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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00445315

Enrollment

Registered

2007-03-08

Start date

2007-01-31

Completion date

2008-06-30

Last updated

2014-02-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hepatitis C

Brief summary

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

Interventions

DRUGPF-00868554

300 mg BID

DRUGPlacebo

Placebo

Study design

Allocation

RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

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

Design outcomes

Primary

Measure	Time frame	Description
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 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).
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).
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	—
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).
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.
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.
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).
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).
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.
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.
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.
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

Measure	Time frame	Description
Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Variants Resistant to PF-00868554	Screening up to Day 8	—
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.

Countries

Belgium, Germany, United Kingdom

Participant flow

Participants by arm

Arm	Count
PF-00868554 100 mg Twice Daily PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.	6
PF-00868554 300 mg Twice Daily PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.	6
PF-00868554 300 mg Three Times Daily PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.	6
PF-00868554 450 mg Twice Daily PF-00868554 450 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.	6
Placebo Placebo matched to PF-00868554 powder for oral solution, twice daily or three times daily on Day 1 through Day 7 and once in morning on Day 8.	8
Total	32

Baseline characteristics

Characteristic	PF-00868554 100 mg Twice Daily	PF-00868554 300 mg Twice Daily	PF-00868554 300 mg Three Times Daily	PF-00868554 450 mg Twice Daily	Placebo	Total
Age, Customized 18 to 44 years	3 participants	2 participants	2 participants	4 participants	6 participants	17 participants
Age, Customized 45 to 64 years	3 participants	4 participants	3 participants	2 participants	2 participants	14 participants
Age, Customized greater than or equal to 65 years	0 participants	0 participants	1 participants	0 participants	0 participants	1 participants
Sex: Female, Male Female	0 Participants	1 Participants	2 Participants	1 Participants	1 Participants	5 Participants
Sex: Female, Male Male	6 Participants	5 Participants	4 Participants	5 Participants	7 Participants	27 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	5 / 6	5 / 6	3 / 6	5 / 6	8 / 8
serious Total, serious adverse events	0 / 6	0 / 6	0 / 6	0 / 6	0 / 8

Outcome results

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.

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

Population: PP analysis set included all participants who received PF-00868554 and had sufficient plasma concentration data to enable calculation of the PK parameters.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-00868554 100 mg Twice Daily	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Day 1	13816.6 ng*hour/mL	Standard Deviation 6698.11
PF-00868554 300 mg Twice Daily	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Day 1	73653.0 ng*hour/mL	Standard Deviation 19681.78
PF-00868554 300 mg Three Times Daily	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Day 1	52933.7 ng*hour/mL	Standard Deviation 30925.32
PF-00868554 450 mg Twice Daily	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Day 1	110158.1 ng*hour/mL	Standard Deviation 44416.51

Primary

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

Population: PP analysis set included all participants who received PF-00868554 and had sufficient plasma concentration data to enable calculation of the PK parameters.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-00868554 100 mg Twice Daily	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Day 8	20632.5 ng*hour/mL	Standard Deviation 13934.95
PF-00868554 300 mg Twice Daily	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Day 8	84983.3 ng*hour/mL	Standard Deviation 20225.45
PF-00868554 300 mg Three Times Daily	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Day 8	59492.4 ng*hour/mL	Standard Deviation 26992.82
PF-00868554 450 mg Twice Daily	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Day 8	120849.4 ng*hour/mL	Standard Deviation 42396.74

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.

Time frame: 0 to 12 hours, 12 to 24 hours post-dose

Population: PP analysis set included all participants who received PF-00868554 and had sufficient plasma concentration data to enable calculation of the PK parameters. Urine collection interval was 12 hours and not 8 hours; therefore, urinary PK parameters were not calculated for three times daily regimens.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-00868554 100 mg Twice Daily	Cumulative Amount of Drug Recovered Unchanged in Urine (Ae): Day 1	13490943.6 nanogram	Standard Deviation 5465341.72
PF-00868554 300 mg Twice Daily	Cumulative Amount of Drug Recovered Unchanged in Urine (Ae): Day 1	47306427.2 nanogram	Standard Deviation 10029440.68
PF-00868554 300 mg Three Times Daily	Cumulative Amount of Drug Recovered Unchanged in Urine (Ae): Day 1	58500433.1 nanogram	Standard Deviation 23166241.78

Primary

Cumulative Amount of Drug Recovered Unchanged in Urine (Ae): Day 8

Time frame: 0 to 12 hours, 12 to 24 hours post-dose

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-00868554 100 mg Twice Daily	Cumulative Amount of Drug Recovered Unchanged in Urine (Ae): Day 8	23157156.8 nanogram	Standard Deviation 8370778.62
PF-00868554 300 mg Twice Daily	Cumulative Amount of Drug Recovered Unchanged in Urine (Ae): Day 8	61249508.4 nanogram	Standard Deviation 13917200.98
PF-00868554 300 mg Three Times Daily	Cumulative Amount of Drug Recovered Unchanged in Urine (Ae): Day 8	59663120.9 nanogram	Standard Deviation 17455075.93

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).

Time frame: -24 to 0 hours (pre-dose) on Day 1 (Day 0); 0 to 24 hours post-dose on Day 8

Population: PP analysis set included all participants who received PF-00868554 and had sufficient plasma concentration data to enable calculation of the PK parameters.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-00868554 100 mg Twice Daily	Day 8 to Day 1 Ratio of the 6 Beta-Hydroxyl Cortisol to Cortisol Ratios	1.29 ratio	Standard Deviation 0.38
PF-00868554 300 mg Twice Daily	Day 8 to Day 1 Ratio of the 6 Beta-Hydroxyl Cortisol to Cortisol Ratios	0.99 ratio	Standard Deviation 0.24
PF-00868554 300 mg Three Times Daily	Day 8 to Day 1 Ratio of the 6 Beta-Hydroxyl Cortisol to Cortisol Ratios	1.13 ratio	Standard Deviation 0.09
PF-00868554 450 mg Twice Daily	Day 8 to Day 1 Ratio of the 6 Beta-Hydroxyl Cortisol to Cortisol Ratios	1.06 ratio	Standard Deviation 0.27
Placebo	Day 8 to Day 1 Ratio of the 6 Beta-Hydroxyl Cortisol to Cortisol Ratios	1.20 ratio	Standard Deviation 0.62

Primary

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

Population: Per Protocol (PP) analysis set included all participants who received PF-00868554 and had sufficient plasma concentration data to enable calculation of the pharmacokinetics (PK) parameters.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-00868554 100 mg Twice Daily	Maximum Observed Plasma Concentration (Cmax): Day 1	3467.0 nanogram per milliliter (ng/mL)	Standard Deviation 1085.36
PF-00868554 300 mg Twice Daily	Maximum Observed Plasma Concentration (Cmax): Day 1	27437.1 nanogram per milliliter (ng/mL)	Standard Deviation 7875.45
PF-00868554 300 mg Three Times Daily	Maximum Observed Plasma Concentration (Cmax): Day 1	23046.7 nanogram per milliliter (ng/mL)	Standard Deviation 10526.66
PF-00868554 450 mg Twice Daily	Maximum Observed Plasma Concentration (Cmax): Day 1	48392.6 nanogram per milliliter (ng/mL)	Standard Deviation 13466.65

Primary

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

Population: PP analysis set included all participants who received PF-00868554 and had sufficient plasma concentration data to enable calculation of the PK parameters.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-00868554 100 mg Twice Daily	Maximum Observed Plasma Concentration (Cmax): Day 8	5858.8 nanogram per milliliter (ng/mL)	Standard Deviation 2312.65
PF-00868554 300 mg Twice Daily	Maximum Observed Plasma Concentration (Cmax): Day 8	33111.4 nanogram per milliliter (ng/mL)	Standard Deviation 8680.94
PF-00868554 300 mg Three Times Daily	Maximum Observed Plasma Concentration (Cmax): Day 8	30919.1 nanogram per milliliter (ng/mL)	Standard Deviation 6576.52
PF-00868554 450 mg Twice Daily	Maximum Observed Plasma Concentration (Cmax): Day 8	57724.5 nanogram per milliliter (ng/mL)	Standard Deviation 17739.87

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).

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

Population: PP analysis set included all participants who received PF-00868554 and had sufficient plasma concentration data to enable calculation of the PK parameters.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-00868554 100 mg Twice Daily	Minimum Observed Plasma Trough Concentration (Cmin): Day 8	448.6 ng/mL	Standard Deviation 422.18
PF-00868554 300 mg Twice Daily	Minimum Observed Plasma Trough Concentration (Cmin): Day 8	904.8 ng/mL	Standard Deviation 342.73
PF-00868554 300 mg Three Times Daily	Minimum Observed Plasma Trough Concentration (Cmin): Day 8	1055.9 ng/mL	Standard Deviation 437.59
PF-00868554 450 mg Twice Daily	Minimum Observed Plasma Trough Concentration (Cmin): Day 8	706.0 ng/mL	Standard Deviation 661.12

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).

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

Population: PP analysis set included all participants who received PF-00868554 and had sufficient plasma concentration data to enable calculation of the PK parameters.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-00868554 100 mg Twice Daily	Observed Accumulation Ratio for Cmax (Rac Cmax)	1.68 ratio	Standard Deviation 0.46
PF-00868554 300 mg Twice Daily	Observed Accumulation Ratio for Cmax (Rac Cmax)	1.20 ratio	Standard Deviation 0.25
PF-00868554 300 mg Three Times Daily	Observed Accumulation Ratio for Cmax (Rac Cmax)	1.34 ratio	Standard Deviation 0.28
PF-00868554 450 mg Twice Daily	Observed Accumulation Ratio for Cmax (Rac Cmax)	1.19 ratio	Standard Deviation 0.46

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).

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

Population: PP analysis set included all participants who received PF-00868554 and had sufficient plasma concentration data to enable calculation of the PK parameters.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-00868554 100 mg Twice Daily	Observed Accumulation Ratio (Rac)	1.49 ratio	Standard Deviation 0.25
PF-00868554 300 mg Twice Daily	Observed Accumulation Ratio (Rac)	1.15 ratio	Standard Deviation 0.24
PF-00868554 300 mg Three Times Daily	Observed Accumulation Ratio (Rac)	1.12 ratio	Standard Deviation 0.15
PF-00868554 450 mg Twice Daily	Observed Accumulation Ratio (Rac)	1.09 ratio	Standard Deviation 0.19

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.

Time frame: 0 to 12 hours, 12 to 24 hours post-dose

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-00868554 100 mg Twice Daily	Percent of Dose Recovered Unchanged in Urine (Ae%): Day 1	13.49 percent dose recovered	Standard Deviation 5.46
PF-00868554 300 mg Twice Daily	Percent of Dose Recovered Unchanged in Urine (Ae%): Day 1	15.77 percent dose recovered	Standard Deviation 3.34
PF-00868554 300 mg Three Times Daily	Percent of Dose Recovered Unchanged in Urine (Ae%): Day 1	13.00 percent dose recovered	Standard Deviation 5.15

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.

Time frame: 0 to 12 hours, 12 to 24 hours post-dose

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-00868554 100 mg Twice Daily	Percent of Dose Recovered Unchanged in Urine (Ae%): Day 8	23.16 percent dose recovered	Standard Deviation 8.37
PF-00868554 300 mg Twice Daily	Percent of Dose Recovered Unchanged in Urine (Ae%): Day 8	20.42 percent dose recovered	Standard Deviation 4.64
PF-00868554 300 mg Three Times Daily	Percent of Dose Recovered Unchanged in Urine (Ae%): Day 8	13.26 percent dose recovered	Standard Deviation 3.88

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).

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

Population: PP analysis set included all participants who received PF-00868554 and had sufficient plasma concentration data to enable calculation of the PK parameters. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm	Measure	Value (MEAN)	Dispersion
PF-00868554 100 mg Twice Daily	Plasma Decay Half-Life (t1/2): Day 8	12.58 hour	Standard Deviation 3.01
PF-00868554 300 mg Twice Daily	Plasma Decay Half-Life (t1/2): Day 8	10.77 hour	Standard Deviation 4.29
PF-00868554 300 mg Three Times Daily	Plasma Decay Half-Life (t1/2): Day 8	9.17 hour	Standard Deviation 0.62
PF-00868554 450 mg Twice Daily	Plasma Decay Half-Life (t1/2): Day 8	8.13 hour	Standard Deviation 0.72

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).

Time frame: -24 to 0 hours (pre-dose) on Day 1 (Day 0)

Population: PP analysis set included all participants who received PF-00868554 and had sufficient plasma concentration data to enable calculation of the PK parameters.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-00868554 100 mg Twice Daily	Ratio of 6 Beta-Hydroxyl Cortisol to Cortisol: Day 1	2.93 ratio	Standard Deviation 1.55
PF-00868554 300 mg Twice Daily	Ratio of 6 Beta-Hydroxyl Cortisol to Cortisol: Day 1	3.94 ratio	Standard Deviation 1.42
PF-00868554 300 mg Three Times Daily	Ratio of 6 Beta-Hydroxyl Cortisol to Cortisol: Day 1	4.65 ratio	Standard Deviation 2.95
PF-00868554 450 mg Twice Daily	Ratio of 6 Beta-Hydroxyl Cortisol to Cortisol: Day 1	4.32 ratio	Standard Deviation 1.62
Placebo	Ratio of 6 Beta-Hydroxyl Cortisol to Cortisol: Day 1	3.56 ratio	Standard Deviation 1.68

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).

Time frame: 0 to 24 hours post-dose on Day 8

Population: PP analysis set included all participants who received PF-00868554 and had sufficient plasma concentration data to enable calculation of the PK parameters.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-00868554 100 mg Twice Daily	Ratio of 6 Beta-Hydroxyl Cortisol to Cortisol: Day 8	3.79 ratio	Standard Deviation 1.47
PF-00868554 300 mg Twice Daily	Ratio of 6 Beta-Hydroxyl Cortisol to Cortisol: Day 8	3.90 ratio	Standard Deviation 1.56
PF-00868554 300 mg Three Times Daily	Ratio of 6 Beta-Hydroxyl Cortisol to Cortisol: Day 8	5.26 ratio	Standard Deviation 2.79
PF-00868554 450 mg Twice Daily	Ratio of 6 Beta-Hydroxyl Cortisol to Cortisol: Day 8	4.58 ratio	Standard Deviation 0.97
Placebo	Ratio of 6 Beta-Hydroxyl Cortisol to Cortisol: Day 8	4.30 ratio	Standard Deviation 1.05

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.

Time frame: 0 to 12 hours, 12 to 24 hours post-dose

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-00868554 100 mg Twice Daily	Renal Clearance (CLr): Day 1	16.27 mL/minute	Standard Deviation 6.5
PF-00868554 300 mg Twice Daily	Renal Clearance (CLr): Day 1	10.70 mL/minute	Standard Deviation 2.19
PF-00868554 300 mg Three Times Daily	Renal Clearance (CLr): Day 1	8.85 mL/minute	Standard Deviation 5.9

Primary

Renal Clearance (CLr): Day 8

Time frame: 0 to 12 hours, 12 to 24 hours post-dose

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-00868554 100 mg Twice Daily	Renal Clearance (CLr): Day 8	18.70 mL/minute	Standard Deviation 3.79
PF-00868554 300 mg Twice Daily	Renal Clearance (CLr): Day 8	12.01 mL/minute	Standard Deviation 3.5
PF-00868554 300 mg Three Times Daily	Renal Clearance (CLr): Day 8	8.23 mL/minute	Standard Deviation 4.26

Primary

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

Population: PP analysis set included all participants who received PF-00868554 and had sufficient plasma concentration data to enable calculation of the PK parameters.

Arm	Measure	Value (MEDIAN)
PF-00868554 100 mg Twice Daily	Time to Reach Maximum Observed Plasma Concentration (Tmax): Day 1	1.00 hour
PF-00868554 300 mg Twice Daily	Time to Reach Maximum Observed Plasma Concentration (Tmax): Day 1	0.50 hour
PF-00868554 300 mg Three Times Daily	Time to Reach Maximum Observed Plasma Concentration (Tmax): Day 1	0.51 hour
PF-00868554 450 mg Twice Daily	Time to Reach Maximum Observed Plasma Concentration (Tmax): Day 1	0.50 hour

Primary

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

Population: PP analysis set included all participants who received PF-00868554 and had sufficient plasma concentration data to enable calculation of the PK parameters.

Arm	Measure	Value (MEDIAN)
PF-00868554 100 mg Twice Daily	Time to Reach Maximum Observed Plasma Concentration (Tmax): Day 8	0.76 hour
PF-00868554 300 mg Twice Daily	Time to Reach Maximum Observed Plasma Concentration (Tmax): Day 8	0.50 hour
PF-00868554 300 mg Three Times Daily	Time to Reach Maximum Observed Plasma Concentration (Tmax): Day 8	0.50 hour
PF-00868554 450 mg Twice Daily	Time to Reach Maximum Observed Plasma Concentration (Tmax): Day 8	0.50 hour

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.

Time frame: Baseline, Day 8

Population: Full analysis set (FAS) included all randomized participants who received at least 1 dose of study medication.

Arm	Measure	Group	Value (MEAN)	Dispersion
PF-00868554 100 mg Twice Daily	Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at Day 8	Baseline	6.14 log10 copies/mL	Standard Deviation 0.39
PF-00868554 100 mg Twice Daily	Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at Day 8	Change at Day 8	-0.68 log10 copies/mL	Standard Deviation 0.38
PF-00868554 300 mg Twice Daily	Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at Day 8	Baseline	6.05 log10 copies/mL	Standard Deviation 0.35
PF-00868554 300 mg Twice Daily	Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at Day 8	Change at Day 8	-1.26 log10 copies/mL	Standard Deviation 0.58
PF-00868554 300 mg Three Times Daily	Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at Day 8	Baseline	6.02 log10 copies/mL	Standard Deviation 0.5
PF-00868554 300 mg Three Times Daily	Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at Day 8	Change at Day 8	-1.95 log10 copies/mL	Standard Deviation 0.51
PF-00868554 450 mg Twice Daily	Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at Day 8	Change at Day 8	-1.21 log10 copies/mL	Standard Deviation 0.7
PF-00868554 450 mg Twice Daily	Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at Day 8	Baseline	5.75 log10 copies/mL	Standard Deviation 0.65
Placebo	Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at Day 8	Baseline	6.02 log10 copies/mL	Standard Deviation 0.58
Placebo	Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at Day 8	Change at Day 8	-0.08 log10 copies/mL	Standard Deviation 0.1

Secondary

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

Time frame: Screening up to Day 8

Population: FAS included all randomized participants who received at least 1 dose of study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm	Measure	Value (NUMBER)
PF-00868554 100 mg Twice Daily	Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Variants Resistant to PF-00868554	0 participants
PF-00868554 300 mg Twice Daily	Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Variants Resistant to PF-00868554	6 participants
PF-00868554 300 mg Three Times Daily	Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Variants Resistant to PF-00868554	2 participants
PF-00868554 450 mg Twice Daily	Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Variants Resistant to PF-00868554	3 participants
Placebo	Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Variants Resistant to PF-00868554	0 participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

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

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Baseline characteristics

Adverse events

Outcome results

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

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

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

Cumulative Amount of Drug Recovered Unchanged in Urine (Ae): Day 8

Day 8 to Day 1 Ratio of the 6 Beta-Hydroxyl Cortisol to Cortisol Ratios

Maximum Observed Plasma Concentration (Cmax): Day 1

Maximum Observed Plasma Concentration (Cmax): Day 8

Minimum Observed Plasma Trough Concentration (Cmin): Day 8

Observed Accumulation Ratio for Cmax (Rac Cmax)

Observed Accumulation Ratio (Rac)

Percent of Dose Recovered Unchanged in Urine (Ae%): Day 1

Percent of Dose Recovered Unchanged in Urine (Ae%): Day 8

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

Ratio of 6 Beta-Hydroxyl Cortisol to Cortisol: Day 1

Ratio of 6 Beta-Hydroxyl Cortisol to Cortisol: Day 8

Renal Clearance (CLr): Day 1

Renal Clearance (CLr): Day 8

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

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

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

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