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

NCT00445315 | Completed Phase 1 Results

• 1 other identifier: A8121002
• Study Type: interventional
• Target: 32
• Locations: 3 countries
• Sites: 4

Brief Summary

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

Conditions

Hepatitis C

Outcome Measures

Primary Outcomes (19)

• 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 Outcomes (2)

• Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at Day 8

  Baseline, Day 8

• Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Variants Resistant to PF-00868554

  Screening up to Day 8

Study Arms (5)

2

EXPERIMENTAL

Drug: PF-00868554

3

EXPERIMENTAL

Drug: PF-00868554

1

EXPERIMENTAL

Drug: PF-00868554

4

EXPERIMENTAL

Drug: PF-00868554

5

PLACEBO COMPARATOR

Drug: Placebo

Interventions

PF-00868554 DRUG

300 mg BID

1

Placebo DRUG

Placebo

5

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Current or prior treatment with IFN and/or RBV
• Evidence of decompensated liver disease

Sponsors & Collaborators

• Pfizer: lead

Study Sites (4)

Pfizer Investigational Site

Brussels, 1070, Belgium

Location

Pfizer Investigational Site

Berlin, 10117, Germany

Location

Pfizer Investigational Site

Berlin, 12351, Germany

Location

Pfizer Investigational Site

Dundee, DD1 9SY, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 21488067 DERIVED

Related Links

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

MeSH Terms

Conditions

Hepatitis C

Interventions

filibuvir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Limitations and Caveats

Designation of outcomes as primary, secondary based on team's input. Results for relationship analyses of baseline susceptibility to PF-00868554 and/or non-structural 5B genotype and change in HCV RNA was not done, as per change in planned analysis.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2007
• First Posted: March 8, 2007
• Study Start: January 1, 2007
• Primary Completion: June 1, 2008
• Study Completion: June 1, 2008
• Last Updated: February 17, 2014
• Results First Posted: February 17, 2014

Record last verified: 2014-01

Locations

BE (1); DE (2); GB (1)