI) method: participants with missing values were considered to be non-responders. n=number of participants assessed for the specified parameter at a given visit.

ACR20 response: greater than or equal to (≥)20% improvement in tender joint count; ≥20% improvement in swollen joint count; and ≥20% improvement in at least 3 of 5 remaining ACR core measures: Participant's Assessment of Pain; Participant's Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP).

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=35 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=36 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=37 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response Month 1 (n=35,35,37)	42.86 percentage of participants	57.14 percentage of participants	29.73 percentage of participants
Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response Month 2 (n=35,36,37)	68.57 percentage of participants	61.11 percentage of participants	40.54 percentage of participants
Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response Month 3 (n=35,36,37)	77.14 percentage of participants	61.11 percentage of participants	48.65 percentage of participants
Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response Month 6 (n=35,36,37)	74.29 percentage of participants	66.67 percentage of participants	45.95 percentage of participants
Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response Month 9 (n=35,36,37)	71.43 percentage of participants	58.33 percentage of participants	43.24 percentage of participants
Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response Month 12 (n=35,36,37)	71.43 percentage of participants	61.11 percentage of participants	43.24 percentage of participants

SECONDARY outcome

Timeframe: Months 1, 2, 3, 6, 9, and 12

Population: FAS NRI; n=number of participants assess for the specified parameter at a given visit.

ACR50 response: ≥ 50% improvement in tender or swollen joint counts and 50% improvement in 3 of the following 5 criteria: 1) Physician's Global Assessment of Disease Activity, 2) Participant's Assessment of disease activity, 3) Paricipant's Assessment of Pain, 4) Participant's assessment of functional disability via a HAQ, and 5) CRP at each visit.

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=35 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=36 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=37 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Percentage of Participants With an ACR 50% Improvement (ACR50) Response Month 1 (n=35,35,37)	22.86 percentage of participants	22.86 percentage of participants	2.70 percentage of participants
Percentage of Participants With an ACR 50% Improvement (ACR50) Response Month 2 (n=35,36,37)	45.71 percentage of participants	33.33 percentage of participants	16.22 percentage of participants
Percentage of Participants With an ACR 50% Improvement (ACR50) Response Month 3 (n=35,36,37)	48.57 percentage of participants	50.00 percentage of participants	24.32 percentage of participants
Percentage of Participants With an ACR 50% Improvement (ACR50) Response Month 6 (n=35,36,37)	57.14 percentage of participants	47.22 percentage of participants	21.62 percentage of participants
Percentage of Participants With an ACR 50% Improvement (ACR50) Response Month 9 (n=35,36,37)	57.14 percentage of participants	44.44 percentage of participants	29.73 percentage of participants
Percentage of Participants With an ACR 50% Improvement (ACR50) Response Month 12 (n=35,36,37)	57.14 percentage of participants	44.44 percentage of participants	29.73 percentage of participants

SECONDARY outcome

Timeframe: Months 1, 2, 3, 6, 9, and 12

Population: FAS NRI; n=number of participants assessed for the specified parameter at a given visit.

ACR70 response: ≥70% improvement in tender or swollen joint counts and 70% improvement in 3 of the following 5 criteria: 1) Physician's Global Assessment of Disease Activity, 2) Participant's Assessment of Disease Activity, 3) Participant's Assessment of Pain, 4) Participant's Assessment of Functional Disability via a HAQ, and 5) CRP at each visit.

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=35 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=36 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=37 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Percentage of Participants With an ACR 70% Improvement (ACR70) Response Month 1 (n=35,35,37)	8.57 percentage of participants	2.86 percentage of participants	0.00 percentage of participants
Percentage of Participants With an ACR 70% Improvement (ACR70) Response Month 2 (n=35,36,37)	31.43 percentage of participants	22.22 percentage of participants	5.41 percentage of participants
Percentage of Participants With an ACR 70% Improvement (ACR70) Response Month 3 (n=35,36,37)	25.71 percentage of participants	27.78 percentage of participants	10.81 percentage of participants
Percentage of Participants With an ACR 70% Improvement (ACR70) Response Month 6 (n=35,36,37)	34.29 percentage of participants	30.56 percentage of participants	21.62 percentage of participants
Percentage of Participants With an ACR 70% Improvement (ACR70) Response Month 9 (n=35,36,37)	31.43 percentage of participants	33.33 percentage of participants	18.92 percentage of participants
Percentage of Participants With an ACR 70% Improvement (ACR70) Response Month 12 (n=35,36,37)	22.86 percentage of participants	33.33 percentage of participants	21.62 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Months 1, 2, 3, 6, 9, and 12

Population: FAS; n=number of participants assess for the specified parameter at a given visit.

DAS28-3 (CRP) was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) less than or equal to (≤)3.2 implied low disease activity and greater than (>)3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) less than (<)2.6 = remission.

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=36 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=36 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=37 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) Baseline (n=36,36,37)	5.14 score on a scale Standard Deviation 0.96	5.48 score on a scale Standard Deviation 0.78	5.36 score on a scale Standard Deviation 0.80
Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) Month 1 (n=33,35,37)	3.71 score on a scale Standard Deviation 1.15	4.03 score on a scale Standard Deviation 0.91	4.65 score on a scale Standard Deviation 1.07
Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) Month 2 (n=33,33,32)	2.99 score on a scale Standard Deviation 1.17	3.52 score on a scale Standard Deviation 1.15	4.21 score on a scale Standard Deviation 1.31
Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) Month 3 (n=33,33,31)	3.06 score on a scale Standard Deviation 1.02	3.46 score on a scale Standard Deviation 1.09	3.87 score on a scale Standard Deviation 1.43
Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) Month 6 (n=31,29,29)	2.74 score on a scale Standard Deviation 1.15	2.75 score on a scale Standard Deviation 0.95	3.92 score on a scale Standard Deviation 1.49
Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) Month 9 (n=30,28,24)	2.37 score on a scale Standard Deviation 0.98	2.85 score on a scale Standard Deviation 0.90	3.58 score on a scale Standard Deviation 1.63
Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) Month 12 (n=27,26,20)	2.49 score on a scale Standard Deviation 1.02	2.68 score on a scale Standard Deviation 1.05	3.58 score on a scale Standard Deviation 1.40

SECONDARY outcome

Timeframe: Months 1, 2, 3, 6, 9, and 12

Population: FAS; n=number of participants assessed for the specified parameter at a given visit.

DAS28-3 (CRP) was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity.

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=33 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=35 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=37 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Change From Baseline in DAS28-3 (CRP) Month 12 (n=27,26,20)	-2.78 scores on a scale Standard Error 0.20	-2.61 scores on a scale Standard Error 0.20	-1.77 scores on a scale Standard Error 0.22
Change From Baseline in DAS28-3 (CRP) Month 1 (n=33,35,37)	-1.61 scores on a scale Standard Error 0.19	-1.40 scores on a scale Standard Error 0.18	-0.73 scores on a scale Standard Error 0.18
Change From Baseline in DAS28-3 (CRP) Month 2 (n=33,33,32)	-2.32 scores on a scale Standard Error 0.19	-1.88 scores on a scale Standard Error 0.19	-1.24 scores on a scale Standard Error 0.19
Change From Baseline in DAS28-3 (CRP) Month 3 (n=33,33,31)	-2.25 scores on a scale Standard Error 0.19	-1.96 scores on a scale Standard Error 0.19	-1.57 scores on a scale Standard Error 0.19
Change From Baseline in DAS28-3 (CRP) Month 6 (n=31,29,29)	-2.54 scores on a scale Standard Error 0.19	-2.55 scores on a scale Standard Error 0.20	-1.52 scores on a scale Standard Error 0.19
Change From Baseline in DAS28-3 (CRP) Month 9 (n=30,28,24)	-2.92 scores on a scale Standard Error 0.20	-2.43 scores on a scale Standard Error 0.20	-1.76 scores on a scale Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline and Months 1, 2, 3, 6, 9, and 12

Population: FAS; n=number of participants assessed for the specified parameter at a given visit.

DAS28-4 (ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (millimeters per hour [mm/hour]) and Participant Global Assessment of disease activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4; higher score=more disease activity. DAS28-4 (ESR) ≤3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (ESR) <2.6 = remission.

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=36 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=36 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=37 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) Month 1 (n=34,35,37)	4.60 scores on a scale Standard Deviation 1.37	4.93 scores on a scale Standard Deviation 1.12	5.51 scores on a scale Standard Deviation 1.09
Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) Month 2 (n=32,33,31)	3.77 scores on a scale Standard Deviation 1.34	4.36 scores on a scale Standard Deviation 1.40	5.05 scores on a scale Standard Deviation 1.26
Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) Month 3 (n=33,33,31)	3.66 scores on a scale Standard Deviation 1.16	4.12 scores on a scale Standard Deviation 1.31	4.63 scores on a scale Standard Deviation 1.63
Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) Month 6 (n=30,29,28)	3.32 scores on a scale Standard Deviation 1.45	3.51 scores on a scale Standard Deviation 1.20	4.75 scores on a scale Standard Deviation 1.76
Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) Month 9 (n=30,28,24)	3.06 scores on a scale Standard Deviation 1.27	3.58 scores on a scale Standard Deviation 1.10	4.17 scores on a scale Standard Deviation 1.91
Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) Month 12 (n=27,26,20)	3.02 scores on a scale Standard Deviation 1.22	3.47 scores on a scale Standard Deviation 1.36	4.13 scores on a scale Standard Deviation 1.76
Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) Baseline (n=36,36,37)	6.25 scores on a scale Standard Deviation 0.94	6.50 scores on a scale Standard Deviation 0.75	6.44 scores on a scale Standard Deviation 0.78

SECONDARY outcome

Timeframe: Months 1, 2, 3, 6, 9, and 12

Population: FAS; n=number of participants assessed for the specified parameter at a given visit.

DAS28-4 (ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (millimeters per hour [mm/hour]) and Participant Global Assessment of disease activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4; higher score=more disease activity.

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=34 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=35 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=37 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Change From Baseline in DAS28-4 (ESR) Month 1 (n=34,35,37)	-1.77 scores on a scale Standard Error 0.21	-1.57 scores on a scale Standard Error 0.21	-0.94 scores on a scale Standard Error 0.20
Change From Baseline in DAS28-4 (ESR) Month 2 (n=32,33,31)	-2.59 scores on a scale Standard Error 0.22	-2.08 scores on a scale Standard Error 0.21	-1.41 scores on a scale Standard Error 0.21
Change From Baseline in DAS28-4 (ESR) Month 3 (n=33,33,31)	-2.69 scores on a scale Standard Error 0.21	-2.35 scores on a scale Standard Error 0.21	-1.80 scores on a scale Standard Error 0.21
Change From Baseline in DAS28-4 (ESR) Month 6 (n=30,29,28)	-3.02 scores on a scale Standard Error 0.22	-2.81 scores on a scale Standard Error 0.22	-1.73 scores on a scale Standard Error 0.22
Change From Baseline in DAS28-4 (ESR) Month 9 (n=30,28,24)	-3.29 scores on a scale Standard Error 0.22	-2.72 scores on a scale Standard Error 0.22	-2.14 scores on a scale Standard Error 0.23
Change From Baseline in DAS28-4 (ESR) Month 12 (n=27,26,20)	-3.31 scores on a scale Standard Error 0.22	-2.84 scores on a scale Standard Error 0.22	-2.18 scores on a scale Standard Error 0.24

SECONDARY outcome

Timeframe: Months 1, 2, 3, 6, 9, and 12

Population: FAS NRI; n=number of participants assessed for the specified parameter at a given visit.

DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28 categorical responses define a good (absolute: <3.2 or >1.2 improvement from baseline [BL]), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: >5.1 or <0.6 change from BL).

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=34 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=36 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=37 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) Month 1 (n=33,35,37)	75.76 percentage of participants	71.43 percentage of participants	43.24 percentage of participants
Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) Month 2 (n=34,36,37)	91.18 percentage of participants	80.56 percentage of participants	56.76 percentage of participants
Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) Month 3 (n=34,36,37)	91.18 percentage of participants	77.78 percentage of participants	56.76 percentage of participants
Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) Month 6 (n=34,36,37)	88.24 percentage of participants	77.78 percentage of participants	54.05 percentage of participants
Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) Month 9 (n=34,36,37)	79.41 percentage of participants	69.44 percentage of participants	45.95 percentage of participants
Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) Month 12 (n=34,36,37)	82.35 percentage of participants	72.22 percentage of participants	45.95 percentage of participants

SECONDARY outcome

Timeframe: Months 1, 2, 3, 6, 9, and 12

Population: FAS NRI; n=number of participants assessed for the specified parameter at a given visit.

DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3(CRP) ≤3.2 implied low disease activity.

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=34 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=36 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=37 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 Month 1 (n=33,35,37)	33.33 percentage of participants	17.14 percentage of participants	10.81 percentage of participants
Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 Month 2 (n=34,36,37)	50.00 percentage of participants	36.11 percentage of participants	21.62 percentage of participants
Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 Month 3 (n=34,36,37)	50.00 percentage of participants	41.67 percentage of participants	21.62 percentage of participants
Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 Month 6 (n=34,36,37)	61.76 percentage of participants	55.56 percentage of participants	27.03 percentage of participants
Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 Month 9 (n=34,36,37)	64.71 percentage of participants	58.33 percentage of participants	29.33 percentage of participants
Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 Month 12 (n=34,36,37)	61.76 percentage of participants	50.00 percentage of participants	27.03 percentage of participants

SECONDARY outcome

Timeframe: Months 1, 2, 3, 6, 9, and 12

Population: FAS NRI; n=number of participants assessed for the specified parameter at a given visit.

DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3(CRP) <2.6 implied remission.

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=34 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=36 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=37 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Percentage of Participants With DAS28-3 (CRP) Score <2.6 Month 1 (n=33,35,37)	18.18 percentage of participants	5.71 percentage of participants	5.41 percentage of participants
Percentage of Participants With DAS28-3 (CRP) Score <2.6 Month 2 (n=34,36,37)	35.29 percentage of participants	16.67 percentage of participants	8.11 percentage of participants
Percentage of Participants With DAS28-3 (CRP) Score <2.6 Month 3 (n=34,36,37)	32.35 percentage of participants	22.22 percentage of participants	13.51 percentage of participants
Percentage of Participants With DAS28-3 (CRP) Score <2.6 Month 6 (n=34,36,37)	47.06 percentage of participants	33.33 percentage of participants	16.22 percentage of participants
Percentage of Participants With DAS28-3 (CRP) Score <2.6 Month 9 (n=34,36,37)	50.00 percentage of participants	38.89 percentage of participants	18.92 percentage of participants
Percentage of Participants With DAS28-3 (CRP) Score <2.6 Month 12 (n=34,36,37)	47.06 percentage of participants	33.33 percentage of participants	13.51 percentage of participants

SECONDARY outcome

Timeframe: Months 1, 2, 3, 6, 9, and 12

Population: FAS NRI; n=number of participants assessed for the specified parameter at a given visit.

DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Participant's Global Assessment of Disease Activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28 categorical responses define a good (absolute: <3.2 or >1.2 improvement from BL), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: >5.1 or <0.6 change from BL).

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=34 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=35 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=37 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) Month 1 (n=34,35,37)	67.65 percentage of participants	62.86 percentage of participants	29.73 percentage of participants
Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) Month 2 (n=32,33,31)	85.29 percentage of participants	69.44 percentage of participants	59.46 percentage of participants
Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) Month 3 (n=33,33,31)	91.18 percentage of participants	69.44 percentage of participants	51.35 percentage of participants
Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) Month 6 (n=30,29,28)	85.29 percentage of participants	77.78 percentage of participants	51.35 percentage of participants
Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) Month 9 (n=30,28,24)	82.35 percentage of participants	72.22 percentage of participants	45.95 percentage of participants
Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) Month 12 (n=27,26,20)	79.41 percentage of participants	69.44 percentage of participants	45.95 percentage of participants

SECONDARY outcome

Timeframe: Months 1, 2, 3, 6, 9, and 12

Population: FAS NRI; n=number of participants assessed for the specified parameter at a given visit.

DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Participant's Global Assessment of Disease Activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28-4(ESR) ≤3.2 implied low disease activity.

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=34 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=36 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=37 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Percentage of Participants With DAS28-4 (ESR) ≤3.2 Month 1 (n=34,35,37)	20.59 percentage of participants	8.57 percentage of participants	2.70 percentage of participants
Percentage of Participants With DAS28-4 (ESR) ≤3.2 Month 2 (n=34,36,37)	35.29 percentage of participants	13.89 percentage of participants	8.11 percentage of participants
Percentage of Participants With DAS28-4 (ESR) ≤3.2 Month 3 (n=34,36,37)	32.35 percentage of participants	30.56 percentage of participants	13.51 percentage of participants
Percentage of Participants With DAS28-4 (ESR) ≤3.2 Month 6 (n=34,36,37)	41.18 percentage of participants	27.78 percentage of participants	18.92 percentage of participants
Percentage of Participants With DAS28-4 (ESR) ≤3.2 Month 9 (n=34,36,37)	44.12 percentage of participants	33.33 percentage of participants	18.92 percentage of participants
Percentage of Participants With DAS28-4 (ESR) ≤3.2 Month 12 (n=34,36,37)	50.00 percentage of participants	30.56 percentage of participants	16.22 percentage of participants

SECONDARY outcome

Timeframe: Months 1, 2, 3, 6, 9, and 12

Population: FAS NRI; n=number of participants assessed for the specified parameter at a given visit.

DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Participant's Global Assessment of Disease Activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28-4(ESR) <2.6 implied remission.

Outcome measures

Measure	Tofacitinib (CP-690,550) Plus MTX n=34 Participants Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=36 Participants Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=37 Participants Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Percentage of Participants With DAS28-4 (ESR) <2.6 Month 12 (n=34,36,37)	32.35 percentage of participants	19.44 percentage of participants	13.51 percentage of participants
Percentage of Participants With DAS28-4 (ESR) <2.6 Month 1 (n=34,35,37)	5.88 percentage of participants	2.86 percentage of participants	0.00 percentage of participants
Percentage of Participants With DAS28-4 (ESR) <2.6 Month 2 (n=34,36,37)	17.65 percentage of participants	5.56 percentage of participants	2.70 percentage of participants
Percentage of Participants With DAS28-4 (ESR) <2.6 Month 3 (n=34,36,37)	23.53 percentage of participants	2.78 percentage of participants	13.51 percentage of participants
Percentage of Participants With DAS28-4 (ESR) <2.6 Month 6 (n=34,36,37)	29.41 percentage of participants	13.89 percentage of participants	13.51 percentage of participants
Percentage of Participants With DAS28-4 (ESR) <2.6 Month 9 (n=34,36,37)	35.29 percentage of participants	13.89 percentage of participants	16.22 percentage of participants

Adverse Events

Tofacitinib (CP-690,550) Plus MTX

Serious events: 2 serious events

Other events: 24 other events

Deaths: 0 deaths

Tofacitinib (CP-690,550)

Serious events: 1 serious events

Other events: 31 other events

Deaths: 0 deaths

Methotrexate

Serious events: 2 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Measure	Tofacitinib (CP-690,550) Plus MTX n=36 participants at risk Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=36 participants at risk Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=37 participants at risk Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Cardiac disorders Angina pectoris	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Hematochezia	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Cholelithiasis	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Anal abscess	2.8% 1/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Foot deformity	2.8% 1/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.

Other adverse events

Measure	Tofacitinib (CP-690,550) Plus MTX n=36 participants at risk Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Tofacitinib (CP-690,550) n=36 participants at risk Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.	Methotrexate n=37 participants at risk Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care.
Blood and lymphatic system disorders Anaemia	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Leukopenia	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Lymph node pain	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Lymphopenia	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Macrocytosis	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Neutropenia	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Neutrophilia	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Normochromic normocytic anaemia	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Thrombocytosis	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Angina pectoris	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Myocardial ischaemia	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Palpitations	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Ear pruritus	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Vertigo	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Endocrine disorders Hypothyroidism	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Eye disorders Eye disorder	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Eye disorders Lacrimation increased	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Eye disorders Scleritis	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Eye disorders Visual acuity reduced	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Eye disorders Xerophthalmia	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal distension	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain upper	5.6% 2/36 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	5.4% 2/37 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal tenderness	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Aphthous stomatitis	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Constipation	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	5.6% 2/36 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dry mouth	5.6% 2/36 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dyspepsia	5.6% 2/36 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Food poisoning	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastric disorder	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastritis	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	13.9% 5/36 • Number of events 5 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	10.8% 4/37 • Number of events 4 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Hyperchlorhydria	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Irritable bowel syndrome	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Stomatitis	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
General disorders Chest pain	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
General disorders Local swelling	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
General disorders Malaise	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
General disorders Non-cardiac chest pain	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
General disorders Pyrexia	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Cholelithiasis	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Hepatic steatosis	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Hypertransaminasaemia	5.6% 2/36 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	5.4% 2/37 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Acute tonsillitis	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Anal abscess	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Bronchitis	8.3% 3/36 • Number of events 3 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Folliculitis	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Fungal skin infection	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Furuncle	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Gastroenteritis	5.6% 2/36 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Influenza	5.6% 2/36 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	5.6% 2/36 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Nasopharyngitis	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Oral fungal infection	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Oral herpes	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Pharyngitis	5.6% 2/36 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	8.3% 3/36 • Number of events 3 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	5.4% 2/37 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Pharyngotonsillitis	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Respiratory tract infection	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Rhinitis	5.6% 2/36 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Sinusitis	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Tonsillitis	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Tooth abscess	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Tooth infection	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Upper respiratory tract infection	8.3% 3/36 • Number of events 3 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	5.6% 2/36 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	5.4% 2/37 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Urinary tract infection	5.6% 2/36 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	5.6% 2/36 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Viral upper respiratory tract infection	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Vulvovaginitis	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Toxicity to various agents	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Investigations Alanine aminotransferase increased	16.7% 6/36 • Number of events 6 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	13.5% 5/37 • Number of events 5 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Investigations Aspartate aminotransferase increased	5.6% 2/36 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	8.1% 3/37 • Number of events 3 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Investigations Blood bicarbonate decreased	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Investigations Blood cholesterol increased	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Investigations Blood creatine phosphokinase increased	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	8.3% 3/36 • Number of events 3 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Investigations Blood glucose increased	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Investigations Gamma-glutamyltransferase increased	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	5.4% 2/37 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Investigations Haemoglobin decreased	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Investigations Hepatic enzyme increased	5.6% 2/36 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	5.4% 2/37 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Investigations Liver function test abnormal	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Investigations Red blood cell count decreased	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Investigations Transaminases increased	5.6% 2/36 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Investigations Weight increased	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	5.6% 2/36 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypercholesterolaemia	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypertriglyceridaemia	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	5.4% 2/37 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Increased appetite	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Arthralgia	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Back pain	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	5.4% 2/37 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Joint swelling	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Myalgia	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	5.6% 2/36 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	13.5% 5/37 • Number of events 5 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Rheumatoid nodule	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Tendonitis	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dizziness	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	8.3% 3/36 • Number of events 3 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	5.6% 2/36 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	5.4% 2/37 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Hypoaesthesia	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Sciatica	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Tension headache	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Depression	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Insomnia	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Dysuria	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Urinary incontinence	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Breast tenderness	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Menorrhagia	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	5.6% 2/36 • Number of events 2 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Sexual dysfunction	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Uterine fibrosis	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Vaginal discharge	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Cough	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pharyngeal inflammation	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Acne	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Alopecia	8.3% 3/36 • Number of events 3 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	8.1% 3/37 • Number of events 3 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Diffuse alopecia	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Ingrowing nail	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.7% 1/37 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Pruritus	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Rash	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	11.1% 4/36 • Number of events 4 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Rosacea	0.00% 0/36 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Vascular disorders Hypertension	2.8% 1/36 • Number of events 1 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	16.7% 6/36 • Number of events 6 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/37 • Adverse events were collected up to 28 calendar days after the last administration of investigational product. The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.

Additional Information

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Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place