Safety, Tolerability, PK and PD of SCH 900518 in Naive or Treatment-Experienced Subjects Infected With HCV Genotype 1 (Protocol No. P04695)
Assessment of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SCH 900518 in Naive or Treatment-Experienced Subjects Infected With Hepatitis C Virus Genotype 1 (Protocol No. P04695)
1 other identifier
interventional
41
0 countries
N/A
Brief Summary
Assessment of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SCH 900518 in Naive or Treatment-Experienced Subjects Infected With Hepatitis C Virus Genotype 1 (Protocol No. P04695)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jul 2007
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2008
CompletedFirst Submitted
Initial submission to the registry
March 3, 2010
CompletedFirst Posted
Study publicly available on registry
March 5, 2010
CompletedFebruary 9, 2015
February 1, 2015
1.1 years
March 3, 2010
February 6, 2015
Conditions
Outcome Measures
Primary Outcomes (1)
Safety and tolerability were to be assessed by collecting adverse events (AEs), vital signs, electrocardiograms (ECGs), physical examinations, urinalysis, and safety laboratory tests.
Screening Period: 90 days, Period 1: 7 days, Washout: 4 weeks, Period 2: 14 days, Standard of Care with PegIntron and ribavirin: 84 days
Secondary Outcomes (1)
Log change in HCV-RNA from baseline. Ctrough of SCH 900518 resulting in mean HCV RNA decrease > 2 log10 IU/mL. Ctrough of SCH 900518+PEG resulting in HCV-RNA < LOQ. SCH 900518 PK: Cmax, Tmax, AUC, Ctrough, t½, R, CL/F, Vd/F. PEG and RTV: Ctrough
Period 1: 7 days, Washout: 4 weeks, Period 2: 14 Days
Study Arms (4)
Treatment-naïve 800 mg TID
EXPERIMENTALPeriod 1: SCH 900518 (800 mg TID) or placebo for 7 days Period 2: SCH 900518 (800 mg TID) + PegIntron (1.5 µg/kg QW) or placebo + PegIntron for 14 days.
Treatment-experienced: 800 mg TID
EXPERIMENTALPeriod 1: SCH 900518 (800 mg TID) or placebo for 7 days Period 2: SCH 900518 (800 mg TID) + PegIntron (1.5 ug/kg QW) or placebo + PegIntron for 14 days
Treatment-naïve: 400 mg + RTV BID
EXPERIMENTALPeriod 1: SCH 900518 (400 mg BID) or placebo + RTV (200 mg BID) for 7 days. Period 2: SCH 900518 (400 mg BID) or placebo + RTV (200 mg BID) +PegIntron (1.5 µg/kg QW) for 14 days.
Treatment-experienced: 400 mg + RTV BID
EXPERIMENTALPeriod 1: SCH 900518 (400 mg BID) or placebo + RTV (200 mg BID) for 7 days. Period 2: SCH 900518 (400 mg BID) or placebo + RTV (200 mg BID) +PegIntron (1.5 µg/kg QW) for 14 days.
Interventions
Drug: SCH 900518 Biologic: Peginterferon alfa-2b(PegIntron) Period 1: Amorphous SCH 900518 800 mg or placebo TID administered as an oral suspension for 7 days . Period 2: Amorphous SCH 900518 800 mg or placebo TID administered as an oral suspension for 14 days in combination with 1.5 µg/kg PegIntron administered subcutaneously weekly.
Drug: SCH 900518 Biologic: Peginterferon alfa-2b Period 1: Amorphous SCH 900518 800 mg or placebo TID administered as an oral suspension for 7 days Period 2: Amorphous SCH 900518 800 mg or placebo TID administered as an oral suspension for 14 days in combination with 1.5 µg/kg PegIntron administered subcutaneously weekly.
Drug: SCH 900518 Drug: Ritonavir (RTV) Biologic: Peginterferon alfa-2b (PegIntron) Period 1: Amorphous SCH 900518 (400 mg) or placebo BID administered as oral suspension + ritonavir (200 mg BID) (2-100 mg oral capsules) for 7 days. Period 2: Amorphous SCH 900518 (400 mg) or placebo BID administered as oral suspension+ ritonavir (200 mg BID) (2-100 mg oral capsules) + PegIntron (1.5 µg/kg QW) for 14 days.
Drug: SCH 900518 Drug: Ritonavir (RTV) Biologic: Peginterferon alfa-2b (PegIntron) Period 1, Amorphous SCH 900518 (400 mg) or placebo BID administered as an oral suspension + RTV (200 mg BID) oral capsules (2-100 mg capsules) for 7 days. Period 2, SCH 900518 (400 mg) or placebo BID as an oral suspension + RTV (200 mg BID) oral capsules (2-100 mg capsules) +PegIntron (1.5 µg/kg SC QW) for 14 days.
Eligibility Criteria
You may qualify if:
- Subject infected with HCV genotype 1 (any sub-type) virus who is:
- treatment naïve (eg. to interferon and ribavirin); or
- treatment experienced (non-responder and relapser): subject who received interferon based therapy and continued to have detectable HCV RNA levels at the end of follow-up, a subject who did not attain a 2 log decline in HCV RNA levels at \~12 weeks and discontinued treatment, or subject who had no detectable viral load while on treatment but had a detectable viral load post treatment.
- Subject with acceptable medical history, physical examination, and clinical laboratory evaluations consistent with CHC, compensated liver disease, and any associated diseases (diabetes, hypertension, etc).
- Subjects with an HCV RNA viral load of \>10\^5 copies/mL or equivalent international units
- BMI of 18 to 40 kg/m\^2, men and women, ages 18-65 years inclusive
- Female must be non-lactating and have a negative pregnancy test at Screening and Day -1 and either be of nonchildbearing potential or if of childbearing potential, must be practicing effective double-barrier contraceptive methods from at least 2 weeks prior to Day -1 until 30 days after study completion.
- Male must be willing to practice barrier contraception from Day 1 through 3 months following treatment with SCH 900518.
- Subject must have an ECG recording showing no clinically significant findings at Screening.
- Subject with chronic stable hemophilia may enroll
- Subject on stable methadone treatment may enroll in this study (evaluation by investigator includes history of stable clinical management for \>3 months).
You may not qualify if:
- Subject has a significant acute or chronic medical illness which is not stable or is not controlled with medication (excluding prohibited medications).
- Subject has received an organ transplant.
- Subject has evidence of decompensated liver disease by physical exam (encephalopathy, ascites, caput medusae, etc).
- Subject has at anytime received an HCV NS3-specific protease inhibitor.
- Subject has a platelet count \<80,000/mm\^3 (confirmed by repeat analysis) at Screening.
- Subject has a serum hemoglobin of \<10.0 g/dL (confirmed by repeat analysis) at Screening.
- Subject has a serum AST /ALT value \>5 x ULN (confirmed by repeat analysis) at Screening.
- Subject has a serum alkaline phosphatase value \>2 x ULN (confirmed by repeat analysis) at Screening.
- Two or more of the following criteria (confirmed by repeat analysis) at Screening:
- Total serum bilirubin \>2.0 mg/dL.
- Serum albumin \<3.5 g/dL.
- INR \>1.7 (with the exception of hemophiliacs).
- Subject has a neutrophil count \<1,000/mm\^3 (confirmed by repeat analysis) at Screening.
- Creatinine clearance (as estimated by method of Cockcroft and Gault) less than 50 mL/min at Screening.
- Subject who has a history of any clinically significant local or systemic infectious disease within 1 week prior to screening (other than HCV-infection).
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Related Publications (2)
de Bruijne J, Bergmann JF, Reesink HW, Weegink CJ, Molenkamp R, Schinkel J, Tong X, Li J, Treitel MA, Hughes EA, van Lier JJ, van Vliet AA, Janssen HL, de Knegt RJ. Antiviral activity of narlaprevir combined with ritonavir and pegylated interferon in chronic hepatitis C patients. Hepatology. 2010 Nov;52(5):1590-9. doi: 10.1002/hep.23899.
PMID: 20938912RESULTHotho DM, de Bruijne J, Spaan M, Treitel MA, Boonstra A, de Knegt RJ, Janssen HL, Reesink HW. Sustained virologic response after therapy with the HCV protease inhibitor narlaprevir in combination with peginterferon and ribavirin is durable through long-term follow-up. J Viral Hepat. 2013 Apr;20(4):e78-81. doi: 10.1111/jvh.12012. Epub 2013 Jan 7.
PMID: 23490393RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 3, 2010
First Posted
March 5, 2010
Study Start
July 1, 2007
Primary Completion
August 1, 2008
Study Completion
August 1, 2008
Last Updated
February 9, 2015
Record last verified: 2015-02