Boceprevir (SCH 503034) Plus Peg-Intron, With and Without Added Ribavirin, in Patients With Chronic Hepatitis C, Genotype 1, Who Did Not Respond to Previous Treatment With Peginterferon Alfa Plus Ribavirin (Study P03659AM2)(COMPLETED)

This study has been completed.

Study NCT00160251 Information provided by Schering-Plough

First Received on September 8, 2005. Last Updated on November 23, 2011 History of Changes

Results First Received: May 13, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double-Blind; Primary Purpose: Treatment
Condition:	Chronic Hepatitis C
Interventions:	Drug: Boceprevir (BOC) Biological: PegIntron (PEG) Drug: Ribavirin (RBV)

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
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Reporting Groups

	Description
Arm 1A: PEG + RBV	A single dose of PEG was given first, followed 1 week A single dose of PEG was given first, followed 1 week later by PEG + RBV + BOC 400. By protocol amendment 2, participants were rolled over into Arm 8 for the remainder of the treatment period.
Arm 1B: PEG + RBV + BOC	A single dose of PEG was given first, followed 1 week later by PEG + RBV for 12 weeks. If HCV-RNA was detectable, BOC 400 was added for another 36 weeks. By protocol amendment 2, participants were rolled over into Arm 8 for the remainder of the treatment period.
Arm 2: PEG + BOC 100 (48 Weeks)	A single dose of PEG was given first, followed 1 week later by PEG + BOC 100 for 48 weeks. By protocol amendment 2, participants were rolled over into Arm 8 for the remainder of the treatment period.
Arm 3: PEG + BOC 200 (48 Weeks)	A single dose of PEG was given first, followed 1 week later by PEG + BOC 200 for 48 weeks. By protocol amendment 2, participants were rolled over into Arm 8 for the remainder of the treatment period.
Arm 5: PEG + RBV + BOC 400	A single dose of PEG was given first, followed 1 week A single dose of PEG was given first, followed 1 week later by PEG + RBV + BOC 400. By protocol amendment 2, participants were rolled over into Arm 8 for the remainder of the treatment period.
ARM 4+6: PEG + BOC 400 (24 + 48 Weeks)	A single dose of PEG was given first, followed 1 week A single dose of PEG was given first, followed 1 week later by PEG + RBV + BOC 400. By protocol amendment 2, participants were rolled over into Arm 8 for the remainder of the treatment period.
Arm 7: PEG + BOC 800	A single dose of PEG was given first, followed 1 week later by PEG + BOC 800. By protocol amendment 2, participants were rolled over into Arm 8 for the remainder of the treatment period.
Arm 8: PEG + RBV + BOC 800	By protocol amendment 2, participants from all arms except Arm 1A were rolled over into PEG + RBV + BOC 800 for the remainder of the treatment period.

Participant Flow for 2 periods

Period 1: Prior to Amendment 2

	Arm 1A: PEG + RBV	Arm 1B: PEG + RBV + BOC	Arm 2: PEG + BOC 100 (48 Weeks)	Arm 3: PEG + BOC 200 (48 Weeks)	Arm 5: PEG + RBV + BOC 400	ARM 4+6: PEG + BOC 400 (24 + 48 Weeks)	Arm 7: PEG + BOC 800
STARTED	15	34	48	49	49	97	65
COMPLETED	6	28	4	9	21	14	61
NOT COMPLETED	9	6	44	40	28	83	4
Adverse Event	2	1	3	1	1	1	1
Lack of Efficacy	0	4	37	35	24	55	0
Lost to Follow-up	0	0	1	0	1	1	0
Withdrawal by Subject	3	1	3	4	2	3	3
Noncompliance with protocol	1	0	0	0	0	0	0
Completed Treatment Phase	3	0	0	0	0	23	0

Period 2: Post-amendment 2

	Arm 1A: PEG + RBV	Arm 1B: PEG + RBV + BOC	Arm 2: PEG + BOC 100 (48 Weeks)	Arm 3: PEG + BOC 200 (48 Weeks)	Arm 5: PEG + RBV + BOC 400	ARM 4+6: PEG + BOC 400 (24 + 48 Weeks)	Arm 7: PEG + BOC 800	Arm 8: PEG + RBV + BOC 800
STARTED	0	0	0	0	0	0	0	143
COMPLETED	0	0	0	0	0	0	0	88
NOT COMPLETED	0	0	0	0	0	0	0	55
Adverse Event	0	0	0	0	0	0	0	20
Lack of Efficacy	0	0	0	0	0	0	0	24
Lost to follow-up/withdrawal by subject	0	0	0	0	0	0	0	11

Baseline Characteristics

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Reporting Groups

	Description
Arm 1A: PEG + RBV OR Arm 1B: PEG + RBV + BOC 400	Arm 1A: A single dose of PEG was given first, followed 1 week later by PEG + RBV for 12 weeks. If participant was HCV-RNA negative, PEG + RBV was continued for another 36 weeks. Arm 1B: A single dose of PEG was given first, followed 1 week later by PEG + RBV for 12 weeks. If HCV-RNA was detectable, BOC 400 was added for another 36 weeks. By protocol amendment 2, participants were rolled over into Arm 8 for the remainder of the treatment period.
Arm 2: PEG + BOC 100 (48 Weeks)	A single dose of PEG was given first, followed 1 week later by PEG + BOC 100 for 48 weeks. By protocol amendment 2, participants were rolled over into Arm 8 for the remainder of the treatment period.
Arm 3: PEG + BOC 200 (48 Weeks)	A single dose of PEG was given first, followed 1 week later by PEG + BOC 200 for 48 weeks. By protocol amendment 2, participants were rolled over into Arm 8 for the remainder of the treatment period.
Arm 5: PEG + RBV + BOC 400	A single dose of PEG was given first, followed 1 week later by PEG + RBV + BOC 400. By protocol amendment 2, participants were rolled over into Arm 8 for the remainder of the treatment period.
Arms 4 + 6: PEG + BOC 400 (24 + 48 Weeks)	A single dose of PEG was given first, followed 1 week later by PEG + BOC (24 or 48 weeks). By protocol amendment 2, participants were rolled over into Arm 8 for the remainder of the treatment period.
Arm 7: PEG + BOC 800	A single dose of PEG was given first, followed 1 week later by PEG + BOC 800. By protocol amendment 2, participants were rolled over into Arm 8 for the remainder of the treatment period.

Baseline Measures

	Arm 1A: PEG + RBV OR Arm 1B: PEG + RBV + BOC 400	Arm 2: PEG + BOC 100 (48 Weeks)	Arm 3: PEG + BOC 200 (48 Weeks)	Arm 5: PEG + RBV + BOC 400	Arms 4 + 6: PEG + BOC 400 (24 + 48 Weeks)	Arm 7: PEG + BOC 800	Total
Number of Participants [units: participants]	49	48	49	49	97	65	357
Age [units: years] Mean ± Standard Deviation	48.9 ± 9.7	51.6 ± 7.0	48.6 ± 9.4	48.2 ± 8.9	49.2 ± 8.7	50.4 ± 7.3	49.5 ± 8.6
Gender [units: participants]
Female	17	21	14	21	37	24	134
Male	32	27	35	28	60	41	223

Outcome Measures

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1. Primary:

Percent of Participants Who Were Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Negative at the End of Treatment (EoT) [ Time Frame: Baseline up to Week 49 ]

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2. Primary:

Percent of Participants Who Achieved Sustained Virologic Response (SVR) [ Time Frame: Baseline up to Week 73 [24 weeks after end of treatment (EoT)] ]

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3. Secondary:

Percent of Participants Who Achieved Sustained Viral Response (SVR) by Time to First Negative HCV-RNA [ Time Frame: Baseline up to Week 73 [24 weeks after EoT] ]

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4. Secondary:

Percentage of Participants Who Were HCV-RNA Negative at EoT After Receiving 1 Week of Treatment With PegIntron (PEG) by Log Drop [ Time Frame: Week 1 and Week 49 ]

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5. Secondary:

Percent of Participants With Virologic Response Prior to Amendment 2 [ Time Frame: Week 3, Week 5, Week 13 ]

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6. Secondary:

Peak Plasma Concentration of Boceprevir (BOC) [ Time Frame: All visits during treatment (baseline to Week 49) except Day 1 of Week 1 ]

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7. Secondary:

Area Under the Plasma Concentration-time Curve of Boceprevir Plasma Concentration for an 8-hour Dosing Period [ Time Frame: All visits during treatment (baseline to Week 49) except Day 1 of Week 1 ]

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8. Secondary:

Trough Plasma Concentration Level [ Time Frame: All visits during treatment (baseline to Week 49) except Day 1 of Week 1 ]

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9. Secondary:

Change in Alanine Aminotransferase (ALT) Levels [ Time Frame: Baseline up to dosing change (> 25 weeks) ]

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10. Secondary:

Number of Participants Who Were HCV-RNA Negative During Amendment 2 (AM2) for Those Who Started on Arms 2 (PEG+BOC 100), 3 (PEG+BOC 200), 4 (PEG+BOC 400 [48 Weeks]), 6 (PEG+BOC 400 [24 Weeks]) [ Time Frame: From dosing change to end of follow-up (Week 73)(up to 48 weeks) ]

Show Outcome Measure 10

11. Secondary:

Number of Participants Who Were HCV-RNA Negative During Amendment 2 (AM2) for Those Who Started on PegIntron (PEG) + Rebetol (RVB) + Boceprevir (BOC) 400 (Arm 5) [ Time Frame: From dosing change to end of follow-up (Week 73)(up to 48 weeks) ]

Show Outcome Measure 11

12. Secondary:

Number of Participants Who Were HCV-RNA Negative During Amendment 2 (AM2) for Those Who Started on PegIntron (PEG) + Boceprevir (BOC) 800 (Arm 7) [ Time Frame: From dosing change to end of follow-up (Week 73) (up to 48 weeks) ]

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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 principal investigator (PI) agrees to provide review copies to the sponsor 30 days prior to submission. The sponsor shall have editorial rights and the right to review and comment on the data analysis and presentation with regard to proprietary information, accuracy of information, and to ensure that the presentation is fairly balanced and in compliance with regulations. If the parties disagree, the PI agrees to meet with the sponsor 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
The implementation of amendment 2 led to changes in boceprevir dose in all treatment arms and different overall lengths of therapy within the same treatment arm, making the SVR endpoint uninterpretable.

Results Point of Contact:

Name/Title: Vice President, Late Stage Development Group Leader
Organization: Schering-Plough
e-mail: ClinicalTrialsDisclosure@merck.com

No publications provided

Responsible Party:	Vice President, Late Stage Development Group Leader, Schering-Plough
ClinicalTrials.gov Identifier:	NCT00160251 History of Changes
Other Study ID Numbers:	P03659
Study First Received:	September 8, 2005
Results First Received:	May 13, 2011
Last Updated:	November 23, 2011
Health Authority:	United States: Food and Drug Administration