Trial Outcomes & Findings for The Safety And Efficacy Of Maintenance Therapy With CP-690,550 (NCT NCT01393899)

Last Updated: 2017-01-09

Results Overview

Clinical response-100 was defined as a reduction in CDAI score of at least 100 points from baseline of the parent A3921083 study. Clinical remission was a CDAI score \<150 points. CDAI is a composite index consisting of a weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general well-being, occurrence of extra-intestinal symptoms, need for anti-diarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's diary kept while on study. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

180 participants

Primary outcome timeframe

Week 26

Results posted on

2017-01-09

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo (two placebo tablets) to match tofacitinib for oral administration BID for 26 weeks.	Tofacitinib 5 mg BID Tofacitinib 5 mg (one placebo tablet and one tofacitinib tablet) for oral administration at a dose of 5 mg BID for 26 weeks.	Tofacitinib 10 mg BID Tofacitinib 10 mg (two tofacitinib tablets) for oral administration at a dose of 10 mg BID for 26 weeks.
Overall Study STARTED	59	60	61
Overall Study COMPLETED	27	32	38
Overall Study NOT COMPLETED	32	28	23

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo (two placebo tablets) to match tofacitinib for oral administration BID for 26 weeks.	Tofacitinib 5 mg BID Tofacitinib 5 mg (one placebo tablet and one tofacitinib tablet) for oral administration at a dose of 5 mg BID for 26 weeks.	Tofacitinib 10 mg BID Tofacitinib 10 mg (two tofacitinib tablets) for oral administration at a dose of 10 mg BID for 26 weeks.
Overall Study Study terminated by sponsor	1	0	1
Overall Study Other	1	0	0
Overall Study Withdrawal by Subject	2	2	1
Overall Study Lost to Follow-up	0	0	1
Overall Study Does not meet entrance criteria	1	0	1
Overall Study Lack of Efficacy	26	21	16
Overall Study Adverse Event	1	5	3

Baseline Characteristics

The Safety And Efficacy Of Maintenance Therapy With CP-690,550

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=59 Participants Placebo (two placebo tablets) to match tofacitinib for oral administration BID for 26 weeks.	Tofacitinib 5 mg BID n=60 Participants Tofacitinib 5 mg (one placebo tablet and one tofacitinib tablet) for oral administration at a dose of 5 mg BID for 26 weeks.	Tofacitinib 10 mg BID n=61 Participants Tofacitinib 10 mg (two tofacitinib tablets) for oral administration at a dose of 10 mg BID for 26 weeks.	Total n=180 Participants Total of all reporting groups
Age, Customized Less than or equal to (<=)18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Customized Between 18 and 44 years	34 Participants n=5 Participants	44 Participants n=7 Participants	40 Participants n=5 Participants	118 Participants n=4 Participants
Age, Customized Between 45 and 64 years	23 Participants n=5 Participants	15 Participants n=7 Participants	20 Participants n=5 Participants	58 Participants n=4 Participants
Age, Customized More than or equal to (>=)65 years	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Gender Female	32 Participants n=5 Participants	30 Participants n=7 Participants	24 Participants n=5 Participants	86 Participants n=4 Participants
Gender Male	27 Participants n=5 Participants	30 Participants n=7 Participants	37 Participants n=5 Participants	94 Participants n=4 Participants

PRIMARY outcome

Timeframe: Week 26

Population: Modified full analysis set (mFAS), defined as all randomized participants who received at least 1 dose of investigational product (ie, active or placebo study medication) in this study and who were randomized into 1 of the tofacitinib (CP-690,550) dose groups in Study A3921083.

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Placebo (two placebo tablets) to match tofacitinib for oral administration BID for 26 weeks.	Tofacitinib 5 mg BID n=43 Participants Tofacitinib 5 mg (one placebo tablet and one tofacitinib tablet) for oral administration at a dose of 5 mg BID for 26 weeks.	Tofacitinib 10 mg BID n=43 Participants Tofacitinib 10 mg (two tofacitinib tablets) for oral administration at a dose of 10 mg BID for 26 weeks.
Percentage of Participants With Clinical Response-100 (as Defined by a Decrease in Crohn's Disease Activity Index [CDAI] Score of at Least 100 Points From Baseline) or Clinical Remission (CDAI Score Less Than [<]150) at Week 26	38.10 Percentage of participants Interval 27.94 to 49.16	39.53 Percentage of participants Interval 29.39 to 50.46	55.81 Percentage of participants Interval 44.92 to 66.28

SECONDARY outcome

Timeframe: Weeks 4, 8, 12 and 20

Population: mFAS

Clinical response-100 was defined as a reduction in CDAI score of at least 100 points from baseline of the parent A3921083 study. Clinical remission was a CDAI score \<150 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for anti-diarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity.

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Placebo (two placebo tablets) to match tofacitinib for oral administration BID for 26 weeks.	Tofacitinib 5 mg BID n=43 Participants Tofacitinib 5 mg (one placebo tablet and one tofacitinib tablet) for oral administration at a dose of 5 mg BID for 26 weeks.	Tofacitinib 10 mg BID n=43 Participants Tofacitinib 10 mg (two tofacitinib tablets) for oral administration at a dose of 10 mg BID for 26 weeks.
Percentage of Participants With Clinical Response-100 or Clinical Remission at Weeks 4, 8, 12 and 20 Week 12	50.00 Percentage of participants Interval 39.12 to 60.88	55.81 Percentage of participants Interval 44.92 to 66.28	53.49 Percentage of participants Interval 42.64 to 64.08
Percentage of Participants With Clinical Response-100 or Clinical Remission at Weeks 4, 8, 12 and 20 Week 4	73.81 Percentage of participants Interval 63.16 to 82.62	74.42 Percentage of participants Interval 63.96 to 83.05	79.07 Percentage of participants Interval 68.98 to 86.96
Percentage of Participants With Clinical Response-100 or Clinical Remission at Weeks 4, 8, 12 and 20 Week 8	66.67 Percentage of participants Interval 55.69 to 76.37	67.44 Percentage of participants Interval 56.64 to 76.95	58.14 Percentage of participants Interval 47.22 to 68.46
Percentage of Participants With Clinical Response-100 or Clinical Remission at Weeks 4, 8, 12 and 20 Week 20	40.48 Percentage of participants Interval 30.13 to 51.55	39.53 Percentage of participants Interval 29.39 to 50.46	51.16 Percentage of participants Interval 40.38 to 61.86

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 20 and 26

Population: mFAS

Clinical response-100 was defined as a reduction in CDAI score from baseline of at least 100 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for anti-diarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity.

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Placebo (two placebo tablets) to match tofacitinib for oral administration BID for 26 weeks.	Tofacitinib 5 mg BID n=43 Participants Tofacitinib 5 mg (one placebo tablet and one tofacitinib tablet) for oral administration at a dose of 5 mg BID for 26 weeks.	Tofacitinib 10 mg BID n=43 Participants Tofacitinib 10 mg (two tofacitinib tablets) for oral administration at a dose of 10 mg BID for 26 weeks.
Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 Week 4	73.81 Percentage of participants Interval 63.16 to 82.62	72.09 Percentage of participants Interval 61.49 to 81.04	76.74 Percentage of participants Interval 66.45 to 85.02
Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 Week 8	66.67 Percentage of participants Interval 55.69 to 76.37	62.79 Percentage of participants Interval 51.88 to 72.75	58.14 Percentage of participants Interval 47.22 to 68.46
Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 Week 12	50.00 Percentage of participants Interval 39.12 to 60.88	55.81 Percentage of participants Interval 44.92 to 66.28	51.16 Percentage of participants Interval 40.38 to 61.86
Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 Week 20	38.10 Percentage of participants Interval 27.94 to 49.16	39.53 Percentage of participants Interval 29.39 to 50.46	51.16 Percentage of participants Interval 40.38 to 61.86
Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 Week 26	35.71 Percentage of participants Interval 25.77 to 46.74	37.21 Percentage of participants Interval 27.25 to 48.12	55.81 Percentage of participants Interval 44.92 to 66.28

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 20 and 26

Population: mFAS

Clinical remission was a CDAI score \<150 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for anti-diarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity.

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Placebo (two placebo tablets) to match tofacitinib for oral administration BID for 26 weeks.	Tofacitinib 5 mg BID n=43 Participants Tofacitinib 5 mg (one placebo tablet and one tofacitinib tablet) for oral administration at a dose of 5 mg BID for 26 weeks.	Tofacitinib 10 mg BID n=43 Participants Tofacitinib 10 mg (two tofacitinib tablets) for oral administration at a dose of 10 mg BID for 26 weeks.
Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 Week 8	47.62 Percentage of participants Interval 36.84 to 58.58	48.84 Percentage of participants Interval 38.14 to 59.62	39.53 Percentage of participants Interval 29.39 to 50.46
Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 Week 12	33.33 Percentage of participants Interval 23.63 to 44.31	46.51 Percentage of participants Interval 35.92 to 57.36	34.88 Percentage of participants Interval 25.14 to 45.75
Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 Week 26	28.57 Percentage of participants Interval 19.43 to 39.35	37.21 Percentage of participants Interval 27.25 to 48.12	41.86 Percentage of participants Interval 31.54 to 52.78
Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 Week 4	52.38 Percentage of participants Interval 41.42 to 63.16	55.81 Percentage of participants Interval 44.92 to 66.28	58.14 Percentage of participants Interval 47.22 to 68.46
Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 Week 20	30.95 Percentage of participants Interval 21.52 to 41.84	32.56 Percentage of participants Interval 23.05 to 43.36	39.53 Percentage of participants Interval 29.39 to 50.46

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 20 and 26

Population: mFAS

Outcome measures

Outcome measures
Measure	Placebo n=25 Participants Placebo (two placebo tablets) to match tofacitinib for oral administration BID for 26 weeks.	Tofacitinib 5 mg BID n=28 Participants Tofacitinib 5 mg (one placebo tablet and one tofacitinib tablet) for oral administration at a dose of 5 mg BID for 26 weeks.	Tofacitinib 10 mg BID n=26 Participants Tofacitinib 10 mg (two tofacitinib tablets) for oral administration at a dose of 10 mg BID for 26 weeks.
Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study Week 4	72.00 Percentage of participants Interval 57.42 to 83.68	78.57 Percentage of participants Interval 65.41 to 88.34	80.77 Percentage of participants Interval 67.23 to 90.34
Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study Week 8	64.00 Percentage of participants Interval 49.2 to 76.97	64.29 Percentage of participants Interval 50.42 to 76.5	50.00 Percentage of participants Interval 35.93 to 64.07
Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study Week 12	40.00 Percentage of participants Interval 26.53 to 54.77	64.29 Percentage of participants Interval 50.42 to 76.5	42.31 Percentage of participants Interval 28.86 to 56.71
Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study Week 20	36.00 Percentage of participants Interval 23.03 to 50.8	42.86 Percentage of participants Interval 29.87 to 56.67	46.15 Percentage of participants Interval 32.36 to 60.43
Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study Week 26	28.00 Percentage of participants Interval 16.32 to 42.58	39.29 Percentage of participants Interval 26.65 to 53.16	50.00 Percentage of participants Interval 35.93 to 64.07

SECONDARY outcome

Timeframe: Weeks 20 and 26

Population: mFAS

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Placebo (two placebo tablets) to match tofacitinib for oral administration BID for 26 weeks.	Tofacitinib 5 mg BID n=43 Participants Tofacitinib 5 mg (one placebo tablet and one tofacitinib tablet) for oral administration at a dose of 5 mg BID for 26 weeks.	Tofacitinib 10 mg BID n=43 Participants Tofacitinib 10 mg (two tofacitinib tablets) for oral administration at a dose of 10 mg BID for 26 weeks.
Percentage of Participants in Sustained Clinical Remission (Defined as Being in Clinical Remission at Both Weeks 20 and 26) in the Maintenance Phase	21.43 Percentage of participants Interval 13.37 to 31.71	23.26 Percentage of participants Interval 14.98 to 33.55	39.53 Percentage of participants Interval 29.39 to 50.46

SECONDARY outcome

Timeframe: Weeks 20 and 26

Population: mFAS

Clinical response-100 was defined as a reduction in CDAI score from baseline of at least 100 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general well-being, occurrence of extra-intestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity.

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Placebo (two placebo tablets) to match tofacitinib for oral administration BID for 26 weeks.	Tofacitinib 5 mg BID n=43 Participants Tofacitinib 5 mg (one placebo tablet and one tofacitinib tablet) for oral administration at a dose of 5 mg BID for 26 weeks.	Tofacitinib 10 mg BID n=43 Participants Tofacitinib 10 mg (two tofacitinib tablets) for oral administration at a dose of 10 mg BID for 26 weeks.
Percentage of Participants With Sustained Clinical Response-100 (Defined as Having at Least a Clinical Response-100 at Both Weeks 20 and 26 From the A3921083 Baseline) in the Maintenance Phase	33.33 Percentage of participants Interval 23.63 to 44.31	25.58 Percentage of participants Interval 16.95 to 36.04	51.16 Percentage of participants Interval 40.38 to 61.86

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 20 and 26

Population: mFAS

CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general wellbeing, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Placebo (two placebo tablets) to match tofacitinib for oral administration BID for 26 weeks.	Tofacitinib 5 mg BID n=43 Participants Tofacitinib 5 mg (one placebo tablet and one tofacitinib tablet) for oral administration at a dose of 5 mg BID for 26 weeks.	Tofacitinib 10 mg BID n=43 Participants Tofacitinib 10 mg (two tofacitinib tablets) for oral administration at a dose of 10 mg BID for 26 weeks.
CDAI Score by Week Week 4	168.24 Score on a scale Standard Deviation 103.18 • Interval -117.0 to 225.0	133.48 Score on a scale Standard Deviation 89.94 • Interval -105.0 to 241.0	143.45 Score on a scale Standard Deviation 84.26 • Interval -132.0 to 276.0
CDAI Score by Week Baseline	135.05 Score on a scale Standard Deviation 69.83 • Interval -112.0 to 273.0	127.23 Score on a scale Standard Deviation 60.46 • Interval -131.0 to 314.0	133.98 Score on a scale Standard Deviation 63.31 • Interval -133.0 to 198.0
CDAI Score by Week Week 8	171.87 Score on a scale Standard Deviation 109.18 • Interval -137.0 to 474.0	149.78 Score on a scale Standard Deviation 99.56 • Interval -126.0 to 266.0	165.69 Score on a scale Standard Deviation 95.46 • Interval -133.0 to 186.0
CDAI Score by Week Week 12	181.38 Score on a scale Standard Deviation 108.68 • Interval -152.0 to 199.0	158.56 Score on a scale Standard Deviation 119.41 • Interval -113.0 to 300.0	152.93 Score on a scale Standard Deviation 82.77 • Interval -187.0 to 148.0
CDAI Score by Week Week 20	161.76 Score on a scale Standard Deviation 91.65 • Interval -176.0 to 163.0	151.74 Score on a scale Standard Deviation 106.09 • Interval -106.0 to 164.0	112.32 Score on a scale Standard Deviation 85.47 • Interval -203.0 to 106.0
CDAI Score by Week Week 26	137.05 Score on a scale Standard Deviation 77.65	134.77 Score on a scale Standard Deviation 80.22	110.77 Score on a scale Standard Deviation 76.30

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 20 and 26

Population: mFAS

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Placebo (two placebo tablets) to match tofacitinib for oral administration BID for 26 weeks.	Tofacitinib 5 mg BID n=43 Participants Tofacitinib 5 mg (one placebo tablet and one tofacitinib tablet) for oral administration at a dose of 5 mg BID for 26 weeks.	Tofacitinib 10 mg BID n=43 Participants Tofacitinib 10 mg (two tofacitinib tablets) for oral administration at a dose of 10 mg BID for 26 weeks.
Change From Baseline in CDAI Score by Week Week 4	33.17 Score on a scale Standard Deviation 76.41 • Interval -112.0 to 273.0	5.85 Score on a scale Standard Deviation 69.52 • Interval -131.0 to 314.0	11.02 Score on a scale Standard Deviation 72.22 • Interval -133.0 to 198.0
Change From Baseline in CDAI Score by Week Week 8	39.85 Score on a scale Standard Deviation 83.68 • Interval -117.0 to 225.0	20.32 Score on a scale Standard Deviation 69.59 • Interval -105.0 to 241.0	101.96 Score on a scale Standard Deviation 101.96 • Interval -132.0 to 276.0
Change From Baseline in CDAI Score by Week Week 12	52.81 Score on a scale Standard Deviation 113.91 • Interval -137.0 to 474.0	32.29 Score on a scale Standard Deviation 88.35 • Interval -126.0 to 266.0	24.07 Score on a scale Standard Deviation 84.46 • Interval -133.0 to 186.0
Change From Baseline in CDAI Score by Week Week 20	32.44 Score on a scale Standard Deviation 96.18 • Interval -152.0 to 199.0	36.83 Score on a scale Standard Deviation 90.92 • Interval -113.0 to 300.0	-14.36 Score on a scale Standard Deviation 78.58 • Interval -187.0 to 148.0
Change From Baseline in CDAI Score by Week Week 26	1.50 Score on a scale Standard Deviation 93.91 • Interval -176.0 to 163.0	17.36 Score on a scale Standard Deviation 79.81 • Interval -106.0 to 164.0	-16.35 Score on a scale Standard Deviation 75.65 • Interval -203.0 to 106.0

SECONDARY outcome

Timeframe: Weeks 4, 8 12, 20 and 26

Population: mFAS, n=number of participants remaining at risk

Time to relapse was defined as increase in CDAI of more than (\>)100 points from the maintenance phase baseline and a CDAI score of \>220 points, or an increase to or above the baseline CDAI score in A3921083. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general wellbeing, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity.

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Placebo (two placebo tablets) to match tofacitinib for oral administration BID for 26 weeks.	Tofacitinib 5 mg BID n=43 Participants Tofacitinib 5 mg (one placebo tablet and one tofacitinib tablet) for oral administration at a dose of 5 mg BID for 26 weeks.	Tofacitinib 10 mg BID n=43 Participants Tofacitinib 10 mg (two tofacitinib tablets) for oral administration at a dose of 10 mg BID for 26 weeks.
Kaplan-Meier Estimate of the Rate of Time to Relapse Week 8 (n=32,35,32)	21.90 Percent Probability Interval 14.27 to 30.6	14.47 Percent Probability Interval 8.35 to 22.21	23.51 Percent Probability Interval 15.73 to 32.21
Kaplan-Meier Estimate of the Rate of Time to Relapse Week 4 (n=35,38,38)	14.58 Percent Probability Interval 8.42 to 22.37	7.14 Percent Probability Interval 3.15 to 13.34	11.63 Percent Probability Interval 6.3 to 18.73
Kaplan-Meier Estimate of the Rate of Time to Relapse Week 12 (n=24,30,27)	39.18 Percent Probability Interval 29.4 to 48.8	26.69 Percent Probability Interval 18.32 to 35.77	31.09 Percent Probability Interval 22.19 to 40.38
Kaplan-Meier Estimate of the Rate of Time to Relapse Week 20 (n=19,22,23)	51.85 Percent Probability Interval 41.33 to 61.37	39.11 Percent Probability Interval 29.35 to 48.74	38.95 Percent Probability Interval 29.16 to 48.6
Kaplan-Meier Estimate of the Rate of Time to Relapse Week 26 (n=1,1,2)	69.59 Percent Probability Interval 48.73 to 83.29	50.69 Percent Probability Interval 38.96 to 61.27	43.31 Percent Probability Interval 32.6 to 53.54

SECONDARY outcome

Timeframe: Week 26

Population: mFAS who were on steroids at A3921084 Baseline

Clinical remission was a CDAI \<150 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general wellbeing, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body eight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity.

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants Placebo (two placebo tablets) to match tofacitinib for oral administration BID for 26 weeks.	Tofacitinib 5 mg BID n=11 Participants Tofacitinib 5 mg (one placebo tablet and one tofacitinib tablet) for oral administration at a dose of 5 mg BID for 26 weeks.	Tofacitinib 10 mg BID n=15 Participants Tofacitinib 10 mg (two tofacitinib tablets) for oral administration at a dose of 10 mg BID for 26 weeks.
Percentage of Participants Achieving a Steroid-Free Clinical Remission at Week 26 of the Maintenance Phase - Among Participants on Steroids at A3921084 Baseline	16.67 Percentage of participants Interval 4.52 to 38.55	27.27 Percentage of participants Interval 10.48 to 51.08	33.33 Percentage of participants Interval 17.2 to 53.17

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 20 and 26

Population: mFAS

The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Placebo (two placebo tablets) to match tofacitinib for oral administration BID for 26 weeks.	Tofacitinib 5 mg BID n=43 Participants Tofacitinib 5 mg (one placebo tablet and one tofacitinib tablet) for oral administration at a dose of 5 mg BID for 26 weeks.	Tofacitinib 10 mg BID n=43 Participants Tofacitinib 10 mg (two tofacitinib tablets) for oral administration at a dose of 10 mg BID for 26 weeks.
C-Reactive Protein (CRP) by Week Baseline	8.08 milligram per liter (mg/L) Standard Deviation 13.88 • Interval -3.3 to 110.6	7.08 milligram per liter (mg/L) Standard Deviation 10.83 • Interval -37.1 to 63.8	8.59 milligram per liter (mg/L) Standard Deviation 16.43 • Interval -53.3 to 21.4
C-Reactive Protein (CRP) by Week Week 4	16.08 milligram per liter (mg/L) Standard Deviation 24.62 • Interval -3.2 to 141.3	8.04 milligram per liter (mg/L) Standard Deviation 17.36 • Interval -40.3 to 17.5	7.62 milligram per liter (mg/L) Standard Deviation 15.03 • Interval -14.9 to 26.3
C-Reactive Protein (CRP) by Week Week 8	15.80 milligram per liter (mg/L) Standard Deviation 28.98 • Interval -4.5 to 74.8	8.03 milligram per liter (mg/L) Standard Deviation 10.86 • Interval -40.5 to 38.1	7.24 milligram per liter (mg/L) Standard Deviation 16.48 • Interval -6.7 to 11.4
C-Reactive Protein (CRP) by Week Week 12	15.49 milligram per liter (mg/L) Standard Deviation 17.80 • Interval -4.6 to 60.0	8.19 milligram per liter (mg/L) Standard Deviation 11.75 • Interval -34.8 to 43.7	5.57 milligram per liter (mg/L) Standard Deviation 13.52 • Interval -12.1 to 25.4
C-Reactive Protein (CRP) by Week Week 20	15.10 milligram per liter (mg/L) Standard Deviation 20.37 • Interval -0.4 to 140.0	10.07 milligram per liter (mg/L) Standard Deviation 14.56 • Interval -16.6 to 41.3	6.52 milligram per liter (mg/L) Standard Deviation 18.26 • Interval -11.4 to 8.6
C-Reactive Protein (CRP) by Week Week 26	27.70 milligram per liter (mg/L) Standard Deviation 41.76	13.00 milligram per liter (mg/L) Standard Deviation 13.65	3.57 milligram per liter (mg/L) Standard Deviation 3.55

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 20 and 26

Population: mFAS

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Placebo (two placebo tablets) to match tofacitinib for oral administration BID for 26 weeks.	Tofacitinib 5 mg BID n=43 Participants Tofacitinib 5 mg (one placebo tablet and one tofacitinib tablet) for oral administration at a dose of 5 mg BID for 26 weeks.	Tofacitinib 10 mg BID n=43 Participants Tofacitinib 10 mg (two tofacitinib tablets) for oral administration at a dose of 10 mg BID for 26 weeks.
Change From Baseline in CRP by Week Week 4	10.66 milligram per liter (mg/L) Standard Deviation 19.47 • Interval -3.3 to 110.6	0.84 milligram per liter (mg/L) Standard Deviation 12.52 • Interval -37.1 to 63.8	-0.97 milligram per liter (mg/L) Standard Deviation 10.81 • Interval -53.3 to 21.4
Change From Baseline in CRP by Week Week 8	10.33 milligram per liter (mg/L) Standard Deviation 24.33 • Interval -3.2 to 141.3	0.96 milligram per liter (mg/L) Standard Deviation 9.80 • Interval -40.3 to 17.5	1.29 milligram per liter (mg/L) Standard Deviation 7.24 • Interval -14.9 to 26.3
Change From Baseline in CRP by Week Week 12	11.78 milligram per liter (mg/L) Standard Deviation 17.85 • Interval -4.5 to 74.8	2.36 milligram per liter (mg/L) Standard Deviation 12.15 • Interval -40.5 to 38.1	0.39 milligram per liter (mg/L) Standard Deviation 3.66 • Interval -6.7 to 11.4
Change From Baseline in CRP by Week Week 20	11.48 milligram per liter (mg/L) Standard Deviation 19.25 • Interval -4.6 to 60.0	2.92 milligram per liter (mg/L) Standard Deviation 14.86 • Interval -34.8 to 43.7	0.91 milligram per liter (mg/L) Standard Deviation 6.75 • Interval -12.1 to 25.4
Change From Baseline in CRP by Week Week 26	24.07 milligram per liter (mg/L) Standard Deviation 40.90 • Interval -0.4 to 140.0	6.62 milligram per liter (mg/L) Standard Deviation 13.07 • Interval -16.6 to 41.3	0.59 milligram per liter (mg/L) Standard Deviation 3.75 • Interval -11.4 to 8.6

SECONDARY outcome

Timeframe: Baseline and Weeks 8, 12 and 26

Population: mFAS

Fecal calprotectin is an inflammatory marker for the gastrointestinal tract and considered as a measurement of neutrophil migration to the gastrointestinal tract. Higher values indicate more serious inflammation.

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Placebo (two placebo tablets) to match tofacitinib for oral administration BID for 26 weeks.	Tofacitinib 5 mg BID n=43 Participants Tofacitinib 5 mg (one placebo tablet and one tofacitinib tablet) for oral administration at a dose of 5 mg BID for 26 weeks.	Tofacitinib 10 mg BID n=43 Participants Tofacitinib 10 mg (two tofacitinib tablets) for oral administration at a dose of 10 mg BID for 26 weeks.
Fecal Calprotectin by Week Baseline	380.43 milligrams per kilogram (mg/kg) Standard Deviation 296.24 • Interval -829.0 to 1416.0	351.39 milligrams per kilogram (mg/kg) Standard Deviation 290.67 • Interval -567.0 to 474.0	399.33 milligrams per kilogram (mg/kg) Standard Deviation 346.98 • Interval -945.0 to 775.0
Fecal Calprotectin by Week Week 8	440.81 milligrams per kilogram (mg/kg) Standard Deviation 350.71 • Interval -410.0 to 986.0	295.39 milligrams per kilogram (mg/kg) Standard Deviation 272.25 • Interval -517.0 to 523.0	283.76 milligrams per kilogram (mg/kg) Standard Deviation 304.43 • Interval -764.0 to 472.0
Fecal Calprotectin by Week Week 12	441.40 milligrams per kilogram (mg/kg) Standard Deviation 336.51 • Interval -232.0 to 3426.0	351.59 milligrams per kilogram (mg/kg) Standard Deviation 303.08 • Interval -487.0 to 820.0	194.00 milligrams per kilogram (mg/kg) Standard Deviation 208.50 • Interval -606.8 to 312.28
Fecal Calprotectin by Week Week 26	939.11 milligrams per kilogram (mg/kg) Standard Deviation 1037.39	500.18 milligrams per kilogram (mg/kg) Standard Deviation 337.83	243.76 milligrams per kilogram (mg/kg) Standard Deviation 219.04

SECONDARY outcome

Timeframe: Weeks 8, 12 and 26

Population: mFAS

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Placebo (two placebo tablets) to match tofacitinib for oral administration BID for 26 weeks.	Tofacitinib 5 mg BID n=43 Participants Tofacitinib 5 mg (one placebo tablet and one tofacitinib tablet) for oral administration at a dose of 5 mg BID for 26 weeks.	Tofacitinib 10 mg BID n=43 Participants Tofacitinib 10 mg (two tofacitinib tablets) for oral administration at a dose of 10 mg BID for 26 weeks.
Change From Baseline in Fecal Calprotectin by Week Week 8	69.22 milligrams per kilogram (mg/kg) Standard Deviation 384.35 • Interval -829.0 to 1416.0	-59.73 milligrams per kilogram (mg/kg) Standard Deviation 216.36 • Interval -567.0 to 474.0	-123.95 milligrams per kilogram (mg/kg) Standard Deviation 336.67 • Interval -945.0 to 775.0
Change From Baseline in Fecal Calprotectin by Week Week 12	103.55 milligrams per kilogram (mg/kg) Standard Deviation 311.15 • Interval -410.0 to 986.0	-1.81 milligrams per kilogram (mg/kg) Standard Deviation 228.24 • Interval -517.0 to 523.0	-107.04 milligrams per kilogram (mg/kg) Standard Deviation 259.68 • Interval -764.0 to 472.0
Change From Baseline in Fecal Calprotectin by Week Week 26	579.10 milligrams per kilogram (mg/kg) Standard Deviation 870.77 • Interval -232.0 to 3426.0	154.17 milligrams per kilogram (mg/kg) Standard Deviation 349.49 • Interval -487.0 to 820.0	-33.75 milligrams per kilogram (mg/kg) Standard Deviation 204.25 • Interval -606.8 to 312.28

SECONDARY outcome

Timeframe: Pre-dose, 20 minutes, 40 minutes, 1 hour and 2 hours post-dose at Weeks 12 and 26/early termination visit

Population: Pharmacokinetic analysis set - included all participants who received at least 1 dose of study medication and had at least 1 measurable plasma concentration. n=number of observations above lower limit of quantification.

Plasma samples were collected from participants for the determination of tofacitinib concentrations. Only samples from tofacitinib-treated participants were subsequently analyzed. Plasma concentration data are summarized by nominal sample collection times specified in the protocol, and actual sample collection times may be different.

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants Placebo (two placebo tablets) to match tofacitinib for oral administration BID for 26 weeks.	Tofacitinib 5 mg BID n=48 Participants Tofacitinib 5 mg (one placebo tablet and one tofacitinib tablet) for oral administration at a dose of 5 mg BID for 26 weeks.	Tofacitinib 10 mg BID Tofacitinib 10 mg (two tofacitinib tablets) for oral administration at a dose of 10 mg BID for 26 weeks.
Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose Week 12, 0 hours (n=43, 40)	6.059 nanograms per milliliter (ng/mL) Standard Deviation 7.4264 • Interval 0.0 to 28.7	6.832 nanograms per milliliter (ng/mL) Standard Deviation 5.7271 • Interval 0.0 to 20.5	—
Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose Week 12, 20 minutes (n=45, 40)	31.56 nanograms per milliliter (ng/mL) Standard Deviation 21.904 • Interval 0.12 to 76.4	58.53 nanograms per milliliter (ng/mL) Standard Deviation 53.579 • Interval 0.0 to 156.0	—
Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose Week 12, 40 minutes (n=47, 41)	47.05 nanograms per milliliter (ng/mL) Standard Deviation 23.904 • Interval 0.685 to 96.1	85.23 nanograms per milliliter (ng/mL) Standard Deviation 43.726 • Interval 1.53 to 155.0	—
Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose Week 12, 1 hour (n=46, 42)	46.84 nanograms per milliliter (ng/mL) Standard Deviation 20.365 • Interval 6.15 to 95.9	82.08 nanograms per milliliter (ng/mL) Standard Deviation 33.779 • Interval 6.12 to 158.0	—
Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose Week 12, 2 hour (n=44, 42)	36.52 nanograms per milliliter (ng/mL) Standard Deviation 14.810 • Interval 1.38 to 83.1	69.79 nanograms per milliliter (ng/mL) Standard Deviation 23.274 • Interval 24.0 to 134.0	—
Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose Week 26/ET, 0 hours (n=43, 46)	6.183 nanograms per milliliter (ng/mL) Standard Deviation 13.673 • Interval 0.0 to 87.5	9.510 nanograms per milliliter (ng/mL) Standard Deviation 17.115 • Interval 0.0 to 113.0	—
Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose Week 26/ET, 20 minutes (n=45, 48)	40.98 nanograms per milliliter (ng/mL) Standard Deviation 31.713 • Interval 0.0 to 117.0	60.48 nanograms per milliliter (ng/mL) Standard Deviation 51.084 • Interval 0.218 to 167.0	—
Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose Week 26/ET, 40 minutes (n=46, 48)	55.83 nanograms per milliliter (ng/mL) Standard Deviation 44.421 • Interval 0.0 to 285.0	85.66 nanograms per milliliter (ng/mL) Standard Deviation 37.983 • Interval 9.87 to 196.0	—
Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose Week 26/ET, 1 hour (n=45, 48)	52.59 nanograms per milliliter (ng/mL) Standard Deviation 42.291 • Interval 0.0 to 293.0	86.25 nanograms per milliliter (ng/mL) Standard Deviation 30.948 • Interval 11.4 to 187.0	—
Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose Week 26/ET, 2 hours (n=44, 48)	39.09 nanograms per milliliter (ng/mL) Standard Deviation 22.606 • Interval 0.0 to 143.0	64.15 nanograms per milliliter (ng/mL) Standard Deviation 23.499 • Interval 21.9 to 150.0	—

Adverse Events

Placebo

Serious events: 7 serious events

Other events: 28 other events

Deaths: 0 deaths

Tofacitinib 5 mg BID

Serious events: 6 serious events

Other events: 40 other events

Deaths: 0 deaths

Tofacitinib 10 mg BID

Serious events: 8 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Placebo n=59 participants at risk Placebo (two placebo tablets) to match tofacitinib for oral administration BID for 26 weeks.	Tofacitinib 5 mg BID n=60 participants at risk Tofacitinib 5 mg (one placebo tablet and one tofacitinib tablet) for oral administration at a dose of 5 mg BID for 26 weeks.	Tofacitinib 10 mg BID n=61 participants at risk Tofacitinib 10 mg (two tofacitinib tablets) for oral administration at a dose of 10 mg BID for 26 weeks.
Blood and lymphatic system disorders Anaemia	1.7% 1/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Crohn's disease	5.1% 3/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	1.7% 1/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Inguinal hernia	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.6% 1/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Intestinal fistula	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.6% 1/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Intestinal obstruction	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.7% 1/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Large intestine perforation	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.7% 1/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Small intestinal obstruction	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.6% 1/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.6% 1/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Cholecystitis acute	1.7% 1/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.7% 1/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.6% 1/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Clostridium difficile colitis	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.7% 1/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Clostridium difficile infection	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.7% 1/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.6% 1/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Rectal abscess	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.7% 1/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Septic shock	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.7% 1/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Intestinal anastomosis complication	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.7% 1/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Nephrolithiasis	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.6% 1/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Surgical and medical procedures Abortion induced	1.7% 1/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	Placebo n=59 participants at risk Placebo (two placebo tablets) to match tofacitinib for oral administration BID for 26 weeks.	Tofacitinib 5 mg BID n=60 participants at risk Tofacitinib 5 mg (one placebo tablet and one tofacitinib tablet) for oral administration at a dose of 5 mg BID for 26 weeks.	Tofacitinib 10 mg BID n=61 participants at risk Tofacitinib 10 mg (two tofacitinib tablets) for oral administration at a dose of 10 mg BID for 26 weeks.
Blood and lymphatic system disorders Anaemia	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	5.0% 3/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	8.2% 5/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	3.4% 2/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 5/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	6.6% 4/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.6% 1/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Crohn's disease	16.9% 10/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	18.3% 11/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	11.5% 7/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	5.0% 3/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	8.2% 5/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	5.1% 3/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.6% 1/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Haemorrhoids	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	1.7% 1/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.7% 1/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Toothache	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Asthenia	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Fatigue	1.7% 1/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.6% 1/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	3.4% 2/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	6.6% 4/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	5.0% 3/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Conjunctivitis	1.7% 1/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	4.9% 3/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	4.9% 3/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	4.9% 3/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Herpes zoster	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	3.4% 2/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 5/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	4.9% 3/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	6.8% 4/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	18.3% 11/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	8.2% 5/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	3.4% 2/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.7% 1/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.6% 1/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	3.4% 2/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.7% 1/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.6% 1/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	6.8% 4/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	10.0% 6/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	13.1% 8/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Vaginal infection	0.00% 0/32 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/30 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	4.2% 1/24 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Vulvovaginal mycotic infection	0.00% 0/32 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/30 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	4.2% 1/24 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Tooth fracture	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 creatinine increased	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 pressure increased	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Lymphocyte count decreased	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.6% 1/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Hyperlipidaemia	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Hypokalaemia	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.7% 1/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	3.4% 2/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	10.0% 6/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	6.6% 4/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	1.7% 1/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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 Torticollis	0.00% 0/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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% 0/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious 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	3.4% 2/59 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	6.7% 4/60 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	3.3% 2/61 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment (30 weeks). Non-SAEs were recorded from time of first dose of study treatment through last participant visit (30 weeks). The same event may appear as both an adverse event (AE) and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.