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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00671671
First received: April 25, 2008
Last updated: November 25, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Hepatitis, Chronic
Hepatitis C Virus
Drug: Small Molecule Agent (PF-868554)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 11 (Cohort A): Full Analysis Set [ Time Frame: Baseline, Day 11 ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 11 (Cohort A): Modified Analysis Set [ Time Frame: Baseline, Day 11 ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 4 (Cohort B): Full Analysis Set [ Time Frame: Baseline, Day 4 ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 4 (Cohort B): Modified Analysis Set [ Time Frame: Baseline, Day 4 ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Nadir: Full Analysis Set [ Time Frame: Baseline, Nadir (lowest HCV RNA level), assessed up to Day 11 for Cohort A and Day 4 for Cohort B ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Nadir: Modified Analysis Set [ Time Frame: Baseline, Nadir (lowest HCV RNA level), assessed up to Day 11 for Cohort A and Day 4 for Cohort B ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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).

  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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).

  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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).

  • Plasma Concentration at The End of Dosing Interval (Ctau) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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).

  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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).

  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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).

  • Plasma Decay Half-Life (t1/2) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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).


Enrollment: 20
Study Start Date: April 2008
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort B Drug: Small Molecule Agent (PF-868554)
Study drug will be administered 700mg BID in the fed state for three 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 given 450mg BID for a duration of 10 days.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00671671

Locations
United States, Florida
Pfizer Investigational Site
Gainesville, Florida, United States, 32608
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00671671     History of Changes
Other Study ID Numbers: A8121006
Study First Received: April 25, 2008
Results First Received: November 25, 2013
Last Updated: November 25, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014