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

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

PF-00868554

Placebo

About this trial

This is an interventional treatment trial for Hepatitis C

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Pfizer Investigational Site
Pfizer Investigational Site
Pfizer Investigational Site
Pfizer Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Placebo Comparator

Arm Label

2

3

1

4

5

Arm Description

Outcomes

Primary Outcome Measures

Maximum Observed Plasma Concentration (Cmax): Day 1

Maximum Observed Plasma Concentration (Cmax): Day 8

Time to Reach Maximum Observed Plasma Concentration (Tmax): Day 1

Time to Reach Maximum Observed Plasma Concentration (Tmax): Day 8

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.

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.

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).

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).

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).

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).

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.

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.

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.

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.

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.

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.

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).

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).

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).

Secondary Outcome Measures

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.

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

Full Information

NCT ID

NCT00445315

First Posted

March 6, 2007

Last Updated

January 2, 2014

Sponsor

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT00445315

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2014

Overall Recruitment Status

Completed

Study Start Date

January 2007 (undefined)

Primary Completion Date

June 2008 (Actual)

Study Completion Date

June 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis C

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

32 (Actual)

8. Arms, Groups, and Interventions

Arm Title

2

Arm Type

Experimental

Arm Title

3

Arm Type

Experimental

Arm Title

1

Arm Type

Experimental

Arm Title

4

Arm Type

Experimental

Arm Title

5

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

PF-00868554

Intervention Description

300 mg BID

Intervention Type

Drug

Intervention Name(s)

PF-00868554

Intervention Description

450 mg BID

Intervention Type

Drug

Intervention Name(s)

PF-00868554

Intervention Description

100 mg BID

Intervention Type

Drug

Intervention Name(s)

PF-00868554

Intervention Description

300 mg TID

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo

Primary Outcome Measure Information:

Title

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

Title

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

Title

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

Title

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

Title

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Day 1

Description

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.

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

Title

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Day 8

Description

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.

Time Frame

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

Title

Minimum Observed Plasma Trough Concentration (Cmin): Day 8

Description

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

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

Title

Plasma Decay Half-Life (t1/2): Day 8

Description

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).

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

Title

Observed Accumulation Ratio (Rac)

Description

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).

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

Title

Observed Accumulation Ratio for Cmax (Rac Cmax)

Description

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

Title

Cumulative Amount of Drug Recovered Unchanged in Urine (Ae): Day 1

Description

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.

Time Frame