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

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

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

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Placebo; Drug: PF-00868554; Drug: PF-00868554; Drug: PF-00868554; Drug: PF-00868554

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1070
    • Pfizer Investigational Site
• Germany
  • Berlin, Germany, 10117
    • Pfizer Investigational Site
  • Berlin, Germany, 12351
    • Pfizer Investigational Site
• United Kingdom
  • Dundee, United Kingdom, DD1 9SY
    • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: PF-00868554; 300 mg BID; Drug: PF-00868554; 450 mg BID; Drug: PF-00868554; 100 mg BID; Drug: PF-00868554; 300 mg TID
Experimental: 2	Drug: PF-00868554; 300 mg BID; Drug: PF-00868554; 450 mg BID; Drug: PF-00868554; 100 mg BID; Drug: PF-00868554; 300 mg TID
Experimental: 3	Drug: PF-00868554; 300 mg BID; Drug: PF-00868554; 450 mg BID; Drug: PF-00868554; 100 mg BID; Drug: PF-00868554; 300 mg TID
Experimental: 4	Drug: PF-00868554; 300 mg BID; Drug: PF-00868554; 450 mg BID; Drug: PF-00868554; 100 mg BID; Drug: PF-00868554; 300 mg TID
Placebo Comparator: 5	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Day 1	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.	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	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.	0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post-dose
Minimum Observed Plasma Trough Concentration (Cmin): Day 8	The Cmin of PF-04691502 was assessed following repeated oral dose administration for 8 days (multiple dose PK).	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 (t1/2): 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).	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
Observed Accumulation Ratio (Rac)	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).	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
Observed Accumulation Ratio for Cmax (Rac Cmax)	Rac Cmax was calculated as, maximum observed plasma concentration on Day 8 (Cmax) divided by maximum observed plasma concentration on Day 1(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
Cumulative Amount of Drug Recovered Unchanged in Urine (Ae): Day 1	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.	0 to 12 hours, 12 to 24 hours post-dose
Cumulative Amount of Drug Recovered Unchanged in Urine (Ae): Day 8	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.	0 to 12 hours, 12 to 24 hours post-dose
Percent of Dose Recovered Unchanged in Urine (Ae%): Day 1	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.	0 to 12 hours, 12 to 24 hours post-dose
Percent of Dose Recovered Unchanged in Urine (Ae%): Day 8	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.	0 to 12 hours, 12 to 24 hours post-dose
Renal Clearance (CLr): Day 1	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.	0 to 12 hours, 12 to 24 hours post-dose
Renal Clearance (CLr): Day 8	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.	0 to 12 hours, 12 to 24 hours post-dose
Ratio of 6 Beta-Hydroxyl Cortisol to Cortisol: Day 1	Urine 6 beta-hydroxyl cortisol and cortisol concentrations were measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).	-24 to 0 hours (pre-dose) on Day 1 (Day 0)
Ratio of 6 Beta-Hydroxyl Cortisol to Cortisol: Day 8	Urine 6 beta-hydroxyl cortisol and cortisol concentrations were measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).	0 to 24 hours post-dose on Day 8
Day 8 to Day 1 Ratio of the 6 Beta-Hydroxyl Cortisol to Cortisol Ratios	Urine 6 beta-hydroxyl cortisol and cortisol concentrations were measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).	-24 to 0 hours (pre-dose) on Day 1 (Day 0); 0 to 24 hours post-dose on Day 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 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.	Baseline, Day 8
Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Variants Resistant to PF-00868554		Screening up to Day 8

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Wagner F, Thompson R, Kantaridis C, Simpson P, Troke PJ, Jagannatha S, Neelakantan S, Purohit VS, Hammond JL. Antiviral activity of the hepatitis C virus polymerase inhibitor filibuvir in genotype 1-infected patients. Hepatology. 2011 Jul;54(1):50-9. doi: 10.1002/hep.24342.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: March 6, 2007
• First Submitted That Met QC Criteria: March 7, 2007
• First Posted (Estimate): March 8, 2007

Study Record Updates

• Last Update Posted (Estimate): February 17, 2014
• Last Update Submitted That Met QC Criteria: January 2, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C
• Other Study ID Numbers: A8121002