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

Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00445315
• Other study ID #: A8121002
• Status: Completed
• Phase: Phase 1
• First received: March 6, 2007
• Last updated: January 2, 2014
• Start date: January 2007
• Est. completion date: June 2008

Study information

• Verified date: January 2014
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: June 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C

Intervention

Drug:
• PF-00868554
300 mg BID
• PF-00868554
450 mg BID
• PF-00868554
100 mg BID
• PF-00868554
300 mg TID
• Placebo
Placebo

Locations

Country	Name	City	State
Belgium	Pfizer Investigational Site	Bruxelles
Germany	Pfizer Investigational Site	Berlin
Germany	Pfizer Investigational Site	Berlin
United Kingdom	Pfizer Investigational Site	Dundee

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

Belgium,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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)	No
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Variants Resistant to PF-00868554		Screening up to Day 8	No

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