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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01287897
• Collaborator: (none)
• Enrollment: 250
• Locations: 193
• Arms: 3
• Duration (Months): 48
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is a proof of concept study to determine the efficacy and safety of a monoclonal antibody with three doses versus placebo. Subjects will be randomized to a treatment and the dose will be delivered subcutaneously twice, 4 weeks apart. All subjects will have moderate to severe refractory Crohn's Disease.

Condition or Disease	Intervention/Treatment	Phase
Crohn's Disease	Drug: PF-04236921 SC injection; Drug: PF-04236921 SC injection; Drug: PF-04236921 SC injection	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 250 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Randomized, Placebo-controlled, Dose-ranging Study To Evaluate The Efficacy And Safety Of Pf-04236921 In Subjects With Crohn's Disease Who Are Anti-tnf Inadequate Responders (Andante)
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Sep 1, 2014
• Actual Study Completion Date: Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo- SC injection	Drug: PF-04236921 SC injection; Placebo delivered SC, 2 doses separated by 4 weeks
Experimental: Drug Dose level 1 - SC injection	Drug: PF-04236921 SC injection; Drug dose level 1 delivered SC, 2 doses separated by 4 weeks
Experimental: Drug Dose level 2 - SC injection	Drug: PF-04236921 SC injection; Drug dose level 2 delivered SC, 2 doses separated by 4 weeks

Outcome Measures

Primary Outcome Measures

1. The Crohn's Disease Activity Index (CDAI)-70 Response Rate at Week 8 in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg [Baseline and Week 8]

   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).

2. The CDAI-70 Response Rate at Week 8 in Participants Who Received Placebo and PF-04236921 200 mg [Baseline and Week 8]

   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.

3. The CDAI-70 Response Rate at Week 12 in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg [Baseline and Week 12]

   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).

4. The CDAI-70 Response Rate at Week 12 in Participants Who Received Placebo and PF-04236921 200 mg [Baseline and Week 12]

   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.

Secondary Outcome Measures

1. The CDAI-70 Response Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg [Baseline and Weeks 2, 4, 6, and 10]

   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).

2. The CDAI-70 Response Rate Over Time in Participants Who Received Placebo and PF-04236921 200 mg [Baseline and Weeks 2, 4, 6, and 10]

   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.

3. The CDAI Remission Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg [Baseline and Weeks 2, 4, 6, 8, 10, and 12]

   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).

4. The CDAI Remission Rate Over Time in Participants Who Received Placebo and PF-04236921 200 mg [Baseline and Weeks 2, 4, 6, 8, 10, and 12]

   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.

5. The CDAI-100 Response Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg [Baseline and Weeks 2, 4, 6, 8, 10, and 12]

   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).

6. The CDAI-100 Response Rate Over Time in Participants Who Received Placebo and PF-04236921 200 mg [Baseline and Weeks 2, 4, 6, 8, 10, and 12]

   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.

7. Change From Baseline in CDAI Score Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg [Baseline and Weeks 2, 4, 6, 8, 10, and 12]

   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).

8. Change From Baseline in CDAI Score Over Time in Participants Who Received Placebo and PF-04236921 200 mg [Baseline and Weeks 2, 4, 6, 8, 10, and 12]

   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.

9. Percentages of Participants With Confirmed Positive Anti-drug Antibodies (ADAs) [At baseline (Day 1) and at Weeks 4, 8, 12, 16, 24, 32 and 40]

   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.

10. Percentages of Participants With Confirmed Positive Neutralizing Antibodies (NAbs) [At baseline (Day 1) and at Weeks 4, 8, 12, 16, 24, 32 and 40]

    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.

11. Serum PF-04236921 Concentration Over Time [Day 1 (predose), and at Weeks 2, 4 (Day 28, predose), 8, 10, 12, 16, 20, 24, 28, 32, 36, and 40]

12. Number of Participants Who Withdrew From the Study Due to Treatment-emergent Adverse Events (AEs) [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)]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects must have failed or are intolerant to anti TNFs

• hsCRP greater or equal to 5.0 mg/L

• Ulcerations demonstrated by colonoscopy as defined by SES CD assessment performed within 8 weeks of study entry (screening) and able to retrospectively complete the SES-CD or colonoscopy performed during screening

Exclusion Criteria:

• Pregnant or breastfeeding women

• Crohn's Disease with active fistulae or abscess

• History of diverticulitis or symptomatic diverticulosis

• Abnormality in hematology or chemistry profiles at screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UAB Hospital	Birmingham	Alabama	United States	35249
2	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
3	Simon Medical Imaging	Scottsdale	Arizona	United States	85258
4	Digestive Health Research Unit	Scottsdale	Arizona	United States	85260
5	Adobe Clinical Research, Llc	Tucson	Arizona	United States	85712
6	Radiology Ltd	Tucson	Arizona	United States	85712
7	UCSF Endoscopy Unit at Mount Zion	San Francisco	California	United States	94115
8	University of California - San Francisco	San Francisco	California	United States	94115
9	University of California San Francisco at Mount Zion	San Francisco	California	United States	94115
10	Rocky Mountain Clinical Research, LLC	Denver	Colorado	United States	80222
11	Rocky Mountain Gastroenterology Associates	Lakewood	Colorado	United States	80215
12	Rocky Mountain Gastroenterology	Lakewood	Colorado	United States	80215
13	Arapahoe Gastroenterology, PC	Littleton	Colorado	United States	80120
14	Endoscopy Center of Connecticut, LLC	Guilford	Connecticut	United States	06437
15	Endoscopy Center of Connecticut, LLC	Hamden	Connecticut	United States	06518
16	Gastroenterology Center of Connecticut, PC	Hamden	Connecticut	United States	06518
17	Medical Research Center of Connecticut, LLC	Hamden	Connecticut	United States	06518
18	Clinical Research of West Florida, Inc.	Clearwater	Florida	United States	33765
19	Gastroenterology Associates	Crystal River	Florida	United States	34429
20	Nature Coast Clinical Research	Inverness	Florida	United States	34452
21	Suncoast Endoscopy Center	Inverness	Florida	United States	34453
22	Advanced Research Institute, Inc.	New Port Richey	Florida	United States	34653
23	International Clinical Research - US, LLC	Sanford	Florida	United States	32771
24	Atlanta Center for Gastroenterology, P.C.	Decatur	Georgia	United States	30033
25	Atlanta Endoscopy Center	Decatur	Georgia	United States	30033
26	Decatur Health Imaging	Decatur	Georgia	United States	30033
27	Gastrointestinal Specialists of Georgia, PC	Marietta	Georgia	United States	30060
28	GI Diagnostics	Marietta	Georgia	United States	30067
29	Illinois Gastroenterology Group, LLC	Arlington Heights	Illinois	United States	60005
30	The University of Chicago Medical Center (Ucmc)	Chicago	Illinois	United States	60637
31	The University of Chicago Medical Center	Chicago	Illinois	United States	60637
32	The University of Chicago Medical	Chicago	Illinois	United States	60637
33	The University Of Chicago	Chicago	Illinois	United States	60637
34	NorthShore University Health System	Evanston	Illinois	United States	60201
35	Glenbrook Hospital Outpatient Pharmacy	Glenview	Illinois	United States	60025
36	Glenbrook Hospital	Glenview	Illinois	United States	60026
37	Central Indiana Gastroenterology Group	Anderson	Indiana	United States	46016
38	Saint John's Research Institute	Anderson	Indiana	United States	46016
39	University of Kentucky	Lexington	Kentucky	United States	40536
40	University Of Louisville Healthcare Outpatient Center	Louisville	Kentucky	United States	40202
41	University of Louisville Research Foundation	Louisville	Kentucky	United States	40202
42	University Of Louisville	Louisville	Kentucky	United States	40202
43	Digestive Disorders Associates	Annapolis	Maryland	United States	21401
44	Disgestive Disorders Associates	Annapolis	Maryland	United States	21401
45	Investigative Clinical Research	Annapolis	Maryland	United States	21401
46	Maryland Diagnostics & Therapeutic Endo Center	Annapolis	Maryland	United States	21401
47	Commonwealth Clinical Studies	Brockton	Massachusetts	United States	02302
48	Prima CARE, PC	Fall River	Massachusetts	United States	02721
49	St. Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
50	East Valley Endoscopy	Grand Rapids	Michigan	United States	49546
51	Gastroenterology Associates of Western Michigan	Wyoming	Michigan	United States	49519
52	Metro Health Hospital Endoscopy Unit	Wyoming	Michigan	United States	49519
53	Metro Health Hospital	Wyoming	Michigan	United States	49519
54	Huron Gastroenterology Associates	Ypsilanti	Michigan	United States	48197
55	St. Joseph Mercy Hospital	Ypsilanti	Michigan	United States	48197
56	Minnesota Gastroenterology, PA	Plymouth	Minnesota	United States	55446
57	Weill Cornell Medical College of Cornell University-Greenberg	New York	New York	United States	10021
58	Weill Cornell Medical College of Cornell University	New York	New York	United States	10021
59	Present Chapman, Steinlauf and Marion	New York	New York	United States	10028
60	Mount Sinai School of Medicine	New York	New York	United States	10029
61	New York Presbyterian Hospital - Weill Cornell Medical College Investigational Pharmacy	New York	New York	United States	10065
62	New York Presbyterian Hospital	New York	New York	United States	10065
63	Weill Cornell Imaging at New York Presbyterian Hospital	New York	New York	United States	10065
64	Arthur asher Kornbluth, MD PC	New York	New York	United States	10128
65	PMG Research of Winston-Salem	Winston-Salem	North Carolina	United States	27103
66	Oklahoma Foundation for Digestive Research	Oklahoma City	Oklahoma	United States	73102
67	Pharmacy: Wheeler and Stuckey, Inc.	Oklahoma City	Oklahoma	United States	73103
68	Colonoscopy and X-rays: OU Physicians Building	Oklahoma City	Oklahoma	United States	73104
69	Hillcrest Medical Center Endoscopy	Tulsa	Oklahoma	United States	74104
70	Hillcrest Medical Center	Tulsa	Oklahoma	United States	74104
71	Options Health Research, LLC	Tulsa	Oklahoma	United States	74104
72	Utica Park Clinic X-Ray	Tulsa	Oklahoma	United States	74104
73	Advanced Imaging	Tulsa	Oklahoma	United States	74137-4200
74	Pittsburgh Gastroenterology Associates	Pittsburgh	Pennsylvania	United States	15243
75	Research Protocol Management Specialists	Pittsburgh	Pennsylvania	United States	15243
76	Pharma Resource	East Providence	Rhode Island	United States	02915
77	Omega Medical Research	Warwick	Rhode Island	United States	02886
78	Gastro One	Germantown	Tennessee	United States	38138
79	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37212
80	Professional Quality Research, Inc.	Austin	Texas	United States	78705
81	Diagnostic Clinic of Houston, PA	Houston	Texas	United States	77004
82	Houston Hospital for Specialized Surgery (Endoscopy Only)	Houston	Texas	United States	77004
83	Baylor Clinic (Drug Storage)	Houston	Texas	United States	77030
84	Baylor College of Medicine - Baylor Medical Center	Houston	Texas	United States	77030
85	Ertan Digestive Disease Center	Houston	Texas	United States	77030
86	Memorial Hermann Hospital	Houston	Texas	United States	77030
87	The University of Texas Health Science Center at Houston	Houston	Texas	United States	77030
88	The University of Texas Medical School at Houston	Houston	Texas	United States	77030
89	Physicians Endoscopy Center (Colonoscopy)	Houston	Texas	United States	77036
90	Texas Digestive Disease Consultants	Southlake	Texas	United States	76092
91	One Step Diagnostic (X-Ray)	Sugar Land	Texas	United States	77478
92	Pioneer Research Solutions, Inc. (Admin. Office)	Sugar Land	Texas	United States	77479
93	Pioneer Research Solutions, Inc.	SugarLand	Texas	United States	77479
94	Digestive Health Specialists of Tyler	Tyler	Texas	United States	75701
95	University Of Utah HSC	Salt Lake City	Utah	United States	84132
96	Virginia Commonwealth University	Richmond	Virginia	United States	23298-0341
97	Virginia Commonwealth University	Richmond	Virginia	United States	23298
98	VCU Medical Investigational Drug Service (IDS)	Richmond	Virginia	United States	93298-5028
99	Concord Repatriation General Hospital	Concord	New South Wales	Australia	2139
100	Nepean Public Hospital	Kingswood	New South Wales	Australia	2747
101	Royal Brisbane and Women's Hospital	Herston, Brisbane	Queensland	Australia	4029
102	Mater Health Services	South Brisbane	Queensland	Australia	4101
103	Eastern Health, Box Hill Hospital	Box Hill	Victoria	Australia	3128
104	Monash Medical Centre	Clayton	Victoria	Australia	3168
105	The Royal Melbourne Hospital	Parkville	Victoria	Australia	3050
106	St. Vincent's Hospital Melbourne	Fitzroy		Australia	VIC 3065
107	University Hospital Leuven	Leuven	Vlaams Brabant	Belgium	3000
108	CHU Saint-Pierre	Bruxelles		Belgium	1000
109	UZ Leuven Pharmacy	Leuven		Belgium	3000
110	An Spiessens H.-Hartziekenhuis Roeselare-Menen vzw	Roeselare		Belgium	B-8800
111	Clinica do Coracao Samaritano	Goiania	GO	Brazil	74535-170
112	Instituto Goiano de Gastroenterologia e Endoscopia Digestiva Ltda.	Goiania	GO	Brazil	74535-170
113	Center X Diagnosticos	Goiania	GO	Brazil	74535-900
114	Hospital Universitário Fraga Filho da UFRJ	Rio de Janeiro	RJ	Brazil	21941-913
115	Hospital Sao Lucas da PUCRS	Porto Alegre	RS	Brazil	90610-000
116	Faculdade de Medicina do ABC	Santo Andre	SP	Brazil	09060-650
117	Hospital Israelita Albert Einstein	São Paulo	SP	Brazil	05651-901
118	Hospital Nossa Senhora das Gracas	Curitiba		Brazil	80810-040
119	Heritage Medical Research Clinic - University of Calgary	Calgary	Alberta	Canada	T2N 4Z6
120	London Health Science Centre - University Hospital	London	Ontario	Canada	N6A 5A5
121	Mount Sinai Hospital	Toronto	Ontario	Canada	M5G 1X5
122	McGill University Health Centre - Royal Victoria Hospital	Montreal	Quebec	Canada	H3A 1A1
123	Hepato-Gastroenterologie HK, s.r.o.	Hradec Kralove		Czech Republic	500 12
124	Medial Pharma s.r.o.,	Hradec Kralove		Czech Republic	500 12
125	Fakultni nemocnice Olomouc	Olomouc		Czech Republic	775 20
126	Klinicke centrum ISCARE I.V.F. - gastroenterologie	Prague		Czech Republic	170 04
127	Fakultni nemocnice Kralovske Vinohrady	Praha 10		Czech Republic	100 34
128	Institut klinicke a experimentalni mediciny	Praha 4		Czech Republic	14021
129	IBD Clinical and Research centre	Praha 7		Czech Republic
130	Krajska zdravotni, a.s.	Usti nad Labem		Czech Republic	40113
131	Aalborg Sygehus	Aalborg		Denmark	9100
132	Aarhus Universitetshospital, Aarhus Sygehus Aarhus University Hospital	Aarhus C		Denmark	8000
133	Gastroenheden	Herlev		Denmark	2730
134	Kirurgisk Afdeling 0143	Hilleroed		Denmark	3400
135	Hvidovre Hospital	Hvidovre		Denmark	2650
136	Afdeling I, Gastroenterologisk Sektion	Koebenhavn NV		Denmark	2400
137	Rigshospitalet	Koebenhavn		Denmark	2100
138	Medicinsk Afdeling, Gastroenterologisk Sektion	Koege		Denmark	4600
139	Hopital Huriez, CHRU de Lille	Lille Cedex		France	59037
140	Hopital Saint-Antoine - Service De Gastroenterologie	Paris Cedex 12		France	75571
141	Hopital de Brabois	Vandoeuvre Les Nancy		France	54500
142	Medizinische Hochschule Hannover	Hannover	Niedersachsen	Germany	30625
143	"Charite - Campus Benjamin Franklin	Berlin		Germany	12200
144	Praxis Dr. Howaldt	Hamburg		Germany	20148
145	Universitaetsklinikum Schleswig-Holstein	Kiel		Germany	24105
146	Gastroenterologische Gemeinschaftspraxis Minden	Minden		Germany	32423
147	Universitaetsklinik Regensburg	Regensburg		Germany	93053
148	University General Hospital "Attikon"	Athens		Greece	12462
149	General Hospital of Athens "Evangelismos",1st Gastroenterology Department	Kolonaki Athens		Greece	106 76
150	Semmelweis Egyetem II. Sz. Belgyogyaszati Klinika	Budapest		Hungary	1088
151	Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak./I. Belgyogyaszati-Gasztroenterologiai	Budapest		Hungary	1125
152	Pannonia Maganorvosi Centrum Kft.	Budapest		Hungary	1136
153	Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum	Debrecen		Hungary	4032
154	Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar / I. sz. Belgyogyaszati Klinika	Szeged		Hungary	6720
155	Clinfan Kft.	Szekszard		Hungary	7100
156	St. Vincents University Hospital	Dublin 4		Ireland
157	Beaumont Hospital	Dublin		Ireland	9
158	National Virus Reference Laboratory	Dublin		Ireland	Dublin 4
159	Pathology, Haematology and Biochemistry Laboratories, St Vincent's Healthcare Group	Dublin		Ireland	Dublin 4
160	Mater Misericordiae Hospital, Department of Clinical Chemistry and Clinical Haematology	Dublin		Ireland	Dublin 7
161	University Hospital Galway	Galway		Ireland
162	The Institute Of Gastroenterology & Liver Diseases	Tel Hashomer	Ramat Gan	Israel	52621
163	Institute of Gastroenterology	Haifa		Israel	3339419
164	The E. Wolfson Medical Center	Holon		Israel	58100
165	Shaare Zedek Medical Center	Jerusalem		Israel	91031
166	Hadassah Medical Center	Jerusalem		Israel	91120
167	Dept of Gastroenterology & Hepatology	Kfar Saba		Israel	44281
168	Rabin Medical Center, Beilinson Hospital	Petach Tikva		Israel	49100
169	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	64239
170	Assaf Harofeh Medical Center	Zerifin		Israel	70300
171	Casa Sollievo della Sofferenza/Div.Gastroenterologia Endoscopia Digestiva	San Giovanni Rotondo Fg	Foggia	Italy	71013
172	Istituto Clinico Humanitas IRCCS	Rozzano	Milano	Italy	20089
173	A. Gemelli University Hospital-Department of Medical Sciences - Division of Internal Medicine and	Rome	Province of Rome	Italy	00168
174	Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola Malpighi	Bologna		Italy	40138
175	Azienda Ospedaliera - Universita di Padova	Padova		Italy	35128
176	Università Campus Biomedico	Roma		Italy	00128
177	Policlinico Tor Vergata	Roma		Italy	00133
178	Azienda Ospedaliera San Camillo Forlanini	Roma		Italy	00151
179	Shakespeare Specialist Group	Milford	Auckland	New Zealand	0620
180	Christchurch Hospital	Christchurch	Canterbury	New Zealand	8011
181	Department of Gastroenterology Research	Hamilton	Waikato	New Zealand	3204
182	P3 Research Limited	Wellington		New Zealand	6021
183	Spitalul Clinic Colentina	Bucuresti	Sector 2	Romania	020125
184	Universitaetsspital Zuerich	Zuerich		Switzerland	8091
185	Hull and East Yorkshire Hospitals NHS Trust	Hull	East Yorkshire	United Kingdom	HU3 2JZ
186	Addenbrooke's Hospital, Department of Gastroenterology	Cambridge		United Kingdom	CB2 0QQ
187	Glasgow Royal Infirmary	Glasgow		United Kingdom	G40SS
188	Pharmacy Department	Hull		United Kingdom	HU3 2JZ
189	Barts and The London NHS Trust	London		United Kingdom	E1 1BB
190	Royal Free Hospital (Royal Free London NHS Foundation Trust)	London		United Kingdom	NW3 2QG
191	Royal Victoria Hospital	Newcastle-upon-Tyne		United Kingdom	NE1 4LP
192	New Cross Hospital	Wolverhampton		United Kingdom	WV10 0QP
193	Newcross Hospital-The Royal Wolverhampton Hospitals NHS Trust	Wolverhampton		United Kingdom	WV69AT

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01287897
• Other Study ID Numbers: B0151003; 2010-023034-23; ANDANTE
• First Posted: Feb 2, 2011
• Last Update Posted: Jan 21, 2016
• Last Verified: Dec 1, 2015

• Keywords provided by Pfizer: Crohn's Disease; safety; efficacy; pharmacokinetics; pharmacodynamics; Crohn's Disease Activity Index (CDAI)
• Additional relevant MeSH terms: Crohn Disease

Study Results

Participant Flow

Recruitment Details	This study included a 28-day screening period, an induction period (Week 0-12) and a 28-week follow-up period. Participants who completed the induction treatment period could enter the follow-up period or an open-label extension study, NCT01345318. Participants who discontinued treatment during the induction period could enter the follow-up period.
Pre-assignment Detail	A total of 250 participants were randomized via Interactive Voice Response System (IVRS); of which, 247 received investigational product and 3 were randomized inadvertently and not dosed (2 did not meet entrance criteria and 1 did not consent properly and was not included in clinical database because the randomization page was not completed).

Arm/Group Title	Placebo	PF-04236921 10 Milligram (mg)	PF-04236921 50 mg	PF-04236921 200 mg
Arm/Group Description	Placebo administered subcutaneously (SC) in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 10 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 50 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 200 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.
Period Title: Overall Study
STARTED	70	69	71	40
Treated	69	67	71	40
Completed Treatment Period	58	52	58	29
Completed Follow-up Period	3	8	3	4
Enrolled in NCT01345318	56	50	56	29
COMPLETED	59	58	59	33
NOT COMPLETED	11	11	12	7

Baseline Characteristics

Arm/Group Title	Placebo	PF-04236921 10 mg	PF-04236921 50 mg	PF-04236921 200 mg	Total
Arm/Group Description	Placebo administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 10 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 50 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 200 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	Total of all reporting groups
Overall Participants	69	67	71	40	247
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	38.4 (13.6)	38.9 (12.9)	38.9 (13.1)	42.2 (13.2)	39.3 (13.2)
Sex: Female, Male (Count of Participants)
Female	38 55.1%	34 50.7%	44 62%	25 62.5%	141 57.1%
Male	31 44.9%	33 49.3%	27 38%	15 37.5%	106 42.9%

Outcome Measures

1. Primary Outcome

Title	The Crohn's Disease Activity Index (CDAI)-70 Response Rate at Week 8 in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg
Description	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Placebo	PF-04236921 10 mg	PF-04236921 50 mg
Arm/Group Description	Placebo administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 10 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 50 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.
Measure Participants	69	65	71
Least Squares Mean (90% Confidence Interval) [Percentage of participants]	30.6 44.3%	35.0 52.2%	49.3 69.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3406
	Comments	Type I rate was controlled for the 2 time points (Week 8 and Week 12) at 0.05 (one sided).
	Method	Generalized linear mixed model (GLMM)
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.3
	Confidence Interval	(2-Sided) 90%; -13.0 to 21.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 10.5
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0438
	Comments	Type I rate was controlled for the 2 time points (Week 8 and Week 12) at 0.05 (one sided).
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	18.7
	Confidence Interval	(2-Sided) 90%; 0.7 to 36.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 11.0
	Estimation Comments

2. Primary Outcome

Title	The CDAI-70 Response Rate at Week 8 in Participants Who Received Placebo and PF-04236921 200 mg
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	PF-04236921 200 mg
Arm/Group Description	Placebo administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 200 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.
Measure Participants	69	40
Least Squares Mean (90% Confidence Interval) [Percentage of participants]	28.8 41.7%	39.0 58.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2258
	Comments	Type I rate was controlled for the 2 time points (Week 8 and Week 12) at 0.05 (one sided).
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	10.2
	Confidence Interval	(2-Sided) 90%; -12.1 to 32.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 13.6
	Estimation Comments

3. Primary Outcome

Title	The CDAI-70 Response Rate at Week 12 in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg
Description	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Placebo	PF-04236921 10 mg	PF-04236921 50 mg
Arm/Group Description	Placebo administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 10 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 50 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.
Measure Participants	69	65	71
Least Squares Mean (90% Confidence Interval) [Percentage of participants]	28.6 41.4%	35.2 52.5%	47.4 66.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2627
	Comments	Type I rate was controlled for the 2 time points (Week 8 and Week 12) at 0.05 (one sided).
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	6.7
	Confidence Interval	(2-Sided) 90%; -10.6 to 23.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 10.5
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0425
	Comments	Type I rate was controlled for the 2 time points (Week 8 and Week 12) at 0.05 (one sided).
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	18.8
	Confidence Interval	(2-Sided) 90%; 0.8 to 36.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 10.9
	Estimation Comments

4. Primary Outcome

Title	The CDAI-70 Response Rate at Week 12 in Participants Who Received Placebo and PF-04236921 200 mg
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	PF-04236921 200 mg
Arm/Group Description	Placebo administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 200 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.
Measure Participants	69	40
Least Squares Mean (90% Confidence Interval) [Percentage of participants]	26.7 38.7%	41.7 62.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1362
	Comments	Type I rate was controlled for the 2 time points (Week 8 and Week 12) at 0.05 (one sided).
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	15.1
	Confidence Interval	(2-Sided) 90%; -7.5 to 37.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 13.7
	Estimation Comments

5. Secondary Outcome

Title	The CDAI-70 Response Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	PF-04236921 10 mg	PF-04236921 50 mg
Arm/Group Description	Placebo administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 10 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 50 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.
Measure Participants	69	65	71
Week 2 (n=64, 63, 65)	12.3 17.8%	19.4 29%	18.1 25.5%
Week 4 (n=66, 58, 59)	16.5 23.9%	34.6 51.6%	37.0 52.1%
Week 6 (n=58, 53, 60)	21.1 30.6%	35.0 52.2%	46.2 65.1%
Week 10 (n=54, 50, 51)	29.3 42.5%	38.9 58.1%	54.0 76.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI-70 response rate for the 10-mg arm at Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1527
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	7.1
	Confidence Interval	(2-Sided) 90%; -4.3 to 18.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.0
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI-70 response rate for the 10-mg arm at Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0235
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	18.1
	Confidence Interval	(2-Sided) 90%; 3.1 to 33.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.1
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI-70 response rate for the 10-mg arm at Week 6.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0792
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	13.9
	Confidence Interval	(2-Sided) 90%; -2.3 to 30.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.9
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI-70 response rate for the 10-mg arm at Week 10.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1909
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	9.6
	Confidence Interval	() 90%; -8.4 to 27.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 11.0
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments	LSM difference from placebo in CDAI-70 response rate for the 50-mg arm at Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1981
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.8
	Confidence Interval	(2-Sided) 90%; -5.4 to 17.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.8
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments	LSM difference from placebo in CDAI-70 response rate for the 50-mg arm at Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0132
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	20.6
	Confidence Interval	(2-Sided) 90%; 5.3 to 35.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.3
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments	LSM difference from placebo in CDAI-70 response rate for the 50-mg arm at Week 6.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0063
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	25.1
	Confidence Interval	(2-Sided) 90%; 8.6 to 41.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 10.1
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments	LSM difference from placebo in CDAI-70 response rate for the 50-mg arm at Week 10.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0138
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	24.7
	Confidence Interval	(2-Sided) 90%; 6.2 to 43.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 11.2
	Estimation Comments

6. Secondary Outcome

Title	The CDAI-70 Response Rate Over Time in Participants Who Received Placebo and PF-04236921 200 mg
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	PF-04236921 200 mg
Arm/Group Description	Placebo administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 200 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.
Measure Participants	69	40
Week 2 (n=64, 36)	11.2 16.2%	26.5 39.6%
Week 4 (n=66, 35)	15.2 22%	24.6 36.7%
Week 6 (n=58, 32)	19.5 28.3%	27.2 40.6%
Week 10 (n=54, 29)	27.2 39.4%	46.3 69.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI-70 response rate for the 200-mg arm at Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0662
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	15.4
	Confidence Interval	(2-Sided) 90%; -1.4 to 32.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 10.2
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI-70 response rate for the 200-mg arm at Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1708
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	9.5
	Confidence Interval	(2-Sided) 90%; -6.9 to 25.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 10.0
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI-70 response rate for the 200-mg arm at Week 6.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2416
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	7.8
	Confidence Interval	(2-Sided) 90%; -10.5 to 26.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 11.1
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI-70 response rate for the 200-mg arm at Week 10.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0880
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	19.1
	Confidence Interval	(2-Sided) 90%; -4.1 to 42.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 14.1
	Estimation Comments

7. Secondary Outcome

Title	The CDAI Remission Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	PF-04236921 10 mg	PF-04236921 50 mg
Arm/Group Description	Placebo administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 10 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 50 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.
Measure Participants	69	65	71
Week 2 (n=64, 63, 68)	1.6 2.3%	3.6 5.4%	9.6 13.5%
Week 4 (n=66, 58, 62)	3.4 4.9%	4.1 6.1%	19.7 27.7%
Week 6 (n=58, 53, 63)	8.5 12.3%	7.3 10.9%	23.4 33%
Week 8 (n=58, 53, 58)	16.3 23.6%	10.8 16.1%	24.9 35.1%
Week 10 (n=54, 50, 54)	13.1 19%	19.9 29.7%	30.9 43.5%
Week 12 (n=57, 52, 57)	10.9 15.8%	10.8 16.1%	27.4 38.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI remission rate for the 10-mg arm at Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2610
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience and concomitant immunosuppressant therapy were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 90%; -3.2 to 7.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.2
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI remission rate for the 10-mg arm at Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4291
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience and concomitant immunosuppressant therapy were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 90%; -5.6 to 7.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.8
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI remission rate for the 10-mg arm at Week 6.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5791
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience and concomitant immunosuppressant therapy were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 90%; -11.0 to 8.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.0
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI remission rate for the 10-mg arm at Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7544
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience and concomitant immunosuppressant therapy were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.5
	Confidence Interval	(2-Sided) 90%; -18.8 to 7.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.0
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI remission rate for the 10-mg arm at Week 10.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2308
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience and concomitant immunosuppressant therapy were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	6.8
	Confidence Interval	() 90%; -8.3 to 21.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.2
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI remission rate for the 10-mg arm at Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5038
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience and concomitant immunosuppressant therapy were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 90%; -11.8 to 11.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.1
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments	LSM difference from placebo in CDAI remission rate for the 50-mg arm at Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0498
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience and concomitant immunosuppressant therapy were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	8.0
	Confidence Interval	(2-Sided) 90%; 0.0 to 16.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.9
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments	LSM difference from placebo in CDAI remission rate for the 50-mg arm at Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0155
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience and concomitant immunosuppressant therapy were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	16.3
	Confidence Interval	(2-Sided) 90%; 3.9 to 28.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.6
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments	LSM difference from placebo in CDAI remission rate for the 50-mg arm at Week 6.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0399
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience and concomitant immunosuppressant therapy were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	14.9
	Confidence Interval	(2-Sided) 90%; 0.9 to 28.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.5
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments	LSM difference from placebo in CDAI remission rate for the 50-mg arm at Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1866
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience and concomitant immunosuppressant therapy were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	8.5
	Confidence Interval	(2-Sided) 90%; -7.2 to 24.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.6
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments	LSM difference from placebo in CDAI remission rate for the 50-mg arm at Week 10.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0415
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience and concomitant immunosuppressant therapy were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	17.8
	Confidence Interval	(2-Sided) 90%; 0.9 to 34.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 10.3
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments	LSM difference from placebo in CDAI remission rate for the 50-mg arm at Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0408
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience and concomitant immunosuppressant therapy were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	16.5
	Confidence Interval	(2-Sided) 90%; 0.9 to 32.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.5
	Estimation Comments

8. Secondary Outcome

Title	The CDAI Remission Rate Over Time in Participants Who Received Placebo and PF-04236921 200 mg
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	PF-04236921 200 mg
Arm/Group Description	Placebo administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 200 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.
Measure Participants	69	40
Week 2 (n=64, 36)	1.1 1.6%	6.9 10.3%
Week 4 (n=66, 35)	2.4 3.5%	5.1 7.6%
Week 6 (n=58, 32)	6.1 8.8%	8.8 13.1%
Week 8 (n=58, 29)	11.9 17.2%	8.8 13.1%
Week 10 (n=54, 29)	9.4 13.6%	14.8 22.1%
Week 12 (n=57, 29)	7.8 11.3%	11.8 17.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI remission rate for the 200-mg arm at Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1342
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience and concomitant immunosuppressant therapy were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.8
	Confidence Interval	(2-Sided) 90%; -2.8 to 14.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.3
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI remission rate for the 200-mg arm at Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2623
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience and concomitant immunosuppressant therapy were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.7
	Confidence Interval	(2-Sided) 90%; -4.3 to 9.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.3
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI remission rate for the 200-mg arm at Week 6.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3324
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience and concomitant immunosuppressant therapy were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.7
	Confidence Interval	(2-Sided) 90%; -7.7 to 13.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.3
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI remission rate for the 200-mg arm at Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6637
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience and concomitant immunosuppressant therapy were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.2
	Confidence Interval	(2-Sided) 90%; -15.5 to 9.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.5
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI remission rate for the 200-mg arm at Week 10.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2721
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience and concomitant immunosuppressant therapy were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.4
	Confidence Interval	() 90%; -9.3 to 20.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.0
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI remission rate for the 200-mg arm at Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3022
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience and concomitant immunosuppressant therapy were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.0
	Confidence Interval	(2-Sided) 90%; -8.8 to 16.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.8
	Estimation Comments

9. Secondary Outcome

Title	The CDAI-100 Response Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	PF-04236921 10 mg	PF-04236921 50 mg
Arm/Group Description	Placebo administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 10 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 50 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.
Measure Participants	69	65	71
Week 2 (n=64, 63, 65)	12.4 18%	16.7 24.9%	12.6 17.7%
Week 4 (n=66, 58, 59)	13.0 18.8%	18.1 27%	26.3 37%
Week 6 (n=58, 53, 60)	14.5 21%	28.7 42.8%	32.2 45.4%
Week 8 (n=58, 53, 56)	24.1 34.9%	26.5 39.6%	37.9 53.4%
Week 10 (n=54, 50, 51)	21.0 30.4%	29.8 44.5%	38.2 53.8%
Week 12 (n=57, 52, 54)	22.2 32.2%	32.7 48.8%	36.2 51%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI-100 response rate for the 10-mg arm at Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2687
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.3
	Confidence Interval	(2-Sided) 90%; -7.2 to 15.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.0
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI-100 response rate for the 10-mg arm at Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2460
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.1
	Confidence Interval	(2-Sided) 90%; -7.1 to 17.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.4
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI-100 response rate for the 10-mg arm at Week 6.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0633
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	14.2
	Confidence Interval	(2-Sided) 90%; -1.1 to 29.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.3
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI-100 response rate for the 10-mg arm at Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4036
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.4
	Confidence Interval	(2-Sided) 90%; -13.8 to 18.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.9
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI-100 response rate for the 10-mg arm at Week 10.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1921
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	8.9
	Confidence Interval	() 90%; -7.9 to 25.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 10.2
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI-100 response rate for the 10-mg arm at Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1541
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	10.5
	Confidence Interval	(2-Sided) 90%; -6.5 to 27.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 10.3
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments	LSM difference from placebo in CDAI-100 response rate for the 50-mg arm at Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4893
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 90%; -10.5 to 10.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.5
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments	LSM difference from placebo in CDAI-100 response rate for the 50-mg arm at Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0619
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	13.2
	Confidence Interval	(2-Sided) 90%; -0.9 to 27.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.6
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments	LSM difference from placebo in CDAI-100 response rate for the 50-mg arm at Week 6.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0290
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	17.7
	Confidence Interval	(2-Sided) 90%; 2.3 to 33.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.3
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments	LSM difference from placebo in CDAI-100 response rate for the 50-mg arm at Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0988
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	13.8
	Confidence Interval	(2-Sided) 90%; -3.8 to 31.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 10.7
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments	LSM difference from placebo in CDAI-100 response rate for the 50-mg arm at Week 10.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0549
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	17.2
	Confidence Interval	(2-Sided) 90%; -0.5 to 35.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 10.8
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments	LSM difference from placebo in CDAI-100 response rate for the 50-mg arm at Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0920
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	14.0
	Confidence Interval	(2-Sided) 90%; -3.3 to 31.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 10.5
	Estimation Comments

10. Secondary Outcome

Title	The CDAI-100 Response Rate Over Time in Participants Who Received Placebo and PF-04236921 200 mg
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	PF-04236921 200 mg
Arm/Group Description	Placebo administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 200 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.
Measure Participants	69	40
Week 2 (n=64, 36)	10.3 14.9%	12.0 17.9%
Week 4 (n=66, 35)	11.0 15.9%	22.1 33%
Week 6 (n=58, 32)	12.2 17.7%	22.2 33.1%
Week 8 (n=58, 29)	21.3 30.9%	18.7 27.9%
Week 10 (n=54, 29)	18.2 26.4%	30.4 45.4%
Week 12 (n=57, 29)	19.4 28.1%	26.9 40.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI-100 response rate for the 200-mg arm at Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4031
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.7
	Confidence Interval	(2-Sided) 90%; -9.5 to 12.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.8
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI-100 response rate for the 200-mg arm at Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1219
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	11.1
	Confidence Interval	(2-Sided) 90%; -4.6 to 26.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.6
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI-100 response rate for the 200-mg arm at Week 6.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1600
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	9.9
	Confidence Interval	(2-Sided) 90%; -6.5 to 26.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 10.0
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI-100 response rate for the 200-mg arm at Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6019
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.7
	Confidence Interval	(2-Sided) 90%; -19.5 to 14.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 10.3
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI-100 response rate for the 200-mg arm at Week 10.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1601
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	12.3
	Confidence Interval	() 90%; -8.0 to 32.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 12.3
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in CDAI-100 response rate for the 200-mg arm at Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2622
	Comments
	Method	GLMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	7.4
	Confidence Interval	(2-Sided) 90%; -11.8 to 26.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 11.7
	Estimation Comments

11. Secondary Outcome

Title	Change From Baseline in CDAI Score Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	PF-04236921 10 mg	PF-04236921 50 mg
Arm/Group Description	Placebo administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 10 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 50 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.
Measure Participants	69	65	71
Week 2 (n=64, 63, 65)	-18.9	-28.4	-16.2
Week 4 (n=66, 58, 59)	-25.1	-37.1	-50.7
Week 6 (n=58, 53, 60)	-32.6	-48.5	-54.9
Week 8 (n=58, 53, 56)	-34.6	-49.6	-63.5
Week 10 (n=54, 50, 51)	-19.8	-50.0	-64.7
Week 12 (n=57, 52, 54)	-27.3	-44.2	-66.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in change from baseline in CDAI score for the 10-mg arm at Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2173
	Comments
	Method	Linear mixed model (LMM)
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.6
	Confidence Interval	(2-Sided) 90%; -29.8 to 10.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 12.22
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in change from baseline in CDAI score for the 10-mg arm at Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1778
	Comments
	Method	LMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-12.0
	Confidence Interval	(2-Sided) 90%; -33.4 to 9.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 12.95
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in change from baseline in CDAI score for the 10-mg arm at Week 6.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1661
	Comments
	Method	LMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-15.9
	Confidence Interval	(2-Sided) 90%; -43.0 to 11.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 16.37
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in change from baseline in CDAI score for the 10-mg arm at Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1993
	Comments
	Method	LMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-14.9
	Confidence Interval	(2-Sided) 90%; -44.1 to 14.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 17.66
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in change from baseline in CDAI score for the 10-mg arm at Week 10.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0632
	Comments
	Method	LMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-30.2
	Confidence Interval	(2-Sided) 90%; -62.7 to 2.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 19.66
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in change from baseline in CDAI score for the 10-mg arm at Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1975
	Comments
	Method	LMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-16.8
	Confidence Interval	(2-Sided) 90%; -49.4 to 15.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 19.71
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments	LSM difference from placebo in change from baseline in CDAI score for the 50-mg arm at Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5868
	Comments
	Method	LMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.7
	Confidence Interval	(2-Sided) 90%; -17.6 to 22.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 12.25
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments	LSM difference from placebo in change from baseline in CDAI score for the 50-mg arm at Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0243
	Comments
	Method	LMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-25.7
	Confidence Interval	(2-Sided) 90%; -47.0 to -4.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 12.93
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments	LSM difference from placebo in change from baseline in CDAI score for the 50-mg arm at Week 6.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0834
	Comments
	Method	LMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-22.4
	Confidence Interval	(2-Sided) 90%; -49.0 to 4.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 16.12
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments	LSM difference from placebo in change from baseline in CDAI score for the 50-mg arm at Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0499
	Comments
	Method	LMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-28.8
	Confidence Interval	(2-Sided) 90%; -57.7 to -0.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 17.43
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments	LSM difference from placebo in change from baseline in CDAI score for the 50-mg arm at Week 10.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0111
	Comments
	Method	LMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-44.9
	Confidence Interval	(2-Sided) 90%; -77.1 to -12.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 19.45
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 50 mg
	Comments	LSM difference from placebo in change from baseline in CDAI score for the 50-mg arm at Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0221
	Comments
	Method	LMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-39.5
	Confidence Interval	(2-Sided) 90%; -71.7 to -7.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 19.49
	Estimation Comments

12. Secondary Outcome

Title	Change From Baseline in CDAI Score Over Time in Participants Who Received Placebo and PF-04236921 200 mg
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	PF-04236921 200 mg
Arm/Group Description	Placebo administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 200 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.
Measure Participants	69	40
Week 2 (n=64, 36)	-21.3	-30.1
Week 4 (n=66, 35)	-26.6	-30.5
Week 6 (n=58, 32)	-36.7	-42.2
Week 8 (n=58, 29)	-39.1	-48.1
Week 10 (n=54, 29)	-26.3	-56.1
Week 12 (n=57, 29)	-35.2	-66.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in change from baseline in CDAI score for the 200-mg arm at Week 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3157
	Comments
	Method	LMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.8
	Confidence Interval	(2-Sided) 90%; -39.0 to 21.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 18.27
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in change from baseline in CDAI score for the 200-mg arm at Week 4.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4171
	Comments
	Method	LMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.8
	Confidence Interval	(2-Sided) 90%; -34.0 to 26.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 18.28
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in change from baseline in CDAI score for the 200-mg arm at Week 6.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3837
	Comments
	Method	LMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.6
	Confidence Interval	(2-Sided) 90%; -36.6 to 25.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 18.79
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in change from baseline in CDAI score for the 200-mg arm at Week 8.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3204
	Comments
	Method	LMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.0
	Confidence Interval	(2-Sided) 90%; -40.8 to 22.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 19.27
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in change from baseline in CDAI score for the 200-mg arm at Week 10.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0649
	Comments
	Method	LMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-29.9
	Confidence Interval	(2-Sided) 90%; -62.3 to 2.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 19.64
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, PF-04236921 10 mg
	Comments	LSM difference from placebo in change from baseline in CDAI score for the 200-mg arm at Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0598
	Comments
	Method	LMM
	Comments	Status of anti-TNF experience, concomitant immunosuppressant therapy, and baseline were included as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-31.0
	Confidence Interval	(2-Sided) 90%; -63.9 to 1.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 19.87
	Estimation Comments

13. Secondary Outcome

Title	Percentages of Participants With Confirmed Positive Anti-drug Antibodies (ADAs)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-04236921 10 mg	PF-04236921 50 mg	PF-04236921 200 mg
Arm/Group Description	PF-04236921 10 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 50 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 200 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.
Measure Participants	67	71	40
Day 1 (n=56, 66, 36)	0.0 0%	0.0 0%	0.0 0%
Week 4 (n=58, 62, 29)	0.0 0%	1.6 2.4%	0.0 0%
Week 8 (n=53, 53, 27)	0.0 0%	0.0 0%	0.0 0%
Week 12 (n=46, 49, 24)	0.0 0%	0.0 0%	0.0 0%
Week 16 (n=2, 1, 0)	0.0 0%	0.0 0%	NA NaN
Week 24 (n=2, 1, 0)	0.0 0%	0.0 0%	NA NaN
Week 32 (n=1, 0, 0)	0.0 0%	NA NaN	NA NaN
Week 40 (n=2, 1, 0)	0.0 0%	0.0 0%	NA NaN

14. Secondary Outcome

Title	Percentages of Participants With Confirmed Positive Neutralizing Antibodies (NAbs)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-04236921 10 mg	PF-04236921 50 mg	PF-04236921 200 mg
Arm/Group Description	PF-04236921 10 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 50 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 200 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.
Measure Participants	67	71	40
Day 1 (n=56, 66, 36)	0.0 0%	0.0 0%	0.0 0%
Week 4 (n=58, 62, 29)	0.0 0%	1.6 2.4%	0.0 0%
Week 8 (n=53, 53, 27)	0.0 0%	0.0 0%	0.0 0%
Week 12 (n=46, 49, 24)	0.0 0%	0.0 0%	0.0 0%
Week 16 (n=2, 1, 0)	0.0 0%	0.0 0%	NA NaN
Week 24 (n=2, 1, 0)	0.0 0%	0.0 0%	NA NaN
Week 32 (n=1, 0, 0)	0.0 0%	NA NaN	NA NaN
Week 40 (n=2, 1, 0)	0.0 0%	0.0 0%	NA NaN

15. Secondary Outcome

Title	Serum PF-04236921 Concentration Over Time
Time Frame	Day 1 (predose), and at Weeks 2, 4 (Day 28, predose), 8, 10, 12, 16, 20, 24, 28, 32, 36, and 40

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	PF-04236921 10 mg	PF-04236921 50 mg	PF-04236921 200 mg
Arm/Group Description	PF-04236921 10 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 50 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 200 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.
Measure Participants	65	71	40
Day 1 (n=54, 64, 37)	4.52 (33.20)	2.05 (16.38)	NA (NA)
Week 2 (n=46, 56, 30)	1060 (531.3)	4580 (1938)	21300 (9547)
Week 4 (n=56, 63, 29)	674 (339.3)	3180 (1555)	14800 (6641)
Week 6 (n=48, 57, 28)	1470 (863.0)	6610 (2668)	32200 (13240)
Week 8 (n=51, 52, 28)	992 (501.7)	4500 (1993)	20200 (8683)
Week 10 (n=47, 54, 29)	695 (428.5)	3280 (1961)	13600 (7350)
Week 12 (n=43, 51, 26)	504 (435.5)	2110 (1333)	10900 (7802)
Week 16 (n=2, 1, 0)	177 (250.3)	1290 (NA)	NA (NA)
Week 20 (n=2, 1, 0)	102 (143.5)	425 (NA)	NA (NA)
Week 24 (n=2, 1, 0)	63.5 (89.80)	NA (NA)	NA (NA)
Week 28 (n=2, 0, 0)	NA (NA)	NA (NA)	NA (NA)
Week 32 (n=2, 0, 0)	NA (NA)	NA (NA)	NA (NA)
Week 36 (n=2, 1, 0)	NA (NA)	109 (NA)	NA (NA)
Week 40 (n=2, 1, 0)	NA (NA)	NA (NA)	NA (NA)

16. Secondary Outcome

Title	Number of Participants Who Withdrew From the Study Due to Treatment-emergent Adverse Events (AEs)
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	PF-04236921 10 mg	PF-04236921 50 mg	PF-04236921 200 mg
Arm/Group Description	Placebo administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 10 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 50 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.	PF-04236921 200 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.
Measure Participants	69	67	71	40
Induction period (Weeks 0 to 12)	7 10.1%	6 9%	6 8.5%	8 20%
Follow-up period (after Week 12)	0 0%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	The reporting period was from the time of the first dose of study treatment through last subject visit up to 40 weeks post the first dose of study treatment for serious adverse events (SAEs) and other adverse events (AEs).
Adverse Event Reporting Description	The same event may appear as both an AE and an 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.
Arm/Group Title	Placebo		PF-04236921 10 mg		PF-04236921 50 mg		PF-04236921 200 mg
Arm/Group Description	Placebo administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.		PF-04236921 10 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.		PF-04236921 50 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.		PF-04236921 200 mg administered SC in the anterolateral right and left thighs on Day 1 and Day 28. Each participant received 2 injections due to the double-dummy design of the study.
All Cause Mortality
	Placebo		PF-04236921 10 mg		PF-04236921 50 mg		PF-04236921 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		PF-04236921 10 mg		PF-04236921 50 mg		PF-04236921 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/69 (15.9%)		11/67 (16.4%)		12/71 (16.9%)		11/40 (27.5%)
Ear and labyrinth disorders
Vertigo positional	0/69 (0%)		0/67 (0%)		1/71 (1.4%)		0/40 (0%)
Gastrointestinal disorders
Abdominal pain	0/69 (0%)		2/67 (3%)		0/71 (0%)		0/40 (0%)
Anal fistula	0/69 (0%)		0/67 (0%)		2/71 (2.8%)		1/40 (2.5%)
Colitis	1/69 (1.4%)		0/67 (0%)		0/71 (0%)		0/40 (0%)
Crohn's disease	6/69 (8.7%)		6/67 (9%)		5/71 (7%)		4/40 (10%)
Haematochezia	0/69 (0%)		0/67 (0%)		0/71 (0%)		1/40 (2.5%)
Ileal fistula	0/69 (0%)		1/67 (1.5%)		0/71 (0%)		0/40 (0%)
Intestinal perforation	0/69 (0%)		0/67 (0%)		0/71 (0%)		1/40 (2.5%)
Large intestinal stenosis	0/69 (0%)		0/67 (0%)		1/71 (1.4%)		0/40 (0%)
Large intestine perforation	0/69 (0%)		0/67 (0%)		1/71 (1.4%)		0/40 (0%)
Pancreatitis acute	0/69 (0%)		0/67 (0%)		0/71 (0%)		1/40 (2.5%)
General disorders
Chest pain	0/69 (0%)		1/67 (1.5%)		0/71 (0%)		0/40 (0%)
Chills	0/69 (0%)		1/67 (1.5%)		0/71 (0%)		0/40 (0%)
Device occlusion	0/69 (0%)		0/67 (0%)		1/71 (1.4%)		0/40 (0%)
Malaise	1/69 (1.4%)		0/67 (0%)		0/71 (0%)		0/40 (0%)
Pyrexia	1/69 (1.4%)		0/67 (0%)		0/71 (0%)		0/40 (0%)
Infections and infestations
Abscess	1/69 (1.4%)		0/67 (0%)		0/71 (0%)		0/40 (0%)
Anal abscess	0/69 (0%)		1/67 (1.5%)		2/71 (2.8%)		0/40 (0%)
Groin abscess	0/69 (0%)		0/67 (0%)		0/71 (0%)		1/40 (2.5%)
Pneumonia	0/69 (0%)		0/67 (0%)		0/71 (0%)		1/40 (2.5%)
Retroperitoneal abscess	0/69 (0%)		0/67 (0%)		1/71 (1.4%)		0/40 (0%)
Sepsis	1/69 (1.4%)		0/67 (0%)		0/71 (0%)		0/40 (0%)
Abscess intestinal	0/69 (0%)		1/67 (1.5%)		0/71 (0%)		0/40 (0%)
Perirectal abscess	0/69 (0%)		0/67 (0%)		1/71 (1.4%)		0/40 (0%)
Injury, poisoning and procedural complications
Road traffic accident	1/69 (1.4%)		0/67 (0%)		0/71 (0%)		0/40 (0%)
Investigations
Liver function test abnormal	0/69 (0%)		1/67 (1.5%)		0/71 (0%)		0/40 (0%)
Alanine aminotransferase increased	0/69 (0%)		0/67 (0%)		1/71 (1.4%)		0/40 (0%)
Metabolism and nutrition disorders
Malnutrition	0/69 (0%)		0/67 (0%)		1/71 (1.4%)		0/40 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/69 (0%)		1/67 (1.5%)		0/71 (0%)		0/40 (0%)
Fistula	1/69 (1.4%)		0/67 (0%)		0/71 (0%)		0/40 (0%)
Nervous system disorders
Headache	0/69 (0%)		1/67 (1.5%)		0/71 (0%)		0/40 (0%)
VIIth nerve paralysis	1/69 (1.4%)		0/67 (0%)		0/71 (0%)		0/40 (0%)
Renal and urinary disorders
Acute kidney injury	0/69 (0%)		1/67 (1.5%)		0/71 (0%)		0/40 (0%)
Nephrolithiasis	0/69 (0%)		0/67 (0%)		0/71 (0%)		1/40 (2.5%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	0/69 (0%)		0/67 (0%)		1/71 (1.4%)		0/40 (0%)
Pulmonary embolism	0/69 (0%)		0/67 (0%)		1/71 (1.4%)		1/40 (2.5%)
Respiratory failure	0/69 (0%)		0/67 (0%)		1/71 (1.4%)		0/40 (0%)
Vascular disorders
Deep vein thrombosis	0/69 (0%)		0/67 (0%)		0/71 (0%)		1/40 (2.5%)
Other (Not Including Serious) Adverse Events
	Placebo		PF-04236921 10 mg		PF-04236921 50 mg		PF-04236921 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/69 (52.2%)		38/67 (56.7%)		48/71 (67.6%)		20/40 (50%)
Blood and lymphatic system disorders
Anaemia	4/69 (5.8%)		1/67 (1.5%)		2/71 (2.8%)		2/40 (5%)
Gastrointestinal disorders
Abdominal pain	8/69 (11.6%)		6/67 (9%)		8/71 (11.3%)		6/40 (15%)
Abdominal pain upper	0/69 (0%)		1/67 (1.5%)		1/71 (1.4%)		3/40 (7.5%)
Crohn's disease	4/69 (5.8%)		2/67 (3%)		7/71 (9.9%)		4/40 (10%)
Nausea	1/69 (1.4%)		8/67 (11.9%)		7/71 (9.9%)		1/40 (2.5%)
Proctalgia	0/69 (0%)		2/67 (3%)		5/71 (7%)		0/40 (0%)
Vomiting	2/69 (2.9%)		4/67 (6%)		5/71 (7%)		2/40 (5%)
General disorders
Fatigue	0/69 (0%)		2/67 (3%)		4/71 (5.6%)		0/40 (0%)
Pyrexia	7/69 (10.1%)		5/67 (7.5%)		5/71 (7%)		1/40 (2.5%)
Infections and infestations
Nasopharyngitis	3/69 (4.3%)		11/67 (16.4%)		8/71 (11.3%)		3/40 (7.5%)
Upper respiratory tract infection	2/69 (2.9%)		0/67 (0%)		4/71 (5.6%)		0/40 (0%)
Urinary tract infection	3/69 (4.3%)		4/67 (6%)		3/71 (4.2%)		5/40 (12.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	8/69 (11.6%)		5/67 (7.5%)		5/71 (7%)		0/40 (0%)
Back pain	4/69 (5.8%)		4/67 (6%)		3/71 (4.2%)		1/40 (2.5%)
Pain in extremity	4/69 (5.8%)		2/67 (3%)		1/71 (1.4%)		1/40 (2.5%)
Nervous system disorders
Headache	6/69 (8.7%)		4/67 (6%)		9/71 (12.7%)		2/40 (5%)
Skin and subcutaneous tissue disorders
Erythema	0/69 (0%)		1/67 (1.5%)		5/71 (7%)		1/40 (2.5%)
Rash	1/69 (1.4%)		3/67 (4.5%)		7/71 (9.9%)		1/40 (2.5%)

Limitations/Caveats

Enrollment into the 200 mg arm was halted on 14 August 2013 before reaching the planned sample size due to safety findings in NCT01405196. Hence the 200 mg vs placebo comparisons were excluded from the primary analyses and reported separately.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigators will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.