Study To Test Whether PF-00547659 Is Safe And Improves Disease Symptoms In Patients With Crohn's Disease

A Double-blind, Randomized, Placebo-controlled, Dose-ranging Study To Evaluate The Efficacy And Safety Of Pf-00547659 In Subjects With Crohn's Disease (Opera)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01276509

Acronym

OPERA

Enrollment

265

Registered

2011-01-13

Start date

2011-04-06

Completion date

2015-10-09

Last updated

2021-06-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Crohn's Disease

Keywords

Crohn's disease Safety Efficacy Pharmacokinetics Pharmacodynamics Crohn's Disease Activity Index (CDAI)

Brief summary

Adults with Crohn's disease that is clinically active despite conventional treatment will be eligible for this study. Patients may receive one of three doses of PF-00547659 (experimental drug) or placebo (inactive drug). Disease activity will be measured every two weeks.

Interventions

DRUGPF-00547659 SC injection

Placebo delivered SC, 3 doses separated by 4 weeks

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

* Subjects must have failed or are intolerant to anti-TNFs and/or immunosuppressants (AZA, 6-MP, and/or MTX). * hsCRP greater than 3mg/L * Ulcerations demonstrated by colonoscopy performed during screening or 8 weeks prior to screening

Exclusion criteria

* Pregnant or breast feeding * Short bowel syndrome due to multiple small bowel resections * Presence of a stoma

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Crohn's Disease Activity Index (CDAI) 70 Response Rate	Week 8 and week 12	Crohn's Disease Activity Index (CDAI) is a number which consists of information collected from a 7-day diary from the participants regarding symptoms. Remission is considered a score of 150 or less. Active disease is considered 200 or greater. A response to therapy is considered a decline in CDAI score of 70-points from baseline. CDAI response rate at week 8 and week 12 was measured between the investigational product group and the placebo group.

Secondary

Measure	Time frame	Description
Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Week 0-12	Number of participants with adverse events (AEs), withdrawals due to AEs and Serious AEs (SAEs) were reported.
Number of Adverse Events (AEs) - PF-00547659 Dose Levels Versus Placebo	Week 0-12	Number of adverse events (all causalities and treatment related) was reported between the investigational product groups and the placebo group.
Percentage of Participants With a Crohn's Disease Activity Index (CDAI) Remission	Weeks 8 and week 12	Percentage of participants with a CDAI remission (defined as a CDAI reduction to \<150 points).
Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 2, 4, 6, 8, 10 and 12	Percentage of participants with Crohn's Disease Activity Index (CDAI)-70 response were reported.
Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 2, 4, 6, 8, 10 and 12	Percentage of participants with Crohn's Disease Activity Index (CDAI)-100 response were reported.
Immunogenicity Assessment of Anti-drug Antibodies (ADAs)	Day 1, Week 4, Week 8, Week 12, Week 20, Week 28, Week 36	Confirmed cumulative incidence of anti-drug antibodies development to PF-00547659
The Pharmacokinetics (PK) of Total PF-00547659 - Area Under the Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf)	Day 1, 14, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224 and 252	The Pharmacokinetics (PK) of total PF-00547659 was characterized using a population PK approach. PK parameters including but not limited to area under the concentration-time profile (AUC), clearance (CL) and half life were estimated using data pooled from both typical and additional PK groups. AUCinf is area under the concentration time profile from time zero extrapolated to infinite time.
The Pharmacokinetics (PK) of Total PF-00547659 - Area Under the Concentration Time Profile From Time Zero to Time Tau (AUCtau)	Day 1, 14, and 28	The Pharmacokinetics (PK) of total PF-00547659 was characterized using a population PK approach. PK parameters including but not limited to AUC, CL and half life were estimated using data pooled from both typical and additional PK groups. AUCtau is area under the concentration time profile from time zero to time tau, the dosing interval, where tau = 672 hours (4 weeks)
The Pharmacokinetics (PK) of Total PF-00547659 - Maximum Observed Concentration (Cmax)	Day 1, 14, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224 and 252	The Pharmacokinetics (PK) of total PF-00547659 was characterized using a population PK approach. PK parameters including but not limited to AUC, CL and half life were estimated using data pooled from both typical and additional PK groups. Cmax is maximum observed concentration.
The Pharmacokinetics (PK) of Total PF-00547659 - Time for Cmax (Tmax)	Day 1, 14, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224 and 252	The Pharmacokinetics (PK) of total PF-00547659 was characterized using a population PK approach. PK parameters including but not limited to AUC, CL and half life were estimated using data pooled from both typical and additional PK groups. Tmax is time for Cmax.
The Pharmacokinetics (PK) of Total PF-00547659 - Terminal Half Life (Thalf)	Day 1, 14, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224 and 252	The Pharmacokinetics (PK) of total PF-00547659 was characterized using a population PK approach. PK parameters including but not limited to AUC, CL and half life were estimated using data pooled from both typical and additional PK groups. Thalf is terminal half life.
The Pharmacokinetics (PK) of Total PF-00547659 - Apparent Clearance (CL/F)	Day 1, 14, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224 and 252	The Pharmacokinetics (PK) of total PF-00547659 was characterized using a population PK approach. PK parameters including but not limited to AUC, CL and half life were estimated using data pooled from both typical and additional PK groups. CL/F is apparent clearance.

Countries

Austria, Belgium, Bulgaria, Canada, France, Germany, Japan, Netherlands, Norway, Poland, Serbia, Slovakia, South Africa, South Korea, Spain, United States

Participant flow

Pre-assignment details

In total, 265 participants were randomized and 262 entered the study and received study treatment.

Participants by arm

Arm	Count
PF-00547659 22.5 mg PF-00547659 22.5 mg delivered subcutaneously (SC), 3 doses separated by 4 weeks.	66
PF-00547659 75 mg PF-00547659 75 mg delivered SC, 3 doses separated by 4 weeks	65
PF-00547659 225 mg PF-00547659 225 mg delivered SC, 3 doses separated by 4 weeks	68
Placebo Placebo delivered SC, 3 doses separated by 4 weeks.	63
Total	262

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Adverse Event	9	8	4	3
Overall Study	Lack of Efficacy	2	1	1	2
Overall Study	Other	0	1	0	0
Overall Study	Pregnancy	1	0	0	0
Overall Study	Withdrawal by Subject	1	2	0	0

Baseline characteristics

Characteristic	PF-00547659 22.5 mg	PF-00547659 75 mg	PF-00547659 225 mg	Placebo	Total
Age, Continuous	37.3 years STANDARD_DEVIATION 13	34.4 years STANDARD_DEVIATION 10.7	35.9 years STANDARD_DEVIATION 11	34.4 years STANDARD_DEVIATION 11.1	35.5 years STANDARD_DEVIATION 11.5
Sex: Female, Male Female	48 Participants	35 Participants	43 Participants	30 Participants	156 Participants
Sex: Female, Male Male	18 Participants	30 Participants	25 Participants	33 Participants	106 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	36 / 66	32 / 65	42 / 68	35 / 63
serious Total, serious adverse events	12 / 66	11 / 65	11 / 68	6 / 63

Outcome results

Primary

Percentage of Participants With Crohn's Disease Activity Index (CDAI) 70 Response Rate

Crohn's Disease Activity Index (CDAI) is a number which consists of information collected from a 7-day diary from the participants regarding symptoms. Remission is considered a score of 150 or less. Active disease is considered 200 or greater. A response to therapy is considered a decline in CDAI score of 70-points from baseline. CDAI response rate at week 8 and week 12 was measured between the investigational product group and the placebo group.

Time frame: Week 8 and week 12

Population: The full analysis set included all randomized participants who received at least one dose of study medication.

Arm	Measure	Group	Value (NUMBER)
PF-00547659 22.5 mg	Percentage of Participants With Crohn's Disease Activity Index (CDAI) 70 Response Rate	Week 8 (n =50, 55, 62, 56)	52.7 Percentage of Participants
PF-00547659 22.5 mg	Percentage of Participants With Crohn's Disease Activity Index (CDAI) 70 Response Rate	Week 12 (n = 51, 49, 61, 54)	62.0 Percentage of Participants
PF-00547659 75 mg	Percentage of Participants With Crohn's Disease Activity Index (CDAI) 70 Response Rate	Week 12 (n = 51, 49, 61, 54)	64.7 Percentage of Participants
PF-00547659 75 mg	Percentage of Participants With Crohn's Disease Activity Index (CDAI) 70 Response Rate	Week 8 (n =50, 55, 62, 56)	60.1 Percentage of Participants
PF-00547659 225 mg	Percentage of Participants With Crohn's Disease Activity Index (CDAI) 70 Response Rate	Week 8 (n =50, 55, 62, 56)	62.7 Percentage of Participants
PF-00547659 225 mg	Percentage of Participants With Crohn's Disease Activity Index (CDAI) 70 Response Rate	Week 12 (n = 51, 49, 61, 54)	57.5 Percentage of Participants
Placebo	Percentage of Participants With Crohn's Disease Activity Index (CDAI) 70 Response Rate	Week 8 (n =50, 55, 62, 56)	47.7 Percentage of Participants
Placebo	Percentage of Participants With Crohn's Disease Activity Index (CDAI) 70 Response Rate	Week 12 (n = 51, 49, 61, 54)	58.6 Percentage of Participants

Comparison: Difference from placebo at Week 8p-value: 0.339390% CI: [-0.149, 0.249]Mixed Models Analysis

Comparison: Difference from placebo at Week 8p-value: 0.143390% CI: [-0.068, 0.316]Mixed Models Analysis

Comparison: Difference from placebo at Week 8p-value: 0.092290% CI: [-0.036, 0.335]Mixed Models Analysis

Comparison: Difference from placebo at Week 12p-value: 0.386490% CI: [-0.158, 0.225]Mixed Models Analysis

Comparison: Difference from placebo at Week 12p-value: 0.300590% CI: [-0.131, 0.253]Mixed Models Analysis

Comparison: Difference from placebo at Week 12p-value: 0.538590% CI: [-0.198, 0.176]Mixed Models Analysis

Secondary

Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer

Percentage of participants with Crohn's Disease Activity Index (CDAI)-100 response were reported.

Time frame: Week 2, 4, 6, 8, 10 and 12

Population: The full analysis set included all randomized participants who received at least one dose of study medication.

Arm	Measure	Group	Value (NUMBER)
PF-00547659 22.5 mg	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 2 (n = 64, 60, 63, 60)	19.3 Percentage of Participants
PF-00547659 22.5 mg	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 4 (n = 58, 60 ,65, 58)	29.2 Percentage of Participants
PF-00547659 22.5 mg	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 6 (n =56, 54, 64, 58)	40.6 Percentage of Participants
PF-00547659 22.5 mg	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 8 (n = 50, 55, 62, 56)	50.5 Percentage of Participants
PF-00547659 22.5 mg	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 10 (n = 50, 48, 62, 52)	53.2 Percentage of Participants
PF-00547659 22.5 mg	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 12 (n = 51, 49, 61, 54)	56.0 Percentage of Participants
PF-00547659 75 mg	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 12 (n = 51, 49, 61, 54)	47.7 Percentage of Participants
PF-00547659 75 mg	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 8 (n = 50, 55, 62, 56)	48.3 Percentage of Participants
PF-00547659 75 mg	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 2 (n = 64, 60, 63, 60)	18.4 Percentage of Participants
PF-00547659 75 mg	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 6 (n =56, 54, 64, 58)	42.6 Percentage of Participants
PF-00547659 75 mg	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 4 (n = 58, 60 ,65, 58)	32.3 Percentage of Participants
PF-00547659 75 mg	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 10 (n = 50, 48, 62, 52)	47.4 Percentage of Participants
PF-00547659 225 mg	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 4 (n = 58, 60 ,65, 58)	28.2 Percentage of Participants
PF-00547659 225 mg	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 6 (n =56, 54, 64, 58)	40.4 Percentage of Participants
PF-00547659 225 mg	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 8 (n = 50, 55, 62, 56)	57.0 Percentage of Participants
PF-00547659 225 mg	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 12 (n = 51, 49, 61, 54)	53.8 Percentage of Participants
PF-00547659 225 mg	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 10 (n = 50, 48, 62, 52)	50.9 Percentage of Participants
PF-00547659 225 mg	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 2 (n = 64, 60, 63, 60)	20.0 Percentage of Participants
Placebo	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 10 (n = 50, 48, 62, 52)	43.6 Percentage of Participants
Placebo	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 12 (n = 51, 49, 61, 54)	44.4 Percentage of Participants
Placebo	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 4 (n = 58, 60 ,65, 58)	29.5 Percentage of Participants
Placebo	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 8 (n = 50, 55, 62, 56)	41.4 Percentage of Participants
Placebo	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 2 (n = 64, 60, 63, 60)	18.5 Percentage of Participants
Placebo	Crohn's Disease Activity Index (CDAI) -100 Response Rates Over Timer	Week 6 (n =56, 54, 64, 58)	39.3 Percentage of Participants

Secondary

Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time

Percentage of participants with Crohn's Disease Activity Index (CDAI)-70 response were reported.

Time frame: Week 2, 4, 6, 8, 10 and 12

Population: The full analysis set included all randomized participants who received at least one dose of study medication.

Arm	Measure	Group	Value (NUMBER)
PF-00547659 22.5 mg	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 2 (n = 64, 60, 63, 60)	35.1 Percentage of Participants
PF-00547659 22.5 mg	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 4 (n = 58, 60, 65, 58)	38.0 Percentage of Participants
PF-00547659 22.5 mg	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 6 (n =56, 54, 64, 58)	45.3 Percentage of Participants
PF-00547659 22.5 mg	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 8 (n =50, 55, 62, 56)	52.7 Percentage of Participants
PF-00547659 22.5 mg	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 10 (n =50, 48, 60, 52)	67.4 Percentage of Participants
PF-00547659 22.5 mg	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 12 (n = 51, 49, 61, 54)	62.0 Percentage of Participants
PF-00547659 75 mg	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 12 (n = 51, 49, 61, 54)	64.7 Percentage of Participants
PF-00547659 75 mg	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 8 (n =50, 55, 62, 56)	60.1 Percentage of Participants
PF-00547659 75 mg	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 2 (n = 64, 60, 63, 60)	22.4 Percentage of Participants
PF-00547659 75 mg	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 6 (n =56, 54, 64, 58)	53.4 Percentage of Participants
PF-00547659 75 mg	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 4 (n = 58, 60, 65, 58)	39.5 Percentage of Participants
PF-00547659 75 mg	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 10 (n =50, 48, 60, 52)	58.2 Percentage of Participants
PF-00547659 225 mg	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 4 (n = 58, 60, 65, 58)	36.2 Percentage of Participants
PF-00547659 225 mg	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 6 (n =56, 54, 64, 58)	47.5 Percentage of Participants
PF-00547659 225 mg	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 8 (n =50, 55, 62, 56)	62.7 Percentage of Participants
PF-00547659 225 mg	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 12 (n = 51, 49, 61, 54)	57.5 Percentage of Participants
PF-00547659 225 mg	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 10 (n =50, 48, 60, 52)	61.6 Percentage of Participants
PF-00547659 225 mg	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 2 (n = 64, 60, 63, 60)	33.8 Percentage of Participants
Placebo	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 10 (n =50, 48, 60, 52)	53.0 Percentage of Participants
Placebo	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 12 (n = 51, 49, 61, 54)	58.6 Percentage of Participants
Placebo	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 4 (n = 58, 60, 65, 58)	38.3 Percentage of Participants
Placebo	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 8 (n =50, 55, 62, 56)	47.7 Percentage of Participants
Placebo	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 2 (n = 64, 60, 63, 60)	35.5 Percentage of Participants
Placebo	Crohn's Disease Activity Index (CDAI)-70 Response Rates Over Time	Week 6 (n =56, 54, 64, 58)	48.0 Percentage of Participants

Secondary

Immunogenicity Assessment of Anti-drug Antibodies (ADAs)

Confirmed cumulative incidence of anti-drug antibodies development to PF-00547659

Time frame: Day 1, Week 4, Week 8, Week 12, Week 20, Week 28, Week 36

Population: The safety analysis set included all participants who receive at least 1 dose of PF-00547659. Participants in placebo arm were not included in this analysis.

Arm	Measure	Group	Value (NUMBER)
PF-00547659 22.5 mg	Immunogenicity Assessment of Anti-drug Antibodies (ADAs)	Week 28 (n = 8, 1, 1)	1 events
PF-00547659 22.5 mg	Immunogenicity Assessment of Anti-drug Antibodies (ADAs)	Week 4 (n = 55, 52, 55)	2 events
PF-00547659 22.5 mg	Immunogenicity Assessment of Anti-drug Antibodies (ADAs)	Week 36 (n = 6, 2, 1)	0 events
PF-00547659 22.5 mg	Immunogenicity Assessment of Anti-drug Antibodies (ADAs)	Day 1 (n =46, 52, 53)	3 events
PF-00547659 22.5 mg	Immunogenicity Assessment of Anti-drug Antibodies (ADAs)	Week 8 (n = 44, 47, 56)	1 events
PF-00547659 22.5 mg	Immunogenicity Assessment of Anti-drug Antibodies (ADAs)	Week 12 (n = 47, 51, 51)	3 events
PF-00547659 22.5 mg	Immunogenicity Assessment of Anti-drug Antibodies (ADAs)	Week 20 (n = 4, 3, 1)	0 events
PF-00547659 75 mg	Immunogenicity Assessment of Anti-drug Antibodies (ADAs)	Day 1 (n =46, 52, 53)	5 events
PF-00547659 75 mg	Immunogenicity Assessment of Anti-drug Antibodies (ADAs)	Week 20 (n = 4, 3, 1)	0 events
PF-00547659 75 mg	Immunogenicity Assessment of Anti-drug Antibodies (ADAs)	Week 28 (n = 8, 1, 1)	0 events
PF-00547659 75 mg	Immunogenicity Assessment of Anti-drug Antibodies (ADAs)	Week 12 (n = 47, 51, 51)	5 events
PF-00547659 75 mg	Immunogenicity Assessment of Anti-drug Antibodies (ADAs)	Week 8 (n = 44, 47, 56)	1 events
PF-00547659 75 mg	Immunogenicity Assessment of Anti-drug Antibodies (ADAs)	Week 36 (n = 6, 2, 1)	0 events
PF-00547659 75 mg	Immunogenicity Assessment of Anti-drug Antibodies (ADAs)	Week 4 (n = 55, 52, 55)	4 events
PF-00547659 225 mg	Immunogenicity Assessment of Anti-drug Antibodies (ADAs)	Week 36 (n = 6, 2, 1)	0 events
PF-00547659 225 mg	Immunogenicity Assessment of Anti-drug Antibodies (ADAs)	Day 1 (n =46, 52, 53)	1 events
PF-00547659 225 mg	Immunogenicity Assessment of Anti-drug Antibodies (ADAs)	Week 4 (n = 55, 52, 55)	2 events
PF-00547659 225 mg	Immunogenicity Assessment of Anti-drug Antibodies (ADAs)	Week 8 (n = 44, 47, 56)	1 events
PF-00547659 225 mg	Immunogenicity Assessment of Anti-drug Antibodies (ADAs)	Week 12 (n = 47, 51, 51)	1 events
PF-00547659 225 mg	Immunogenicity Assessment of Anti-drug Antibodies (ADAs)	Week 28 (n = 8, 1, 1)	0 events
PF-00547659 225 mg	Immunogenicity Assessment of Anti-drug Antibodies (ADAs)	Week 20 (n = 4, 3, 1)	0 events

Secondary

Number of Adverse Events (AEs) - PF-00547659 Dose Levels Versus Placebo

Number of adverse events (all causalities and treatment related) was reported between the investigational product groups and the placebo group.

Time frame: Week 0-12

Population: The safety analysis set included all participants who received at least 1 dose of study medication.

Arm	Measure	Group	Value (NUMBER)
PF-00547659 22.5 mg	Number of Adverse Events (AEs) - PF-00547659 Dose Levels Versus Placebo	Number of AEs (all causalities)	175 events
PF-00547659 22.5 mg	Number of Adverse Events (AEs) - PF-00547659 Dose Levels Versus Placebo	Number of AEs (treatment related)	40 events
PF-00547659 75 mg	Number of Adverse Events (AEs) - PF-00547659 Dose Levels Versus Placebo	Number of AEs (treatment related)	55 events
PF-00547659 75 mg	Number of Adverse Events (AEs) - PF-00547659 Dose Levels Versus Placebo	Number of AEs (all causalities)	192 events
PF-00547659 225 mg	Number of Adverse Events (AEs) - PF-00547659 Dose Levels Versus Placebo	Number of AEs (all causalities)	192 events
PF-00547659 225 mg	Number of Adverse Events (AEs) - PF-00547659 Dose Levels Versus Placebo	Number of AEs (treatment related)	64 events
Placebo	Number of Adverse Events (AEs) - PF-00547659 Dose Levels Versus Placebo	Number of AEs (all causalities)	141 events
Placebo	Number of Adverse Events (AEs) - PF-00547659 Dose Levels Versus Placebo	Number of AEs (treatment related)	40 events

Secondary

Percentage of Participants With a Crohn's Disease Activity Index (CDAI) Remission

Percentage of participants with a CDAI remission (defined as a CDAI reduction to \<150 points).

Time frame: Weeks 8 and week 12

Population: The full analysis set included all randomized participants who received at least one dose of study medication.

Arm	Measure	Group	Value (NUMBER)
PF-00547659 22.5 mg	Percentage of Participants With a Crohn's Disease Activity Index (CDAI) Remission	Week 8 (n = 50, 56, 62, 57)	29.1 Percentage of Participants
PF-00547659 22.5 mg	Percentage of Participants With a Crohn's Disease Activity Index (CDAI) Remission	Week 12 (n= 51, 49, 61, 55)	26.8 Percentage of Participants
PF-00547659 75 mg	Percentage of Participants With a Crohn's Disease Activity Index (CDAI) Remission	Week 12 (n= 51, 49, 61, 55)	28.5 Percentage of Participants
PF-00547659 75 mg	Percentage of Participants With a Crohn's Disease Activity Index (CDAI) Remission	Week 8 (n = 50, 56, 62, 57)	23.8 Percentage of Participants
PF-00547659 225 mg	Percentage of Participants With a Crohn's Disease Activity Index (CDAI) Remission	Week 8 (n = 50, 56, 62, 57)	26.9 Percentage of Participants
PF-00547659 225 mg	Percentage of Participants With a Crohn's Disease Activity Index (CDAI) Remission	Week 12 (n= 51, 49, 61, 55)	29.6 Percentage of Participants
Placebo	Percentage of Participants With a Crohn's Disease Activity Index (CDAI) Remission	Week 8 (n = 50, 56, 62, 57)	16.7 Percentage of Participants
Placebo	Percentage of Participants With a Crohn's Disease Activity Index (CDAI) Remission	Week 12 (n= 51, 49, 61, 55)	23.0 Percentage of Participants

Comparison: Difference from placebo at week 8p-value: 0.123490% CI: [-0.052, 0.299]Mixed Models Analysis

Comparison: Difference from placebo at week 8p-value: 0.237890% CI: [-0.092, 0.234]Mixed Models Analysis

Comparison: Difference from placebo at week 8p-value: 0.152990% CI: [-0.062, 0.266]Mixed Models Analysis

Comparison: Difference from placebo at week 12p-value: 0.366190% CI: [-0.146, 0.222]Mixed Models Analysis

Comparison: Difference from placebo at week 12p-value: 0.316990% CI: [-0.136, 0.246]Mixed Models Analysis

Comparison: Difference from placebo at week 12p-value: 0.275590% CI: [-0.116, 0.248]Mixed Models Analysis

Secondary

Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo

Number of participants with adverse events (AEs), withdrawals due to AEs and Serious AEs (SAEs) were reported.

Time frame: Week 0-12

Population: The safety analysis set included all participants who received at least 1 dose of study medication.

Arm	Measure	Group	Value (NUMBER)
PF-00547659 22.5 mg	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Participants with AEs (all causalities)	57 Number of participants
PF-00547659 22.5 mg	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Participants with AEs (treatment related)	20 Number of participants
PF-00547659 22.5 mg	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Withdrawal due to AEs (all causalities)	9 Number of participants
PF-00547659 22.5 mg	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Withdrawal due to AEs (treatment related)	5 Number of participants
PF-00547659 22.5 mg	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Participants with SAEs (all causalities)	11 Number of participants
PF-00547659 22.5 mg	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Participants with SAEs (treatment related)	4 Number of participants
PF-00547659 75 mg	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Participants with SAEs (treatment related)	4 Number of participants
PF-00547659 75 mg	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Withdrawal due to AEs (treatment related)	2 Number of participants
PF-00547659 75 mg	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Participants with AEs (all causalities)	51 Number of participants
PF-00547659 75 mg	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Withdrawal due to AEs (all causalities)	8 Number of participants
PF-00547659 75 mg	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Participants with AEs (treatment related)	24 Number of participants
PF-00547659 75 mg	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Participants with SAEs (all causalities)	9 Number of participants
PF-00547659 225 mg	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Participants with AEs (treatment related)	29 Number of participants
PF-00547659 225 mg	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Withdrawal due to AEs (all causalities)	4 Number of participants
PF-00547659 225 mg	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Withdrawal due to AEs (treatment related)	0 Number of participants
PF-00547659 225 mg	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Participants with SAEs (treatment related)	2 Number of participants
PF-00547659 225 mg	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Participants with SAEs (all causalities)	11 Number of participants
PF-00547659 225 mg	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Participants with AEs (all causalities)	54 Number of participants
Placebo	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Participants with SAEs (all causalities)	5 Number of participants
Placebo	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Participants with SAEs (treatment related)	2 Number of participants
Placebo	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Participants with AEs (treatment related)	22 Number of participants
Placebo	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Withdrawal due to AEs (treatment related)	1 Number of participants
Placebo	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Participants with AEs (all causalities)	54 Number of participants
Placebo	Safety and Tolerability of PF-00547659 Dose Levels Versus Placebo	Withdrawal due to AEs (all causalities)	3 Number of participants

Secondary

The Pharmacokinetics (PK) of Total PF-00547659 - Apparent Clearance (CL/F)

The Pharmacokinetics (PK) of total PF-00547659 was characterized using a population PK approach. PK parameters including but not limited to AUC, CL and half life were estimated using data pooled from both typical and additional PK groups. CL/F is apparent clearance.

Time frame: Day 1, 14, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224 and 252