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

Hepatitis C Virus Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00671671
• Other study ID #: A8121006
• Status: Completed
• Phase: Phase 1
• First received: April 25, 2008
• Last updated: November 25, 2013
• Start date: April 2008
• Est. completion date: December 2008

Study information

• Verified date: November 2013
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C Virus
• Hepatitis, Chronic

Intervention

Drug:
• Small Molecule Agent (PF-868554)
Study drug will be administered 700mg BID in the fed state for three days.
• Small Molecule Agent (PF-868554)
Study drug will be given 450mg BID for a duration of 10 days.

Locations

Country	Name	City	State
United States	Pfizer Investigational Site	Gainesville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)]	AUC (0 - 8) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8). AUC (0 - 8) 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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

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