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

Phase 1
Completed
Conditions
Hepatitis C
Interventions
Drug: PF-00868554
Drug: Placebo
Registration Number
NCT00445315
Lead Sponsor
Pfizer
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
32
Inclusion Criteria
  • HCV RNA ≥ 100,000 IU/mL at screening
  • Genotype 1a or 1b
Read More
Exclusion Criteria
  • Current or prior treatment with IFN and/or RBV
  • Evidence of decompensated liver disease
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
2PF-00868554-
3PF-00868554-
1PF-00868554-
4PF-00868554-
5Placebo-
Primary Outcome Measures
NameTimeMethod
Time to Reach Maximum Observed Plasma Concentration (Tmax): Day 80 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post-dose
Maximum Observed Plasma Concentration (Cmax): Day 10 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
Maximum Observed Plasma Concentration (Cmax): Day 80 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post-dose
Plasma Decay Half-Life (t1/2): Day 80 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post-dose on Day 8

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).

Cumulative Amount of Drug Recovered Unchanged in Urine (Ae): Day 10 to 12 hours, 12 to 24 hours post-dose

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.

Day 8 to Day 1 Ratio of the 6 Beta-Hydroxyl Cortisol to Cortisol Ratios-24 to 0 hours (pre-dose) on Day 1 (Day 0); 0 to 24 hours post-dose on Day 8

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 80 to 24 hours post-dose on Day 8

Urine 6 beta-hydroxyl cortisol and cortisol concentrations were measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).

Time to Reach Maximum Observed Plasma Concentration (Tmax): Day 10 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
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Day 80 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post-dose

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 80 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post-dose on Day 8

The Cmin of PF-04691502 was assessed following repeated oral dose administration for 8 days (multiple dose PK).

Observed Accumulation Ratio (Rac)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

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)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

Rac Cmax was calculated as, maximum observed plasma concentration on Day 8 (Cmax) divided by maximum observed plasma concentration on Day 1(Cmax).

Percent of Dose Recovered Unchanged in Urine (Ae%): Day 10 to 12 hours, 12 to 24 hours post-dose

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 80 to 12 hours, 12 to 24 hours post-dose

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.

Ratio of 6 Beta-Hydroxyl Cortisol to Cortisol: Day 1-24 to 0 hours (pre-dose) on Day 1 (Day 0)

Urine 6 beta-hydroxyl cortisol and cortisol concentrations were measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Day 10 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

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.

Cumulative Amount of Drug Recovered Unchanged in Urine (Ae): Day 80 to 12 hours, 12 to 24 hours post-dose

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.

Renal Clearance (CLr): Day 10 to 12 hours, 12 to 24 hours post-dose

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 80 to 12 hours, 12 to 24 hours post-dose

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.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at Day 8Baseline, Day 8

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-00868554Screening up to Day 8

Trial Locations

Locations (1)

Pfizer Investigational Site

🇬🇧

Dundee, United Kingdom

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