Efficacy & Safety of Infliximab Monotherapy Vs Combination Therapy Vs AZA Monotherapy in Ulcerative Colitis (Part 1) Maintenance Vs Intermittent Therapy for Maintaining Remission (Part 2)(Study P04807AM3)(TERMINATED)

This study has been terminated.

( Infusion reactions during re-induction cycles after a period of no treatment in another study [P04563, NCT0358670] )

Study NCT00537316 Information provided by Schering-Plough

First Received on September 28, 2007. Last Updated on November 11, 2011 History of Changes

Results First Received: November 11, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Treatment
Condition:	Ulcerative Colitis
Interventions:	Biological: Infliximab (IFX) Drug: Azathioprine (AZA) Drug: Placebo to Azathioprine Drug: Placebo infusion

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
2 participants were randomized but not treated. Part 1: 237 participants received ≥1 dose study medication. Part 2: Of 108 enrolled/randomized participants, 95 continued assigned treatment from Part 1 and 13 were randomized and entered into Part 2 of the study (10 participants from Part 1 and 3 participants who were enrolled directly into Part 2).

Reporting Groups

	Description
Infliximab (IFX)	IFX 5 mg/kg Intravenous (IV) infusions administered at Weeks 0, 2, and 6 and placebo to AZA (orally) daily for 16 weeks. Responders to IFX at Week 8, will receive one more IFX infusion at Week 14; non-responders to IFX will receive placebo infusions at Weeks 8 and 10 and an additional IFX infusion at Week 14.
Azathioprine (AZA)	AZA 2.5 mg/kg orally for 16 weeks and placebo to IFX infusion at Weeks 0, 2, and 6. Responders to AZA monotherapy at Week 8 will continue on AZA therapy and receive one placebo IFX infusion at Week 14; non-responders to AZA at Week 8 will be eligible to receive IFX at Weeks 8, 10, and 14. This group included 20 participants who did not respond to AZA monotherapy at Week 8 had IFX added to their treatment regimen at Weeks 8, 10, and 14.
IFX/AZA	IFX 5 mg/kg IV infusion at Weeks 0, 2, and 6 plus AZA 2.5 mg/kg orally daily for 16 weeks. Responders to IFX/AZA at Week 8 will receive one more IFX infusion at Week 14; non-responders to IFX/AZA will receive placebo IFX infusions at Weeks 8 and 10 and one additional IFX infusion at Week 14.
Maintenance IFX/AZA (During Part 2)	Participants randomized to maintenance IFX/AZA received IFX 5 mg/kg of body weight every 8 weeks (beginning at Week 22, Week 6 for direct entry) plus AZA 2.5 mg/kg of body weight daily in Part 2 of the study (4 participants from Part 1 of the study and 1 participant was enrolled directly into Part 2 of the study).
Maintenance IFX (During Part 2)	Participants randomized to maintenance IFX received infusion of IFX 5 mg/kg of body weight every 8 weeks (beginning at Week 22, Week 6 for direct entry) and placebo to AZA therapy as allocated in Part 1 of the study (all participants were from Part 1 of the study).
Intermittent IFX/AZA (During Part 2)	Participants randomized to intermittent IFX/AZA received IFX 5 mg/kg of body weight only upon relapse of disease (initiated at Weeks 0, 2, and 6 of individual treatment cycle and continued every 8 weeks until remission was regained) plus AZA 2.5 mg/kg of body weight daily in Part 2 of the study (3 participants from Part 1 of the study and 1 participant was enrolled directly into Part 2 of the study).
Intermittent IFX (During Part 2)	Participants randomized to intermittent IFX received IFX 5 mg/kg of body weight only upon relapse of disease (initiated at Weeks 0, 2, and 6 of individual treatment cycle and continued every 8 weeks until remission was regained) and placebo to AZA as allocated in Part 1 of the study (1 participant from Part 1 of the study and 1 participant was enrolled directly into Part 2 of the study).

Participant Flow for 2 periods

Period 1: Part 1

	Infliximab (IFX)	Azathioprine (AZA)	IFX/AZA
STARTED	79	80	80
COMPLETED	65	53	63
NOT COMPLETED	14	27	17
Adverse Event	7	11	8
Protocol defined clinical event	1	0	0
Lost to Follow-up	1	0	0
Withdrawal by Subject	3	8	4
Protocol Violation	1	5	1
Did not meet protocol eligibility	1	3	2
Administrative	0	0	2

Period 2: Part 2

	Infliximab (IFX)	Azathioprine (AZA)	IFX/AZA	Maintenance IFX/AZA (During Part 2)	Maintenance IFX (During Part 2)	Intermittent IFX/AZA (During Part 2)	Intermittent IFX (During Part 2)
STARTED	37	10	48	5	2	4	2
COMPLETED	11	1	16	2	1	0	0
NOT COMPLETED	26	9	32	3	1	4	2
Never entered follow-up	0	0	0	0	0	0	1
Adverse Event	4	0	2	0	0	0	0
Lost to Follow-up	1	0	2	0	0	0	0
Withdrawal by Subject	5	1	4	0	0	0	0
Administrative	16	8	24	3	1	4	1

Baseline Characteristics

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Reporting Groups

	Description
Infliximab (IFX)	All treated participants. IFX 5 mg/kg IV infusions administered at Weeks 0, 2, and 6 and placebo to AZA daily for 16 weeks. Responders to IFX at Week 8, will receive one more IFX infusion at Week 14; non-responders to IFX will receive placebo infusions at Weeks 8 and 10 and an additional IFX infusion at Week 14.
Azathioprine (AZA)	All treated participants. AZA 2.5 mg/kg orally for 16 weeks and placebo to IFX infusion at Weeks 0, 2, and 6. Responders to AZA monotherapy at Week 8 will continue on AZA therapy and receive one infliximab placebo infusion at Week 14; non-responders to AZA at Week 8 will be eligible to receive infliximab at Weeks 8, 10, and 14. This group included 20 participants who did not respond to AZA monotherapy at Week 8 had IFX added to their treatment regimen at Weeks 8, 10, and 14.
IFX/AZA	All treated participants. IFX 5 mg/kg IV at Weeks 0, 2, and 6 plus AZA 2.5 mg/kg orally daily for 16 weeks. Responders to IFX/AZA at Week 8 will receive one more infliximab infusion at Week 14; non-responders to IFX/AZA will receive placebo IFX infusions at Weeks 8 and 10 and one additional IFX infusion at Week 14.
Maintenance IFX/AZA (During Part 2)	Participants enrolled directly and randomized to maintenance IFX/AZA received IFX 5 mg/kg of body weight every 8 weeks (beginning at Week 22, Week 6 for direct entry) plus AZA 2.5 mg/kg of body weight daily in Part 2 of the study (4 participants from Part 1 of the study and 1 participant enrolled directly into Part 2 of the study).
Intermittent IFX/AZA (During Part 2)	Participants enrolled directly and randomized to intermittent IFX/AZA received IFX 5 mg/kg of body weight only upon relapse of disease (initiated at Weeks 0, 2, and 6 of individual treatment cycle and continued every 8 weeks until remission was regained) plus AZA 2.5 mg/kg of body weight daily in Part 2 of the study (3 participants from Part 1 of the study and 1 participant enrolled directly into Part 2 of the study).
Intermittent IFX (During Part 2)	Participants enrolled directly and randomized to intermittent IFX received IFX 5 mg/kg of body weight only upon relapse of disease (initiated at Weeks 0, 2, and 6 of individual treatment cycle and continued every 8 weeks until remission was regained) and placebo to AZA daily in Part 2 of the study (1 participant from Part 1 of the study and 1 participant enrolled directly into Part 2 of the study).

Baseline Measures

	Infliximab (IFX)	Azathioprine (AZA)	IFX/AZA	Maintenance IFX/AZA (During Part 2)	Intermittent IFX/AZA (During Part 2)	Intermittent IFX (During Part 2)	Total
Number of Participants [units: participants]	78	79	80	1	1	1	240
Age, Customized ^[1] [units: Participants]
<18 years	0	0	0	0	0	0	0
18 years to <65 years	77	76	78	1	1	1	234
65 years and older	1	3	2	0	0	0	6
Gender ^[1] [units: participants]
Female	36	46	32	0	1	1	116
Male	42	33	48	1	0	0	124

[1]	Baseline characteristics for Part 2 are presented for the direct entry participants only: 1 participant randomized to the maintenance IFX/AZA group, 1 participant randomized to the intermittent IFX/AZA group, and 1 participant randomized to the intermittent IFX group. No participants were directly enrolled into the maintenance IFX group in Part 2 of the study.

Outcome Measures

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1. Primary:

Proportion of Participants in Steroid-free Remission at Week 16 [ Time Frame: 16 weeks ]

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2. Secondary:

Proportion of Participants in Response at Weeks 8 and 16 [ Time Frame: Weeks 8 and 16 ]

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3. Secondary:

Proportion of Participants With Mucosal Healing at Week 16 [ Time Frame: 16 weeks ]

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4. Primary:

Average Remission Rate During Part 2 of the Study [ Time Frame: up to Week 94 (Week 78 for direct entry) ]

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

5. Secondary:

Proportion of Participants Who Are in Steroid-free Remission During Part 2 of the Study [ Time Frame: Weeks 38, 62 & 94 (Weeks 22, 46 and 78 for direct entry) ]

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

6. Secondary:

Proportion of Participants With Mucosal Healing During Part 2 of the Study [ Time Frame: Weeks 38, 62 and 94 (Weeks 22, 46 and 78 for direct entry) ]

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The only disclosure restriction on the PI is that the sponsor can review results communications prior to release and can embargo communications regarding trial results for a period that is less than or equal to 45 days from the time submitted to the sponsor for review. If the parties disagree on the communication, the investigator and sponsor's representative will meet for the purpose of making a good faith effort to discuss and resolve any such issues or disagreement.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: Vice President, Late Stage Development Group Leader
Organization: Merck Sharp & Dohme Corp
e-mail: ClinicalTrialsDisclosure@merck.com

No publications provided

Responsible Party:	Schering-Plough
ClinicalTrials.gov Identifier:	NCT00537316 History of Changes
Other Study ID Numbers:	P04807
Study First Received:	September 28, 2007
Results First Received:	November 11, 2011
Last Updated:	November 11, 2011
Health Authority:	Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment