Phase 1 Study To Evaluate Antiviral Activity Of Small Molecule Direct Antiviral Agent At Multiple Doses In Subjects With Chronically Infected Hepatitis C Virus.

A Phase 1, Non- Randomized, Open Label, Sequential Group, Multicenter Study To Evaluate The Antiviral Activity Of Multiple Doses Of A Small Molecule Direct Antiviral Agent In Chronically Infected Hepatitis C Subjects.

Phase 1 study in HVC (Hepatitis C Virus) infected subjects to determine pharmacokinetics, safety and efficacy in subjects with no or inadequate response to prior treatment.

Study Overview

• Status: Completed
• Conditions: Hepatitis, Chronic; Hepatitis C Virus
• Intervention / Treatment: Drug: Small Molecule Agent (PF-868554); Drug: Small Molecule Agent (PF-868554)

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32608
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

HCV Positive With HCV RNA>100,000 iu/ml Genotype 1; COHORT A- non responders or partial

Exclusion Criteria:

HIV HBV co-infection Decompensated liver disease Liver disease due to causes other than HCV, AFP>200ng/ml

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort B	Drug: Small Molecule Agent (PF-868554); Study drug will be administered 700mg BID in the fed state for three days.; Drug: Small Molecule Agent (PF-868554); Study drug will be given 450mg BID for a duration of 10 days.
Experimental: Cohort A; Dose study drug in subjects who have previously failed to respond to interferon based therapies	Drug: Small Molecule Agent (PF-868554); Study drug will be administered 700mg BID in the fed state for three days.; Drug: Small Molecule Agent (PF-868554); Study drug will be given 450mg BID for a duration of 10 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 11 (Cohort A): Full Analysis Set	Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (lower limit of quantification [LLOQ] = 12 international unit per milliliter [IU/mL]). Baseline value calculated as an average of screening, Day 0 and Day 1 (0 hour) measurements. Change from baseline in plasma log10 HCV RNA was calculated for all participants after the last day of dosing (Day 11 for Cohort A).	Baseline, Day 11
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 11 (Cohort A): Modified Analysis Set	Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Baseline value calculated as an average of screening, Day 0 and Day 1 (0 hour) measurements. Change from baseline in plasma log10 HCV RNA was calculated for all participants after the last day of dosing (Day 11 for Cohort A).	Baseline, Day 11
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 4 (Cohort B): Full Analysis Set	Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Baseline value calculated as an average of screening, Day 0 and Day 1 (0 hour) measurements. Change from baseline in plasma log10 HCV RNA was calculated for all participants after the last day of dosing (Day 4 for Cohort B).	Baseline, Day 4
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 4 (Cohort B): Modified Analysis Set	Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Baseline value calculated as the average of screening, Day 0 and Day 1 (0 hour) measurements. Change from baseline in plasma log10 HCV RNA was calculated for all participants after the last day of dosing (Day 4 for Cohort B).	Baseline, Day 4
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Nadir: Full Analysis Set	Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Change from baseline in plasma Log10 HCV RNA at nadir signified the maximum change observed during the study.	Baseline, Nadir (lowest HCV RNA level), assessed up to Day 11 for Cohort A and Day 4 for Cohort B
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Nadir: Modified Analysis Set	Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Change from baseline in plasma Log10 HCV RNA at nadir signified the maximum change observed during the study.	Baseline, Nadir (lowest HCV RNA level), assessed up to Day 11 for Cohort A and Day 4 for Cohort B

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)	Area under the concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 12 hours. AUCtau was evaluated at first dose on Day 1 for Cohort A and B, and at last dose for Cohort A (Day 10) and Cohort B (Day 3).	Predose, 0.5, 1, 2, 6, 8, 12 hours (hrs) postdose on Day 1 for Cohort A and B, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12 hrs post-evening dose on Day 3 for Cohort B, predose, 0.5, 1, 2, 4, 8, 12 hrs postdose on Day 10 for Cohort A
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	Area under the serum concentration time-curve from zero to the last measured concentration (AUClast). AUClast was evaluated at first dose on Day 1 for Cohort A and B, and at last dose for Cohort A (Day 10) and Cohort B (Day 3).	Predose, 0.5, 1, 2, 6, 8, 12, 14 hrs postdose on Day 1 for Cohort A, B, pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort A
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]	AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). AUC (0 - ∞) was evaluated at last dose for Cohort A (Day 10) and Cohort B (Day 3).	Pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort A
Plasma Concentration at The End of Dosing Interval (Ctau)	Ctau was evaluated at first dose on Day 1 for Cohort A and B, and at last dose for Cohort A (Day 10) and Cohort B (Day 3).	Predose, 0.5, 1, 2, 6, 8, 12 hours (hrs) postdose on Day 1 for Cohort A and B, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12 hrs post-evening dose on Day 3 for Cohort B, predose, 0.5, 1, 2, 4, 8, 12 hrs postdose on Day 10 for Cohort A
Maximum Observed Plasma Concentration (Cmax)	Cmax was evaluated at first dose on Day 1 for Cohort A and B, and at last dose for Cohort A (Day 10) and Cohort B (Day 3).	Predose, 0.5, 1, 2, 6, 8, 12, 14 hrs postdose on Day 1 for Cohort A, B, pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort A
Time to Reach Maximum Observed Plasma Concentration (Tmax)	Tmax was evaluated at first dose on Day 1 for Cohort A and B, and at last dose for Cohort A (Day 10) and Cohort B (Day 3).	Predose, 0.5, 1, 2, 6, 8, 12, 14 hrs postdose on Day 1 for Cohort A, B, pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort A
Plasma Decay Half-Life (t1/2)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Half-life was evaluated at last dose for Cohort A (Day 10) and Cohort B (Day 3).	Pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort A

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Wagner F, Thompson R, Kantaridis C, Simpson P, Troke PJ, Jagannatha S, Neelakantan S, Purohit VS, Hammond JL. Antiviral activity of the hepatitis C virus polymerase inhibitor filibuvir in genotype 1-infected patients. Hepatology. 2011 Jul;54(1):50-9. doi: 10.1002/hep.24342.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: April 25, 2008
• First Submitted That Met QC Criteria: April 29, 2008
• First Posted (Estimate): May 5, 2008

Study Record Updates

• Last Update Posted (Estimate): January 14, 2014
• Last Update Submitted That Met QC Criteria: November 25, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic
• Other Study ID Numbers: A8121006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No