A Phase 1 Study Of PF-00868554 In Hepatitis C Virus (HCV) Positive Patients
- Conditions
- Hepatitis C
- Interventions
- Drug: PF-00868554Drug: 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
- HCV RNA ≥ 100,000 IU/mL at screening
- Genotype 1a or 1b
- Current or prior treatment with IFN and/or RBV
- Evidence of decompensated liver disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 2 PF-00868554 - 3 PF-00868554 - 1 PF-00868554 - 4 PF-00868554 - 5 Placebo -
- Primary Outcome Measures
Name Time Method Time to Reach Maximum Observed Plasma Concentration (Tmax): Day 8 0 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 1 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 Maximum Observed Plasma Concentration (Cmax): Day 8 0 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 8 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 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 1 0 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 8 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).
Time to Reach Maximum Observed Plasma Concentration (Tmax): Day 1 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 Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Day 8 0 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 8 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 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 1 0 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 8 0 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 1 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 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 8 0 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 1 0 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 8 0 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
Name Time Method Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at Day 8 Baseline, 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-00868554 Screening up to Day 8
Trial Locations
- Locations (1)
Pfizer Investigational Site
🇬🇧Dundee, United Kingdom