A Study To Assess The Efficacy And Safety Of PF-04236921 In Subjects With Crohn's Disease Who Failed Anti-TNF Therapy

CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response at Week 12 were compared between placebo and PF-04236921 200 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 3, that will yield different estimates for placebo for the two different models.

Time frame: Baseline and Week 12

Population: The analysis was performed on FAS 200 mg vs placebo. The 200 mg arm was halted before reaching the planned sample size of approximately 60 and was no longer powered at the planned level to test against placebo. Thus, the 200 mg vs placebo comparison is a sensitivity analysis.

CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response at Week 12 were compared between placebo and and PF-04236921 10 mg/50 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).

Time frame: Baseline and Week 12

Population: Primary analysis: FAS excluding 200 mg arm (halted prematurely before reaching the planned sample size and thus no longer powered at the planned level to test against placebo).

CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response at Week 8 were compared between placebo and PF-04236921 200 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 1, that will yield different estimates for placebo for the two different models.

Time frame: Baseline and Week 8

Population: The analysis was performed on FAS participants of the 200 mg and placebo arms, referred to as FAS 200 mg versus (vs) placebo. The 200 mg arm was halted before reaching the planned sample size of approximately 60 and was no longer powered at the planned level to test against placebo. Thus, the 200 mg vs placebo comparison is a sensitivity analysis.

CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response at Week 8 were compared between placebo and PF-04236921 10 mg/50 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score greater than or equal to (\>=) 0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).

Time frame: Baseline and Week 8

Population: Primary analysis: full analysis set (FAS, defined as all randomized participants who received at least 1 dose of study treatment; 2 participants \[10 mg arm\] excluded due to a quality issue) excluding 200 mg (halted prematurely before reaching the planned sample size and thus no longer powered at the planned level to test against placebo).

CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit, and higher score indicate more severe disease. The Outcome included a Linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 11, that will yield different estimates for placebo for the two different models.

Time frame: Baseline and Weeks 2, 4, 6, 8, 10, and 12

Population: The analysis was performed on the FAS 200 mg vs placebo. The 200 mg arm was halted before reaching the planned sample size of approximately 60 participants. n signifies the number of subjects with observed data of each arm at each time point.

CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit, and higher score indicate more severe disease. The Outcome included a Linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).

Time frame: Baseline and Weeks 2, 4, 6, 8, 10, and 12

Population: The analysis was performed on the FAS excluding 200 mg arm (which was halted prematurely). n signifies the number of subjects with observed data of each arm at each time point.

An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. Treatment-emergent were events between first dose of treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

Time frame: Induction period: from Week 0 (Day 1) through Week 12; follow-up period: from Week 12 (or discontinuation from the induction period) through last subject visit (up to 28 weeks after completion of or discontinuation from the 12-week induction period)

Population: The SAS consisted of all participants who received at least 1 dose of study drug. n signifies number of participants with observed data at the time point of each arm. From Weeks 16 to 40, only participants who remained in the follow-up period of this study and did not enter NCT01405196 were analyzed.

The percentage of participants with confirmed positive ADA was summarized for each treatment arm. ADA positive was defined as ADA titer defined as ADA titer (ie, the reciprocal of the highest dilution that gives a value equivalent to the cut point of the assay) \>= 4.32.

Time frame: At baseline (Day 1) and at Weeks 4, 8, 12, 16, 24, 32 and 40

Population: The SAS consisted of all participants who received at least 1 dose of study drug. n signifies number of participants with observed data at the time point of each arm. From Weeks 16 to 40, only participants who remained in the follow-up period of this study and did not enter NCT01405196 were analyzed.

The percentage of participants with confirmed positive NAbs was summarized for each treatment arm. Only ADA positive samples were analyzed for Nab. A multi-tiered approach was utilized to detect NAbs. NAb serum samples were screened at tier one, and those found presumptively NAb positive was further tested with the confirmatory assay (tier two). The percentage of subjects with confirmed positive NAbs was summarized for each treatment.

Time frame: At baseline (Day 1) and at Weeks 4, 8, 12, 16, 24, 32 and 40

Population: The SAS consisted of all participants who received at least 1 dose of study drug. n signifies number of participants with observed data at the time point of each arm. From Weeks 16 to 40, only participants who remained in the follow-up period of this study and did not enter NCT01405196 were analyzed.

Time frame: Day 1 (predose), and at Weeks 2, 4 (Day 28, predose), 8, 10, 12, 16, 20, 24, 28, 32, 36, and 40

Population: The pharmacokinetic (PK) analysis set was the subset of participants from the SAS who provided at least 1 PK concentration (2 participants \[10 mg arm\] excluded due to a quality issue). n is the number of participants with PK data at the visit. From Weeks 16 to 40, only participants who remained in the follow-up period of this study were analyzed.

CDAI-100 response was defined as a decrease in CDAI score of 100 or greater from baseline. The proportions of participants with CDAI-100 response at Week 12 were compared between placebo and PF-04236921 200 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 9, that will yield different estimates for placebo for the two different models.

Time frame: Baseline and Weeks 2, 4, 6, 8, 10, and 12

Population: The analysis was performed on the FAS 200 mg vs placebo. The 200 mg arm was halted before reaching the planned sample size of approximately 60 participants. n signifies the number of subjects with observed data of each arm at each time point.

CDAI-100 response was defined as a decrease in CDAI score of 100 or greater from baseline. The proportions of participants with CDAI-100 response at Week 12 were compared between placebo and PF-04236921 10 mg/50 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).

Time frame: Baseline and Weeks 2, 4, 6, 8, 10, and 12

Population: The analysis was performed on the FAS excluding 200 mg arm (which was halted prematurely). n signifies the number of subjects with observed data of each arm at each time point.

CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response were compared between placebo and PF-04236921 200 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 5, that will yield different estimates for placebo for the two different models.

Time frame: Baseline and Weeks 2, 4, 6, and 10

Population: The analysis was performed on the FAS 200 mg vs placebo. The 200 mg arm was halted before reaching the planned sample size of approximately 60 participants. n signifies the number of subjects with observed data of each arm at each time point.

CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response were compared between placebo and PF-04236921 10 mg/50 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).

Time frame: Baseline and Weeks 2, 4, 6, and 10

Population: The analysis was performed on the FAS excluding 200 mg arm (which was halted prematurely). n signifies the number of subjects with observed data of each arm at each time point.

CDAI remission rate was defined as an absolute CDAI score \<150. The proportions of participants with CDAI remission were compared between placebo and PF-04236921 200 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 7, that will yield different estimates for placebo for the two different models.

Time frame: Baseline and Weeks 2, 4, 6, 8, 10, and 12

Population: The analysis was performed on the FAS 200 mg vs placebo. The 200 mg arm was halted before reaching the planned sample size of approximately 60 participants. n signifies the number of subjects with observed data of each arm at each time point.

CDAI remission rate was defined as an absolute CDAI score less than (\<) 150. The proportions of participants with CDAI remission were compared between placebo and PF-04236921 10 mg/50 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score \>=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).

Time frame: Baseline and Weeks 2, 4, 6, 8, 10, and 12

Population: The analysis was performed on the FAS excluding 200 mg arm (which was halted prematurely). n signifies the number of subjects with observed data of each arm at each time point.