OPERA II: A Study To Monitor Long-Term Treatment With PF-00547659

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01298492
• Collaborator: (none)
• Enrollment: 268
• Locations: 112
• Arm: 1
• Actual Duration (Months): 60.9
• Patients Per Site: 2.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study provides open-label drug to eligible patients who have completed a prior study of PF-00547659. The primary endpoint for this study is long-term safety.

Condition or Disease	Intervention/Treatment	Phase
Crohn's Disease	Drug: PF-00547659	Phase 2

Detailed Description

The rationale for conducting this open-label extension (OLE) study is primarily to evaluate long term safety of PF 00547659. This protocol also provides the opportunity for continued treatment for subjects responding to treatment from the feeder study. It also provides an opportunity for initial treatment for subjects randomized to placebo in the feeder study. This is a multi center Phase 2, open label, safety extension study for feeder studies which evaluate PF 00546759 in subjects with moderate to severe Crohn's disease. Subjects eligible for this study will have completed the 12 week double blind induction period in study A7281006 and will be stratified by responders or non responders based on change in CDAI in that study, without unblinding treatment assignment from study A7281006. Additionally, subjects who have completed study A7281008 with a clinical response, as defined by that protocol, will also be eligible for this study and treated as "responders". All subjects entering this study must have discontinued immunosuppressant therapy.

Subjects entering this study will be given a 75 mg SC dose at baseline and then every 4 weeks through Week 72. After the active treatment period, the subjects will enter a 24 month follow up period including 6 monthly visits followed by 18 month extended contact (every 6 month telephone contacts). At Week 96, subjects will undergo an End of Study visit but will continue the every 6 month telephone contacts until Week 168.

Study Design

• Study Type: Interventional
• Actual Enrollment: 268 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Primary Purpose: Treatment
• Official Title: A Multicenter Open-label Extension Study To Assess Long-term Safety Of PF-00547659 In Subjects With Crohn's Disease OPERA II
• Actual Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Jul 27, 2016
• Actual Study Completion Date: Jul 27, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Open-Label Treatment Subjects eligible for this study will have completed the 12 week double blind induction period in study A7281006 and will be stratified by responders or non responders based on change in CDAI in that study, without unblinding treatment assignment from study A7281006. Additionally, subjects who have completed study A7281008	Drug: PF-00547659; 75 mg SC once monthly for 72 weeks. Subjects may escalate to 225 mg or de-escalate to 22.5 mg one time.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With On-Treatment Adverse Events (AEs), AEs Led to Withdrawal, and Serious Adverse Events (SAEs) [From start of study treatment up to Week 72 (Treatment Period)]

   AEs included adverse drug reactions, illnesses with onset during the study, exacerbation of previous illnesses, clinically significant changes in physical examination findings and abnormal objective test findings (ECG, laboratory). An SAE was defined as any AE at any dose that resulted in death; was life threatening (immediate risk of death); required in-subject hospitalization or prolongation of existing hospitalization; resulted in a persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); or resulted in congenital anomaly/birth defect.

Secondary Outcome Measures

1. Number of Participants With Positive Anti-Drug (PF-00547659) Antibodies [Baseline up to Week 96]

   Positive Anti-Drug Antibodies result was defined as ADA titre value greater than or equal to (>=) 4.64 at at least one of the time points.

2. Serum Trough Concentrations of PF-00547659 Versus Time [Week 4,8,12,16,20,24,28,32,36,40,44,48,52,56,60,64,68,72,76,80,84,88,92,96]

   Serum trough concentrations of PF-00547659 were analyzed using population Pharmacokinetic (PK) methodology.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Subjects between 18 and 76 years of age.

• Subjects previously enrolled in study A7281006 who have completed the blinded 84 day (12 week) induction period or in study A7281008 who have completed Week 12 and have demonstrated a clinical response as defined by that protocol.

Exclusion Criteria:

• Subjects that have completed Day 84 (Week 12) of a PF-00547659 study but have experienced serious event(s) related to the investigational product, an unstable medical condition, or any other reason, in the opinion of the investigator, would hinder entry or participation in this study.

• Subjects who are taking any dose of azathioprine, 6-mercaptopurine or methotrexate.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSD Medical Center - Thorton Hospital	La Jolla	California	United States	92037
2	Community Clinical Trials	Orange	California	United States	92868
3	GastroDiagnostics	Orange	California	United States	92868
4	Clinical Research of the Rockies	Lafayette	Colorado	United States	80026
5	Rmga - Rmcr	Thornton	Colorado	United States	80229
6	Rocky Mountain Gastroenterology Associates	Thornton	Colorado	United States	80229
7	MGG Group Co., Inc.	Washington	District of Columbia	United States	20006
8	Florida Center for Gastroenterology	Largo	Florida	United States	33777
9	Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
10	University of Miami Crohn's and Colitis Center	Miami	Florida	United States	33136
11	University of Miami Hospital and Clinic (IP Shipment Only)	Miami	Florida	United States	33136
12	University of Miami Hospital and Clinic	Miami	Florida	United States	33136
13	University of Miami Hospital	Miami	Florida	United States	33136
14	Citrus Ambulatory Surgery Center	Orlando	Florida	United States	32806
15	Internal Medicine Specialists	Orlando	Florida	United States	32806
16	Heartland Medical Research, Inc.	Clive	Iowa	United States	50325
17	Iowa Digestive Disease Center	Clive	Iowa	United States	50325
18	Iowa Endoscopy Center (Colonoscopy Only)	Clive	Iowa	United States	50325
19	Metropolitan Gastroenterology Group, PC - Chevy Chase Clinical Research	Chevy Chase	Maryland	United States	20815
20	UMass Memorial Medical Center	Worcester	Massachusetts	United States	01655
21	University of Massachusetts Worcester	Worcester	Massachusetts	United States	01655
22	Center for Digestive Health	Troy	Michigan	United States	48098
23	Surgical Centers of Michigan	Troy	Michigan	United States	48098
24	Surgery Center of Columbia	Columbia	Missouri	United States	65201
25	Audrain Medical Center	Mexico	Missouri	United States	65265
26	Center for Digestive and Liver Diseases, Inc.	Mexico	Missouri	United States	65265
27	Barnes-Jewish Hospital - Investigational Drug Services	Saint Louis	Missouri	United States	63108
28	Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
29	Center for Advanced Medicine	Saint Louis	Missouri	United States	63110
30	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
31	Albany Medical College	Albany	New York	United States	12208
32	New York Hospital Queens	Flushing	New York	United States	11355
33	Long Island Clinical Research Associates, LLP	Great Neck	New York	United States	11021
34	Nassau Gastroenterology Associates Office Based Surgery	Great Neck	New York	United States	11021
35	Nassau Gastroenterology Associates, P.C.	Great Neck	New York	United States	11021
36	North Shore Primary Care, P.C.	Great Neck	New York	United States	11021
37	Lenox Hill Endoscopy Center	New York	New York	United States	10075
38	Synergy First	New York	New York	United States	11230
39	Premier Medical Group of the Hudson Valley, PC	Poughkeepsie	New York	United States	12601
40	CTRC Hospital, UNC Memorial Hospital	Chapel Hill	North Carolina	United States	27514
41	North Carolina Memorial Hospital Endoscopy Center	Chapel Hill	North Carolina	United States	27514
42	UNC Hospitals	Chapel Hill	North Carolina	United States	27514
43	UNC Hospitals Endoscopy	Chapel Hill	North Carolina	United States	27517
44	Hillsborough Campus	Hillsborough	North Carolina	United States	27278
45	University of Washington Medical Center	Seattle	Washington	United States	98195
46	University of Washington	Seattle	Washington	United States	98195
47	Allegiance Research Specialists	Wauwatosa	Wisconsin	United States	53226
48	AKH Wien Universitaetsklinik fuer Innere Medizin III	Wien		Austria	1090
49	AKH Wien	Wien		Austria	1090
50	Hospital Erasme	Brussels		Belgium	B-1070
51	UZ Gasthuisberg - Pharmacy	Leuven		Belgium	B-3000
52	UZ Gasthuisberg	Leuven		Belgium	B-3000
53	Centre Hospitalier Universitaire De Liege-Domaine Universitaire du Sart Tilman	Liege		Belgium	4000
54	Centre Hospitalier de Mouscron	Mouscron		Belgium	7700
55	Oshawa Clinic	Oshawa	Ontario	Canada	L1H 1B9
56	Toronto Digestive Disease Associates Inc.	Vaughan	Ontario	Canada	L4L 4Y7
57	Hopital Beaujon	Clichy		France	92110
58	Hopital Huriez, CHRU de Lille	Lille Cedex		France	59037
59	CHRU de Lille, Pharamcie Centrale	Lille		France	59037
60	CIC - Hopital Cardiologique	Lille		France	59037
61	Hopital de l'Archet 2 - CHU de Nice	NICE Cedex 3		France	06202
62	Hopital Saint-Louis	Paris		France	75010
63	Hopital Nord	St Priest En Jarez		France	42270
64	Hopital Rangueil	Toulouse Cedex 9		France	31059
65	Robert Bosch Krankenhaus GmbH	Stuttgart	Baden-wuerttemberg	Germany	70376
66	Universitaetsklinikum Ulm	Ulm	Baden-wuerttemberg	Germany	89081
67	"Charite - Campus Berlin Mitte Medizinische Klinik	Berlin		Germany	10117
68	Charite, Universitaetsmedizin Berlin, Campus Virchow-Klinikum	Berlin		Germany	13353
69	Krankenhaus Martha-Maria Halle-Doelau gGmbH	Halle		Germany	06120
70	Universitaetsklinikum Schleswig-Holstein, Campus Kiel	Kiel		Germany	24105
71	Universitaetsfrauenklinikum Schleswig-Holstein	Luebeck		Germany	23538
72	Gastroenterologische Gemeinschaftspraxis Minden	Minden		Germany	32423
73	Universitaetsklinik Regensburg	Regensburg		Germany	93042
74	National Hospital Organization Takasaki General Medical Center	Takasaki	Gunma	Japan	370-0829
75	Yokohama City University Medical Center	Yokohama-Shi	Kanagawa	Japan	232-0024
76	The Jikei University Hospital	Minato-Ku	Tokyo	Japan	105-8471
77	Keio University Hospital	Shinjuku-Ku	Tokyo	Japan	160-8582
78	National Hospital Organization Hirosaki National Hospital	Aomori	Toyko	Japan	036-8545
79	Chiba University Hospital	Chiba		Japan	260-8677
80	Pusan National University Hospital	Busan		Korea, Republic of	602-739
81	Yeungnam University Hospital	Daegu		Korea, Republic of	705-717
82	Samsung Medical Center	Seoul		Korea, Republic of	06351
83	Kangbuk Samsung Hospital	Seoul		Korea, Republic of	110-746
84	Samsung Medical Center	Seoul		Korea, Republic of	135-710
85	Asan Medical Center	Seoul		Korea, Republic of	138-736
86	Academic Medical Center	Amsterdam		Netherlands	1105 AZ
87	University Medical Center Groningen	Groningen		Netherlands	9713GZ
88	Maastricht University Medical Center	Maastricht		Netherlands	6229 HX
89	Sykehusapoteket Asker og Baerum	Gjettum		Norway	1346
90	Oslo Universitetssykehus	Oslo		Norway	0424
91	Lovisenberg Diakonale Sykehus	Oslo		Norway	0440
92	Vestre Viken HF	Rud		Norway	1309
93	Centrum Endoskopii Zabiegowej	Bydgoszcz		Poland	85-168
94	NZOZ Centrum Medyczne Szpital Sw. Rodziny	Lodz		Poland	90-302
95	Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych i Administracji w Warszawie	Warszawa		Poland	02-507
96	Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych W Warszawie	Warszawa		Poland	02-507
97	Lexmedica	Wroclaw		Poland	53-114
98	Military Medical Academy	Belgrade		Serbia	11000
99	Clinical Hospital Centre Bezanijska Kosa	Belgrade		Serbia	11080
100	Clinical Hospital Center Zemun, Clinical Department for Gastroenterology and Hepatology	Zemun		Serbia	11080
101	Gastroentero-Hepatologicke centrum THALION, LAMA MEDICAL CARE s.r.o.	Bratislava		Slovakia	831 04
102	Medak s.r.o.	Bratislava		Slovakia	851 01
103	KM Management spol. s r.o.	Nitra		Slovakia	949 01
104	Synergy group, a.s.	Nove Mesto nad Vahom		Slovakia	915 01
105	Wits Clinical Research	Johannesburg	Gauteng, South Africa	South Africa	2193
106	Parklands Medical Centre	Durban	KWA ZULU Natal	South Africa	4091
107	Kingsbury Hospital	Cape Town	Western CAPE	South Africa	7708
108	Corporacio Sanitaria Parc Tauli de Sabadell	Sabadell	Barcelona	Spain	08208
109	Corporacio Sanitaria Parc Tauli de Sabadell	Sabadell	Cataluna	Spain	08208
110	Hospital Puerta de Hierro Majadahonda	Majadahonda	Madrid	Spain	28222
111	Hospital Universitario de La Princesa	Madrid		Spain	28006
112	Hospital General Universitario Gregorio Maranon	Madrid		Spain	28007

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Takeda

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: Shire
• ClinicalTrials.gov Identifier: NCT01298492
• Other Study ID Numbers: A7281007; 2010-024638-48
• First Posted: Feb 17, 2011
• Last Update Posted: Jun 3, 2021
• Last Verified: May 1, 2021

• Keywords provided by Shire: Active Crohn's disease; Anti-TNF Refractory; Immunosuppressant Refractory
• Additional relevant MeSH terms: Crohn Disease

Study Results

Participant Flow

Recruitment Details	The study was conducted at 81 centers in Austria, Belgium, Canada, France, Germany, Japan, Netherlands, Norway, Poland, Republic of Korea, Serbia, Slovakia, South Africa, Spain and United States between 22 July 2011 (first participant first visit) and 27 July 2016 (last participant last visit).
Pre-assignment Detail	A total of 268 participants (225 participants from Feeder Study A7281006 [NCT01276509] and 43 participants from Feeder Study A7281008 [NCT01387594]) were enrolled and overall 149 participants completed the study.

Arm/Group Title	PF-00547659 75 mg
Arm/Group Description	Participants received PF-00547659 75 milligram (mg) subcutaneous injection once in every 4 weeks through Week 72. One time dose escalation to 225 mg subcutaneous injection was allowed after 8 weeks of the study for the participants who experienced clinical deterioration or unacceptably low level of response to study drug. One time dose de-escalation to 22.5 mg subcutaneous injection due to intolerance or AEs was also allowed after the investigator carefully assessed the status of the participant.
Period Title: Overall Study
STARTED	268
COMPLETED	149
NOT COMPLETED	119

Baseline Characteristics

Arm/Group Title	PF-00547659 75 mg
Arm/Group Description	Participants received PF-00547659 75 mg subcutaneous injection once in every 4 weeks through Week 72. One time dose escalation to 225 mg subcutaneous injection was allowed after 8 weeks of the study for the participants who experienced clinical deterioration or unacceptably low level of response to study drug. One time dose de-escalation to 22.5 mg subcutaneous injection due to intolerance or AEs was also allowed after the investigator carefully assessed the status of the participant.
Overall Participants	268
Age (year) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [year]	36.5 (11.7)
Sex: Female, Male (Count of Participants)
Female	151 56.3%
Male	117 43.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With On-Treatment Adverse Events (AEs), AEs Led to Withdrawal, and Serious Adverse Events (SAEs)
Description	AEs included adverse drug reactions, illnesses with onset during the study, exacerbation of previous illnesses, clinically significant changes in physical examination findings and abnormal objective test findings (ECG, laboratory). An SAE was defined as any AE at any dose that resulted in death; was life threatening (immediate risk of death); required in-subject hospitalization or prolongation of existing hospitalization; resulted in a persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); or resulted in congenital anomaly/birth defect.
Time Frame	From start of study treatment up to Week 72 (Treatment Period)

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population included all enrolled participants who received at least 1 dose of investigational product.

Arm/Group Title	PF-00547659 75 mg
Arm/Group Description	Participants received PF-00547659 75 mg subcutaneous injection once in every 4 weeks through Week 72. One time dose escalation to 225 mg subcutaneous injection was allowed after 8 weeks of the study for the participants who experienced clinical deterioration or unacceptably low level of response to study drug. One time dose de-escalation to 22.5 mg subcutaneous injection due to intolerance or AEs was also allowed after the investigator carefully assessed the status of the participant.
Measure Participants	268
Participants With AEs	249 92.9%
Participants With AEs Led to Withdrawal	53 19.8%
Participants With SAEs	80 29.9%

2. Secondary Outcome

Title	Number of Participants With Positive Anti-Drug (PF-00547659) Antibodies
Description	Positive Anti-Drug Antibodies result was defined as ADA titre value greater than or equal to (>=) 4.64 at at least one of the time points.
Time Frame	Baseline up to Week 96

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population included all enrolled participants who received at least 1 dose of investigational product.

Arm/Group Title	PF-00547659 75 mg
Arm/Group Description	Participants received PF-00547659 75 mg subcutaneous injection once in every 4 weeks through Week 72. One time dose escalation to 225 mg subcutaneous injection was allowed after 8 weeks of the study for the participants who experienced clinical deterioration or unacceptably low level of response to study drug. One time dose de-escalation to 22.5 mg subcutaneous injection due to intolerance or AEs was also allowed after the investigator carefully assessed the status of the participant.
Measure Participants	268
Count of Participants [Participants]	63 23.5%

3. Secondary Outcome

Title	Serum Trough Concentrations of PF-00547659 Versus Time
Description	Serum trough concentrations of PF-00547659 were analyzed using population Pharmacokinetic (PK) methodology.
Time Frame	Week 4,8,12,16,20,24,28,32,36,40,44,48,52,56,60,64,68,72,76,80,84,88,92,96

Outcome Measure Data

Analysis Population Description

PK population included all enrolled participants who received at least 1 dose of investigational product and had data on at least 1 PK concentration.

Arm/Group Title	PF-00547659 75 mg
Arm/Group Description	Participants received PF-00547659 75 mg subcutaneous injection once in every 4 weeks through Week 72. One time dose escalation to 225 mg subcutaneous injection was allowed after 8 weeks of the study for the participants who experienced clinical deterioration or unacceptably low level of response to study drug. One time dose de-escalation to 22.5 mg subcutaneous injection due to intolerance or AEs was also allowed after the investigator carefully assessed the status of the participant.
Measure Participants	260
Week 4	6673 (6634.2)
Week 8	6064 (4455.3)
Week 12	8040 (6293.1)
Week 16	9563 (7285.4)
Week 20	10400 (8438.6)
Week 24	10450 (7934.6)
Week 28	10780 (9211.0)
Week 32	11920 (10675)
Week 36	12460 (9717.1)
Week 40	12570 (10077)
Week 44	12960 (10999)
Week 48	13170 (11108)
Week 52	13560 (11388)
Week 56	13930 (11191)
Week 60	14130 (11095)
Week 64	14360 (11290)
Week 68	14990 (12883)
Week 72	13910 (10554)
Week 76	10520 (10082)
Week 80	3555 (5339.8)
Week 84	1129 (2634.7)
Week 88	403.8 (1522.6)
Week 92	154.2 (1001.9)
Week 96	54.73 (487.07)

Adverse Events

Time Frame	From Start of Study Treatment up to Safety Follow up (Week 96)
Arm/Group Title	PF-00547659 75 mg
Arm/Group Description	Participants received PF-00547659 75 mg subcutaneous injection once in every 4 weeks through Week 72. One time dose escalation to 225 mg subcutaneous injection was allowed after 8 weeks of the study for the participants who experienced clinical deterioration or unacceptably low level of response to study drug. One time dose de-escalation to 22.5 mg subcutaneous injection due to intolerance or AEs was also allowed after the investigator carefully assessed the status of the participant.
All Cause Mortality
	PF-00547659 75 mg
	Affected / at Risk (%)	# Events
Total	2/268 (0.7%)
Serious Adverse Events
	PF-00547659 75 mg
	Affected / at Risk (%)	# Events
Total	118/268 (44%)
Blood and lymphatic system disorders
Anaemia	1/268 (0.4%)	1
Cardiac disorders
Coronary artery disease	1/268 (0.4%)	1
Myocardial infarction	1/268 (0.4%)	1
Endocrine disorders
Adrenocortical insufficiency acute	1/268 (0.4%)	1
Eye disorders
Visual impairment	1/268 (0.4%)	1
Gastrointestinal disorders
Abdominal hernia obstructive	1/268 (0.4%)	1
Abdominal pain	3/268 (1.1%)	3
Anal fistula	7/268 (2.6%)	7
Anal stenosis	1/268 (0.4%)	1
Colitis	1/268 (0.4%)	1
Colitis ulcerative	1/268 (0.4%)	1
Crohn's disease	44/268 (16.4%)	51
Duodenitis	1/268 (0.4%)	1
Enterocutaneous fistula	1/268 (0.4%)	1
Gastrointestinal disorder	1/268 (0.4%)	1
Ileal stenosis	1/268 (0.4%)	1
Ileus	4/268 (1.5%)	4
Intestinal fistula	1/268 (0.4%)	1
Intestinal haemorrhage	1/268 (0.4%)	1
Intestinal obstruction	2/268 (0.7%)	4
Large intestinal obstruction	1/268 (0.4%)	1
Large intestinal stenosis	1/268 (0.4%)	1
Melaena	1/268 (0.4%)	1
Nausea	3/268 (1.1%)	3
Pancreatitis	1/268 (0.4%)	1
Pancreatitis acute	1/268 (0.4%)	1
Small intestinal obstruction	4/268 (1.5%)	11
Vomiting	3/268 (1.1%)	3
General disorders
General physical health deterioration	1/268 (0.4%)	1
Pyrexia	2/268 (0.7%)	3
Hepatobiliary disorders
Cholecystitis	1/268 (0.4%)	1
Cholecystitis acute	1/268 (0.4%)	1
Cholelithiasis	2/268 (0.7%)	2
Hepatic cyst	1/268 (0.4%)	1
Infections and infestations
Abdominal abscess	2/268 (0.7%)	2
Abdominal wall abscess	2/268 (0.7%)	2
Abscess intestinal	1/268 (0.4%)	1
Abscess neck	1/268 (0.4%)	1
Anal abscess	10/268 (3.7%)	10
Clostridium difficile infection	3/268 (1.1%)	3
Device related infection	1/268 (0.4%)	1
Gastroenteritis	3/268 (1.1%)	3
Gastroenteritis viral	1/268 (0.4%)	1
Liver abscess	1/268 (0.4%)	1
Pelvic abscess	2/268 (0.7%)	2
Perirectal abscess	1/268 (0.4%)	1
Peritonitis	3/268 (1.1%)	3
Pneumonia	4/268 (1.5%)	5
Postoperative abscess	1/268 (0.4%)	1
Rotavirus infection	1/268 (0.4%)	1
Splenic abscess	1/268 (0.4%)	1
Tonsillitis	1/268 (0.4%)	1
Vulval abscess	1/268 (0.4%)	1
Injury, poisoning and procedural complications
Anastomotic leak	1/268 (0.4%)	1
Fracture	1/268 (0.4%)	1
Gastrointestinal stoma complication	1/268 (0.4%)	1
Humerus fracture	2/268 (0.7%)	3
Postoperative ileus	1/268 (0.4%)	1
Stomal hernia	1/268 (0.4%)	1
Upper limb fracture	1/268 (0.4%)	1
Wound dehiscence	1/268 (0.4%)	1
Investigations
Blood creatine phosphokinase mm increased	1/268 (0.4%)	1
Haematocrit decreased	1/268 (0.4%)	1
Metabolism and nutrition disorders
Fluid retention	1/268 (0.4%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/268 (0.4%)	1
Arthritis	1/268 (0.4%)	1
Arthritis enteropathic	1/268 (0.4%)	1
Muscle spasms	1/268 (0.4%)	1
Muscular weakness	1/268 (0.4%)	1
Spinal column stenosis	1/268 (0.4%)	1
Spinal osteoarthritis	1/268 (0.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	1/268 (0.4%)	1
Metastatic neoplasm	1/268 (0.4%)	1
Renal cancer	1/268 (0.4%)	1
Nervous system disorders
Headache	2/268 (0.7%)	2
Intracranial venous sinus thrombosis	1/268 (0.4%)	1
Renal and urinary disorders
Bladder dysfunction	1/268 (0.4%)	1
Nephrolithiasis	2/268 (0.7%)	2
Ureterolithiasis	1/268 (0.4%)	1
Urinoma	1/268 (0.4%)	1
Reproductive system and breast disorders
Female genital tract fistula	1/268 (0.4%)	1
Menorrhagia	1/268 (0.4%)	1
Perineal fistula	1/268 (0.4%)	1
Respiratory, thoracic and mediastinal disorders
Pleural effusion	1/268 (0.4%)	1
Pneumonia aspiration	1/268 (0.4%)	1
Skin and subcutaneous tissue disorders
Pyoderma gangrenosum	1/268 (0.4%)	1
Surgical and medical procedures
Benign breast lump removal	1/268 (0.4%)	1
Other (Not Including Serious) Adverse Events
	PF-00547659 75 mg
	Affected / at Risk (%)	# Events
Total	206/268 (76.9%)
Gastrointestinal disorders
Abdominal pain	49/268 (18.3%)	59
Anal fissure	14/268 (5.2%)	14
Aphthous ulcer	14/268 (5.2%)	18
Crohn's disease	79/268 (29.5%)	111
Diarrhoea	24/268 (9%)	38
Nausea	32/268 (11.9%)	44
Vomiting	23/268 (8.6%)	34
General disorders
Asthenia	15/268 (5.6%)	20
Fatigue	20/268 (7.5%)	23
Pyrexia	27/268 (10.1%)	36
Infections and infestations
Anal abscess	14/268 (5.2%)	16
Bronchitis	20/268 (7.5%)	26
Gastroenteritis	19/268 (7.1%)	22
Influenza	18/268 (6.7%)	19
Nasopharyngitis	54/268 (20.1%)	93
Pharyngitis	15/268 (5.6%)	18
Upper respiratory tract infection	20/268 (7.5%)	25
Urinary tract infection	19/268 (7.1%)	28
Musculoskeletal and connective tissue disorders
Arthralgia	83/268 (31%)	113
Back pain	28/268 (10.4%)	30
Nervous system disorders
Headache	35/268 (13.1%)	45

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Sponsor has the right to review disclosures, requesting a delay of up to 60 days. The first publication must be a joint publication covering all centers. However, if a joint manuscript has not been submitted for publication within 12 months of completion or termination of study at all participating sites, Investigator may publish individual site results separately. Investigator may not disclose previously undisclosed confidential information other than study results.