Clinical Trial Results:
A Multicentre, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study of Oral CP-690, 550 as an Induction Therapy in Subjects With Moderate to Severe Ulcerative Colitis
Summary
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EudraCT number |
2011-004579-35 |
Trial protocol |
GB CZ HU EE DK LV BE ES NL AT DE SK PL HR |
Global end of trial date |
09 Jun 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
15 May 2016
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First version publication date |
15 May 2016
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
A3921095
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01458951 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Pfizer, Inc.
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Sponsor organisation address |
235 E 42nd Street, New York, United States, NY 10017
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Public contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
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Scientific contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
12 Apr 2016
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Jun 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To demonstrate the efficacy of tofacitinib in inducing remission in subjects with moderately to severely active Ulcerative Colitis (UC).
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council on Harmonization (ICH) Good Clinical Practice (GCP)
Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
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Background therapy |
Subjects were permitted to continue stable doses of the following during the study: oral 5-ASA or sulfasalazine, oral corticosteroids up to 25 mg/day prednisone equivalent, and/or chronic antibiotics for UC treatment. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
21 Jun 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Australia: 22
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Country: Number of subjects enrolled |
Austria: 3
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Country: Number of subjects enrolled |
Belgium: 14
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Country: Number of subjects enrolled |
Brazil: 2
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Country: Number of subjects enrolled |
Canada: 17
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Country: Number of subjects enrolled |
Colombia: 3
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Country: Number of subjects enrolled |
Croatia: 2
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Country: Number of subjects enrolled |
Czech Republic: 9
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Country: Number of subjects enrolled |
Denmark: 12
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Country: Number of subjects enrolled |
Estonia: 4
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Country: Number of subjects enrolled |
France: 23
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Country: Number of subjects enrolled |
Germany: 34
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Country: Number of subjects enrolled |
Hungary: 34
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Country: Number of subjects enrolled |
Israel: 6
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Country: Number of subjects enrolled |
Korea, Democratic People's Republic of: 58
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Country: Number of subjects enrolled |
Latvia: 1
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Country: Number of subjects enrolled |
Netherlands: 37
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Country: Number of subjects enrolled |
New Zealand: 17
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Country: Number of subjects enrolled |
Poland: 46
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Country: Number of subjects enrolled |
Romania: 3
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Country: Number of subjects enrolled |
Russian Federation: 17
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Country: Number of subjects enrolled |
Serbia: 6
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Country: Number of subjects enrolled |
Slovakia: 28
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Country: Number of subjects enrolled |
South Africa: 18
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Country: Number of subjects enrolled |
Spain: 4
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Country: Number of subjects enrolled |
Taiwan: 1
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Country: Number of subjects enrolled |
Ukraine: 17
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Country: Number of subjects enrolled |
United Kingdom: 14
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Country: Number of subjects enrolled |
United States: 95
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Worldwide total number of subjects |
547
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EEA total number of subjects |
268
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
517
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From 65 to 84 years |
30
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Subjects were randomized to tofacitinib 10 milligram (mg) or placebo twice a day (BID) (4:1 ratio) after Protocol Amendment 2, which removed tofacitinib 15 mg BID. Due to low subject numbers, tofacitinib 15 mg BID was excluded from efficacy analyses, but was included in subject disposition, baseline characteristics and adverse events analyses. | ||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer, Assessor | ||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Tofacitinib 10 mg BID | ||||||||||||||||||||||||||||||||||||
Arm description |
Subjects received tofacitinib 10 mg tablets orally BID for 9 weeks of double blind treatment period. | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Tofacitinib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received tofacitinib 10 mg BID for 9 weeks of double blind treatment period.
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Arm title
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Tofacitinib 15 mg BID | ||||||||||||||||||||||||||||||||||||
Arm description |
Subjects received tofacitinib 15 mg tablets orally BID for 9 weeks of double blind treatment period. | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Tofacitinib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received tofacitinib 15 mg tablets orally BID for 9 weeks of double blind treatment period.
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Arm title
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Placebo BID | ||||||||||||||||||||||||||||||||||||
Arm description |
Subjects received tofacitinib-matched placebo tablets orally BID for 9 weeks of double blind treatment period. | ||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Tofacitinib-matched placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received tofacitinib matched placebo tablets orally BID for 9 weeks of double blind treatment period.
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Baseline characteristics reporting groups
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Reporting group title |
Tofacitinib 10 mg BID
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Reporting group description |
Subjects received tofacitinib 10 mg tablets orally BID for 9 weeks of double blind treatment period. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Tofacitinib 15 mg BID
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Reporting group description |
Subjects received tofacitinib 15 mg tablets orally BID for 9 weeks of double blind treatment period. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo BID
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Reporting group description |
Subjects received tofacitinib-matched placebo tablets orally BID for 9 weeks of double blind treatment period. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Tofacitinib 10 mg BID
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Reporting group description |
Subjects received tofacitinib 10 mg tablets orally BID for 9 weeks of double blind treatment period. | ||
Reporting group title |
Tofacitinib 15 mg BID
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Reporting group description |
Subjects received tofacitinib 15 mg tablets orally BID for 9 weeks of double blind treatment period. | ||
Reporting group title |
Placebo BID
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Reporting group description |
Subjects received tofacitinib-matched placebo tablets orally BID for 9 weeks of double blind treatment period. |
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End point title |
Percentage of Subjects With Remission at Week 8 [1] | ||||||||||||
End point description |
Remission in subjects was defined by a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point and a rectal bleeding subscore of 0. Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of centrally read flexible proctosigmoidoscopy and physician global assessment (PGA), each graded from 0 to 3 with higher scores indicating more severe disease. These scores were summed up to give a total score range of 0 to 12; where higher score indicating more severe disease. Full analysis set included all subjects who were randomly assigned to either tofacitinib 10 mg BID or placebo BID.
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End point type |
Primary
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End point timeframe |
Week 8
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Notes [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only descriptive data was planned to be reported for this endpoint. |
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Statistical analysis title |
Tofacitinib 10 mg BID vs. Placebo BID at Week 8 | ||||||||||||
Statistical analysis description |
P-value was based on Cochran-Mantel Haenszel (CMH) chi-square test stratified by prior treatment with anti-tumor necrosis factor (TNF), steroid use at baseline and geographic region. Percentage difference and its 95 percent Confidence interval (CI) was based on normal approximation for the difference in binomial proportions. Missing data were imputed using non-responder imputation (NRI).
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Comparison groups |
Tofacitinib 10 mg BID v Placebo BID
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Number of subjects included in analysis |
541
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.0005 | ||||||||||||
Method |
CMH Chi-square Test | ||||||||||||
Parameter type |
Percentage difference | ||||||||||||
Point estimate |
13
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
8.1 | ||||||||||||
upper limit |
17.9 |
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End point title |
Percentage of Subjects Achieving Mucosal Healing at Week 8 [2] | ||||||||||||
End point description |
Mucosal healing in subjects was defined by Mayo endoscopic subscore of 0 or 1. The Mayo endoscopic subscore consisted of the findings of centrally read flexible proctosigmoidoscopy, graded from 0 to 3 with higher scores indicating more severe disease. Full analysis set included all subjects who were randomly assigned to either tofacitinib 10 mg BID or placebo BID.
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End point type |
Secondary
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End point timeframe |
Week 8
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Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only descriptive data was planned to be reported for this endpoint. |
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Statistical analysis title |
Tofacitinib 10 mg BID vs. Placebo BID at Week 8 | ||||||||||||
Statistical analysis description |
P-value was based on CMH chi-square test stratified by prior treatment with anti-TNF, steroid use at baseline and geographic region. Percentage difference and its 95% CI was based on normal approximation for the difference in binomial proportions. Missing data were imputed using NRI.
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Comparison groups |
Tofacitinib 10 mg BID v Placebo BID
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Number of subjects included in analysis |
541
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.0002 | ||||||||||||
Method |
CMH Chi-square Test | ||||||||||||
Parameter type |
Percentage difference | ||||||||||||
Point estimate |
16.8
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
9.5 | ||||||||||||
upper limit |
24.1 |
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End point title |
Percentage of Subjects Achieving Clinical Response at Week 8 [3] | ||||||||||||
End point description |
Clinical response in subjects was defined by a decrease from baseline in Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the rectal bleeding sub score of at least 1 point or an absolute rectal bleeding sub score of 0 or 1. Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible centrally read proctosigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating more severe disease. These scores were summed up to give a total score range of 0 to 12; where higher score indicating more severe disease. Full analysis set included all subjects who were randomly assigned to either tofacitinib 10 mg BID or placebo BID.
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End point type |
Secondary
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End point timeframe |
Week 8
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Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only descriptive data was planned to be reported for this endpoint. |
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Statistical analysis title |
Tofacitinib 10 mg BID vs. Placebo BID at Week 8 | ||||||||||||
Statistical analysis description |
P-value was based on CMH chi-square test stratified by prior treatment with anti-TNF, steroid use at baseline and geographic region. Percentage difference and its 95% CI was based on normal approximation for the difference in binomial proportions. Missing data were imputed using NRI.
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Comparison groups |
Tofacitinib 10 mg BID v Placebo BID
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Number of subjects included in analysis |
541
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
CMH Chi-square Test | ||||||||||||
Parameter type |
Percentage difference | ||||||||||||
Point estimate |
26.4
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
16.8 | ||||||||||||
upper limit |
36 |
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End point title |
Percentage of Subjects With Endoscopic Remission at Week 8 [4] | ||||||||||||
End point description |
Endoscopic remission in subjects was defined by Mayo endoscopic subscore of 0. The Mayo endoscopic subscore consisted of the findings of centrally read flexible proctosigmoidoscopy, graded from 0 to 3 with higher scores indicating more severe disease. Full analysis set included all subjects who were randomly assigned to either tofacitinib 10 mg BID or placebo BID.
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End point type |
Secondary
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End point timeframe |
Week 8
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Notes [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only descriptive data was planned to be reported for this endpoint. |
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Statistical analysis title |
Tofacitinib 10 mg BID vs. Placebo BID at Week 8 | ||||||||||||
Statistical analysis description |
P-value was based on CMH chi-square test stratified by prior treatment with anti-TNF, steroid use at baseline and geographic region. Percentage difference and its 95% CI was based on normal approximation for the difference in binomial proportions. Missing data were imputed using NRI.
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Comparison groups |
Tofacitinib 10 mg BID v Placebo BID
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Number of subjects included in analysis |
541
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.0425 | ||||||||||||
Method |
CMH Chi-square Test | ||||||||||||
Parameter type |
Percentage difference | ||||||||||||
Point estimate |
5.2
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
1.8 | ||||||||||||
upper limit |
8.6 |
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End point title |
Percentage of Subjects With Clinical Remission at Week 8 [5] | ||||||||||||
End point description |
Clinical remission in subjects was defined by a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point. Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible centrally read proctosigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating more severe disease. These scores were summed up to give a total score range of 0 to 12; where higher score indicating more severe disease. Full analysis set included all subjects who were randomly assigned to either tofacitinib 10 mg BID or placebo BID.
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End point type |
Secondary
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End point timeframe |
Week 8
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Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only descriptive data was planned to be reported for this endpoint. |
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Statistical analysis title |
Tofacitinib 10 mg BID vs. Placebo BID at Week 8 | ||||||||||||
Statistical analysis description |
P-value was based on CMH chi-square test stratified by prior treatment with anti-TNF, steroid use at baseline and geographic region. Percentage difference and its 95% CI was based on normal approximation for the difference in binomial proportions. Missing data were imputed using NRI.
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Comparison groups |
Tofacitinib 10 mg BID v Placebo BID
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Number of subjects included in analysis |
541
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.0004 | ||||||||||||
Method |
CMH Chi-square Test | ||||||||||||
Parameter type |
Percentage difference | ||||||||||||
Point estimate |
13.2
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Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
8.3 | ||||||||||||
upper limit |
18.1 |
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End point title |
Percentage of Subjects With Symptomatic Remission at Week 8 [6] | ||||||||||||
End point description |
Symptomatic remission was defined by a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point, and 0 subscore for both rectal bleeding and stool frequency. Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible centrally read proctosigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating more severe disease. These scores were summed up to give a total score range of 0 to 12; where higher score indicated more severe disease. Full analysis set indicating all subjects who were randomly assigned to either tofacitinib 10 mg BID or placebo BID.
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End point type |
Secondary
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End point timeframe |
Week 8
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Notes [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only descriptive data was planned to be reported for this endpoint. |
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Statistical analysis title |
Tofacitinib 10 mg BID vs. Placebo BID at Week 8 | ||||||||||||
Statistical analysis description |
P-value was based on CMH chi-square test stratified by prior treatment with anti-TNF, steroid use at baseline and geographic region. Percentage difference and its 95% CI was based on normal approximation for the difference in binomial proportions. Missing data were imputed using NRI.
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Comparison groups |
Tofacitinib 10 mg BID v Placebo BID
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Number of subjects included in analysis |
541
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.009 | ||||||||||||
Method |
CMH Chi-square Test | ||||||||||||
Parameter type |
Percentage difference | ||||||||||||
Point estimate |
8
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
3.9 | ||||||||||||
upper limit |
12.2 |
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End point title |
Percentage of Subjects With Deep Remission at Week 8 [7] | ||||||||||||
End point description |
Deep remission in subjects was defined by a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point and 0 subscore for both rectal bleeding and endoscopic subscores. Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible centrally read proctosigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating more severe disease. These scores were summed up to give a total score range of 0 to 12; where higher score indicating more severe disease. Full analysis set included all subjects who were randomly assigned to either tofacitinib 10 mg BID or placebo BID.
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End point type |
Secondary
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End point timeframe |
Week 8
|
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Notes [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only descriptive data was planned to be reported for this endpoint. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Tofacitinib 10 mg BID vs. Placebo BID at Week 8 | ||||||||||||
Statistical analysis description |
P-value was based on CMH chi-square test stratified by prior treatment with anti-TNF, steroid use at baseline and geographic region. Percentage difference and its 95% CI was based on normal approximation for the difference in binomial proportions. Missing data were imputed using NRI.
|
||||||||||||
Comparison groups |
Tofacitinib 10 mg BID v Placebo BID
|
||||||||||||
Number of subjects included in analysis |
541
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.1408 | ||||||||||||
Method |
CMH Chi-square Test | ||||||||||||
Parameter type |
Percentage difference | ||||||||||||
Point estimate |
3.3
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.1 | ||||||||||||
upper limit |
6.6 |
|
|||||||||||||||||||||||||
End point title |
Partial Mayo Scores [8] | ||||||||||||||||||||||||
End point description |
A partial mayo score (mayo score without endoscopy) ranges from 0 (normal or inactive disease) to 9 (severe disease) and calculated as the sum of 3 subscores (stool frequency, rectal bleeding and PGA) and each grading from 0 to 3 with higher scores indicating more severe disease. Full analysis set included all subjects who were randomly assigned to either tofacitinib 10 mg BID or placebo BID. Here, ‘n’ signifies those subjects who were evaluable at specified time point for each arm, respectively.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 2, 4, 8
|
||||||||||||||||||||||||
Notes [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only descriptive data was planned to be reported for this endpoint. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Change From Baseline in Partial Mayo Scores at Weeks 2, 4 and 8 [9] | |||||||||||||||||||||
End point description |
Change in Partial Mayo scores at Weeks 2, 4, 8 relative to baseline were reported. A Partial Mayo Score (Mayo score without endoscopy) ranges from 0 (normal or inactive disease) to 9 (severe disease) and calculated as the sum of 3 subscores (stool frequency, rectal bleeding and PGA) with each graded from 0 to 3 with higher scores indicating more severe disease. Full analysis set included all subjects who were randomly assigned to either tofacitinib 10 mg BID or placebo BID. Here, ‘n’ signifies those subjects who were evaluable at specified time point for each arm, respectively.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline, Weeks 2, 4, 8
|
|||||||||||||||||||||
Notes [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only descriptive data was planned to be reported for this endpoint. |
||||||||||||||||||||||
|
||||||||||||||||||||||
Statistical analysis title |
Tofacitinib 10 mg BID vs. Placebo BID at Week 2 | |||||||||||||||||||||
Statistical analysis description |
The change from baseline was analyzed using mixed effect model with treatment group, prior treatment with antiTNF, steroid use at baseline, geographic region, visit and visit by treatment group all as fixed effects, and subjects as a random effect.
|
|||||||||||||||||||||
Comparison groups |
Tofacitinib 10 mg BID v Placebo BID
|
|||||||||||||||||||||
Number of subjects included in analysis |
541
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||
P-value |
< 0.0001 | |||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||
Parameter type |
Least square mean difference | |||||||||||||||||||||
Point estimate |
-1
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-1.4 | |||||||||||||||||||||
upper limit |
-0.6 | |||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||||||||
Dispersion value |
0.2
|
|||||||||||||||||||||
Statistical analysis title |
Tofacitinib 10 mg BID vs. Placebo BID at Week 4 | |||||||||||||||||||||
Statistical analysis description |
The change from baseline was analyzed using mixed effect model with treatment group, prior treatment with antiTNF, steroid use at baseline, geographic region, visit and visit by treatment group all as fixed effects, and subjects as a random effect.
|
|||||||||||||||||||||
Comparison groups |
Tofacitinib 10 mg BID v Placebo BID
|
|||||||||||||||||||||
Number of subjects included in analysis |
541
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||
P-value |
< 0.0001 | |||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||
Parameter type |
Least square mean difference | |||||||||||||||||||||
Point estimate |
-1.2
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-1.6 | |||||||||||||||||||||
upper limit |
-0.7 | |||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||||||||
Dispersion value |
0.2
|
|||||||||||||||||||||
Statistical analysis title |
Tofacitinib 10 mg BID vs. Placebo BID at Week 8 | |||||||||||||||||||||
Statistical analysis description |
The change from baseline was analyzed using mixed effect model with treatment group, prior treatment with antiTNF, steroid use at baseline, geographic region, visit and visit by treatment group all as fixed effects, and subjects as a random effect.
|
|||||||||||||||||||||
Comparison groups |
Tofacitinib 10 mg BID v Placebo BID
|
|||||||||||||||||||||
Number of subjects included in analysis |
541
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||
P-value |
< 0.0001 | |||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||
Parameter type |
Least square mean difference | |||||||||||||||||||||
Point estimate |
-1.3
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-1.7 | |||||||||||||||||||||
upper limit |
-0.9 | |||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||||||||
Dispersion value |
0.2
|
|
|||||||||||||||||||
End point title |
Change From Baseline in Total Mayo Score at Week 8 [10] | ||||||||||||||||||
End point description |
Change in total Mayo score at Week 8 relative to baseline was reported. Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible centrally read proctosigmoidoscopy and PGA, each graded from 0 to 3 with higher scores indicating more severe disease. These scores were summed up to give a total score range of 0 to 12; where higher score indicating more severe disease. Full analysis set included all subjects who were randomly assigned to either tofacitinib 10 mg BID or placebo BID. Here, ‘n’ signifies those subjects who were evaluable at specified time point for each arm, respectively.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, Week 8
|
||||||||||||||||||
Notes [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only descriptive data was planned to be reported for this endpoint. |
|||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
Tofacitinib 10 mg BID vs. Placebo BID at Week 8 | ||||||||||||||||||
Statistical analysis description |
The change from baseline at Week 8 was analyzed using an analysis of covariance (ANCOVA) model with treatment group, prior treatment with anti-TNF, steroid use at baseline and geographic region as factors and baseline as a covariate based on the observed-case data.
|
||||||||||||||||||
Comparison groups |
Tofacitinib 10 mg BID v Placebo BID
|
||||||||||||||||||
Number of subjects included in analysis |
541
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
|||||||||||||||||||
P-value |
< 0.0001 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
Least Square Mean Difference | ||||||||||||||||||
Point estimate |
-1.6
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-2.2 | ||||||||||||||||||
upper limit |
-1 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||
Dispersion value |
0.3
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Baseline up to Day 98
|
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Adverse event reporting additional description |
The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non serious event during the study.
|
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Tofacitinib 10 mg BID
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received tofacitinib 10 mg tablets orally BID for 9 weeks of double blind treatment period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo BID
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received tofacitinib-matched placebo tablets orally BID for 9 weeks of double blind treatment period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Tofacitinib 15 mg BID
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received tofacitinib 15 mg tablets orally BID for 9 weeks of double blind treatment period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
30 Nov 2012 |
Tofacitinib 15 mg BID arm was removed. Prior to this, subjects were randomized to tofacitinib 10 mg BID, tofacitinib 15 mg BID, or placebo BID (2:2:1 ratio). |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |