A Phase 1 Study Of PF-00868554 In Hepatitis C Virus (HCV) Positive Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00445315
First received: March 6, 2007
Last updated: January 2, 2014
Last verified: January 2014
  Purpose

Assess the safety, tolerability and pharmacokinetics of multiple oral doses of PF-00868554 in HCV positive patient volunteers


Condition Intervention Phase
Hepatitis C
Drug: PF-00868554
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1, Randomized, Double Blind (3rd Party Open), Placebo-controlled, Sequential Group, Multicentre Study To Evaluate The Multiple Dose Safety, Tolerability, Pharmacokinetics And Pharmacodynamics, of PF-00868554 in Hepatitis C Virus (HCV) Positive Otherwise Healthy Patient Volunteers

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Maximum Observed Plasma Concentration (Cmax): Day 1 [ Time Frame: 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 hours post-dose for twice daily dose; 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 hours post-dose for three times daily dose ] [ Designated as safety issue: No ]
  • Maximum Observed Plasma Concentration (Cmax): Day 8 [ Time Frame: 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post-dose ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax): Day 1 [ Time Frame: 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 hours post-dose for twice daily dose; 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 hours post-dose for three times daily dose ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax): Day 8 [ Time Frame: 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post-dose ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Day 1 [ Time Frame: 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 hours post-dose for twice daily dose; 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 hours post-dose for three times daily dose ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from time zero to end of dosing interval (tau), where dosing interval is 8 hours for three times daily regimens and 12 hours for the twice daily regimens.

  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Day 8 [ Time Frame: 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post-dose ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from time zero to end of dosing interval (tau), where dosing interval is 8 hours for three times daily regimens and 12 hours for the twice daily regimens.

  • Minimum Observed Plasma Trough Concentration (Cmin): Day 8 [ Time Frame: 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post-dose on Day 8 ] [ Designated as safety issue: No ]
    The Cmin of PF-04691502 was assessed following repeated oral dose administration for 8 days (multiple dose PK).

  • Plasma Decay Half-Life (t1/2): Day 8 [ Time Frame: 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post-dose on Day 8 ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. The t1/2 of PF-04691502 was assessed following repeated oral dose administration for 8 days (multiple dose PK).

  • Observed Accumulation Ratio (Rac) [ Time Frame: 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 hours post-dose on Day 1; 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post-dose on Day 8 ] [ Designated as safety issue: No ]
    Rac was calculated as, area under the curve from time zero to end of dosing interval on Day 8 (AUCtau) divided by area under the curve from time zero to end of dosing interval on Day 1(AUCtau).

  • Observed Accumulation Ratio for Cmax (Rac Cmax) [ Time Frame: 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 hours post-dose on Day 1; 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post-dose on Day 8 ] [ Designated as safety issue: No ]
    Rac Cmax was calculated as, maximum observed plasma concentration on Day 8 (Cmax) divided by maximum observed plasma concentration on Day 1(Cmax).

  • Cumulative Amount of Drug Recovered Unchanged in Urine (Ae): Day 1 [ Time Frame: 0 to 12 hours, 12 to 24 hours post-dose ] [ Designated as safety issue: No ]
    Ae is the cumulative amount of drug recovered unchanged in urine during the dosing interval, where the dosing interval is 12 hours. Cumulative amount was calculated as sum of urine drug concentration in sample volume for each collection interval. Sample volume = (urine weight in gram [g]/1.020), where 1.020 g/mL is the approximate specific gravity of urine.

  • Cumulative Amount of Drug Recovered Unchanged in Urine (Ae): Day 8 [ Time Frame: 0 to 12 hours, 12 to 24 hours post-dose ] [ Designated as safety issue: No ]
    Ae is the cumulative amount of drug recovered unchanged in urine during the dosing interval, where the dosing interval is 12 hours. Cumulative amount was calculated as sum of urine drug concentration in sample volume for each collection interval. Sample volume = (urine weight in gram [g]/1.020), where 1.020 g/mL is the approximate specific gravity of urine.

  • Percent of Dose Recovered Unchanged in Urine (Ae%): Day 1 [ Time Frame: 0 to 12 hours, 12 to 24 hours post-dose ] [ Designated as safety issue: No ]
    Percent of dose recovered unchanged in urine during the dosing interval=100*(cumulative amount of drug recovered unchanged in urine [Ae] divided by dose), where the dosing interval is 12 hours.

  • Percent of Dose Recovered Unchanged in Urine (Ae%): Day 8 [ Time Frame: 0 to 12 hours, 12 to 24 hours post-dose ] [ Designated as safety issue: No ]
    Percent of dose recovered unchanged in urine during the dosing interval=100 (cumulative amount of drug recovered unchanged in urine [Ae] divided by dose), where the dosing interval is 12 hours.

  • Renal Clearance (CLr): Day 1 [ Time Frame: 0 to 12 hours, 12 to 24 hours post-dose ] [ Designated as safety issue: No ]
    Renal clearance was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau), where dosing interval is 12 hours.

  • Renal Clearance (CLr): Day 8 [ Time Frame: 0 to 12 hours, 12 to 24 hours post-dose ] [ Designated as safety issue: No ]
    Renal clearance was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau), where dosing interval is 12 hours.

  • Ratio of 6 Beta-Hydroxyl Cortisol to Cortisol: Day 1 [ Time Frame: -24 to 0 hours (pre-dose) on Day 1 (Day 0) ] [ Designated as safety issue: No ]
    Urine 6 beta-hydroxyl cortisol and cortisol concentrations were measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).

  • Ratio of 6 Beta-Hydroxyl Cortisol to Cortisol: Day 8 [ Time Frame: 0 to 24 hours post-dose on Day 8 ] [ Designated as safety issue: No ]
    Urine 6 beta-hydroxyl cortisol and cortisol concentrations were measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).

  • Day 8 to Day 1 Ratio of the 6 Beta-Hydroxyl Cortisol to Cortisol Ratios [ Time Frame: -24 to 0 hours (pre-dose) on Day 1 (Day 0); 0 to 24 hours post-dose on Day 8 ] [ Designated as safety issue: No ]
    Urine 6 beta-hydroxyl cortisol and cortisol concentrations were measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).


Secondary Outcome Measures:
  • Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at Day 8 [ Time Frame: Baseline, Day 8 ] [ Designated as safety issue: No ]
    HCV RNA levels were determined using the Abbott RealTime HCV polymerase chain reaction (PCR) assay (lower limit of detection [LOD] = 12 international unit per milliliter [IU/mL]). Baseline value calculated as the average of the screening Day 0 and Day 1 pre-dose measurements. The plasma HCV RNA data was log10 transformed, and the change in log10 HCV RNA at Day 8 post-dose from baseline was calculated.

  • Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Variants Resistant to PF-00868554 [ Time Frame: Screening up to Day 8 ] [ Designated as safety issue: No ]

Enrollment: 32
Study Start Date: January 2007
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 2 Drug: PF-00868554
450 mg BID
Experimental: 3 Drug: PF-00868554
100 mg BID
Experimental: 1 Drug: PF-00868554
300 mg BID
Experimental: 4 Drug: PF-00868554
300 mg TID
Placebo Comparator: 5 Drug: Placebo
Placebo

  Eligibility

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

Inclusion Criteria:

  • HCV RNA ≥ 100,000 IU/mL at screening
  • Genotype 1a or 1b

Exclusion Criteria:

  • Current or prior treatment with IFN and/or RBV
  • Evidence of decompensated liver disease
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00445315

Locations
Belgium
Pfizer Investigational Site
Bruxelles, Belgium, 1070
Germany
Pfizer Investigational Site
Berlin, Germany, 10117
Pfizer Investigational Site
Berlin, Germany, 12351
United Kingdom
Pfizer Investigational Site
Dundee, United Kingdom, DD1 9SY
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: NCT00445315     History of Changes
Other Study ID Numbers: A8121002
Study First Received: March 6, 2007
Results First Received: December 9, 2013
Last Updated: January 2, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections

ClinicalTrials.gov processed this record on September 22, 2014