Trial Outcomes & Findings for A Phase 1 Study Of PF-00868554 In Hepatitis C Virus (HCV) Positive Patients (NCT NCT00445315)

NCT ID: NCT00445315

Last Updated: 2014-02-17

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

32 participants

Primary outcome timeframe

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

Results posted on

2014-02-17

Participant Flow

Participant milestones

Participant milestones
Measure
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.
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.
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.
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.
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.
Overall Study
STARTED
6
6
6
6
8
Overall Study
COMPLETED
6
6
6
6
8
Overall Study
NOT COMPLETED
0
0
0
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
PF-00868554 100 mg Twice Daily
n=6 Participants
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 450 mg Twice Daily
n=6 Participants
PF-00868554 450 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
Placebo
n=8 Participants
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.
Total
n=32 Participants
Total of all reporting groups
Age, Customized
18 to 44 years
3 participants
n=5 Participants
2 participants
n=7 Participants
2 participants
n=5 Participants
4 participants
n=4 Participants
6 participants
n=21 Participants
17 participants
n=8 Participants
Age, Customized
45 to 64 years
3 participants
n=5 Participants
4 participants
n=7 Participants
3 participants
n=5 Participants
2 participants
n=4 Participants
2 participants
n=21 Participants
14 participants
n=8 Participants
Age, Customized
greater than or equal to 65 years
0 participants
n=5 Participants
0 participants
n=7 Participants
1 participants
n=5 Participants
0 participants
n=4 Participants
0 participants
n=21 Participants
1 participants
n=8 Participants
Sex: Female, Male
Female
0 Participants
n=5 Participants
1 Participants
n=7 Participants
2 Participants
n=5 Participants
1 Participants
n=4 Participants
1 Participants
n=21 Participants
5 Participants
n=8 Participants
Sex: Female, Male
Male
6 Participants
n=5 Participants
5 Participants
n=7 Participants
4 Participants
n=5 Participants
5 Participants
n=4 Participants
7 Participants
n=21 Participants
27 Participants
n=8 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
PF-00868554 100 mg Twice Daily
n=6 Participants
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 450 mg Twice Daily
n=6 Participants
PF-00868554 450 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
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.
Maximum Observed Plasma Concentration (Cmax): Day 1
3467.0 nanogram per milliliter (ng/mL)
Standard Deviation 1085.36
27437.1 nanogram per milliliter (ng/mL)
Standard Deviation 7875.45
23046.7 nanogram per milliliter (ng/mL)
Standard Deviation 10526.66
48392.6 nanogram per milliliter (ng/mL)
Standard Deviation 13466.65

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
PF-00868554 100 mg Twice Daily
n=6 Participants
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 450 mg Twice Daily
n=6 Participants
PF-00868554 450 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
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.
Maximum Observed Plasma Concentration (Cmax): Day 8
5858.8 nanogram per milliliter (ng/mL)
Standard Deviation 2312.65
33111.4 nanogram per milliliter (ng/mL)
Standard Deviation 8680.94
30919.1 nanogram per milliliter (ng/mL)
Standard Deviation 6576.52
57724.5 nanogram per milliliter (ng/mL)
Standard Deviation 17739.87

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
PF-00868554 100 mg Twice Daily
n=6 Participants
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 450 mg Twice Daily
n=6 Participants
PF-00868554 450 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
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.
Time to Reach Maximum Observed Plasma Concentration (Tmax): Day 1
1.00 hour
Interval 0.5 to 1.5
0.50 hour
Interval 0.5 to 1.0
0.51 hour
Interval 0.5 to 1.0
0.50 hour
Interval 0.5 to 1.03

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
PF-00868554 100 mg Twice Daily
n=6 Participants
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 450 mg Twice Daily
n=6 Participants
PF-00868554 450 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
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.
Time to Reach Maximum Observed Plasma Concentration (Tmax): Day 8
0.76 hour
Interval 0.5 to 1.0
0.50 hour
Interval 0.5 to 1.0
0.50 hour
Interval 0.48 to 0.5
0.50 hour
Interval 0.48 to 0.52

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
PF-00868554 100 mg Twice Daily
n=6 Participants
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 450 mg Twice Daily
n=6 Participants
PF-00868554 450 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
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.
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Day 1
13816.6 ng*hour/mL
Standard Deviation 6698.11
73653.0 ng*hour/mL
Standard Deviation 19681.78
52933.7 ng*hour/mL
Standard Deviation 30925.32
110158.1 ng*hour/mL
Standard Deviation 44416.51

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
PF-00868554 100 mg Twice Daily
n=6 Participants
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 450 mg Twice Daily
n=6 Participants
PF-00868554 450 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
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.
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Day 8
20632.5 ng*hour/mL
Standard Deviation 13934.95
84983.3 ng*hour/mL
Standard Deviation 20225.45
59492.4 ng*hour/mL
Standard Deviation 26992.82
120849.4 ng*hour/mL
Standard Deviation 42396.74

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure
PF-00868554 100 mg Twice Daily
n=6 Participants
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 450 mg Twice Daily
n=6 Participants
PF-00868554 450 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
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.
Minimum Observed Plasma Trough Concentration (Cmin): Day 8
448.6 ng/mL
Standard Deviation 422.18
904.8 ng/mL
Standard Deviation 342.73
1055.9 ng/mL
Standard Deviation 437.59
706.0 ng/mL
Standard Deviation 661.12

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
PF-00868554 100 mg Twice Daily
n=6 Participants
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=5 Participants
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 450 mg Twice Daily
n=6 Participants
PF-00868554 450 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
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.
Plasma Decay Half-Life (t1/2): Day 8
12.58 hour
Standard Deviation 3.01
10.77 hour
Standard Deviation 4.29
9.17 hour
Standard Deviation 0.62
8.13 hour
Standard Deviation 0.72

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
PF-00868554 100 mg Twice Daily
n=6 Participants
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 450 mg Twice Daily
n=6 Participants
PF-00868554 450 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
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.
Observed Accumulation Ratio (Rac)
1.49 ratio
Standard Deviation 0.25
1.15 ratio
Standard Deviation 0.24
1.12 ratio
Standard Deviation 0.15
1.09 ratio
Standard Deviation 0.19

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure
PF-00868554 100 mg Twice Daily
n=6 Participants
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 450 mg Twice Daily
n=6 Participants
PF-00868554 450 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
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.
Observed Accumulation Ratio for Cmax (Rac Cmax)
1.68 ratio
Standard Deviation 0.46
1.20 ratio
Standard Deviation 0.25
1.34 ratio
Standard Deviation 0.28
1.19 ratio
Standard Deviation 0.46

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
PF-00868554 100 mg Twice Daily
n=6 Participants
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
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.
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.
Cumulative Amount of Drug Recovered Unchanged in Urine (Ae): Day 1
13490943.6 nanogram
Standard Deviation 5465341.72
47306427.2 nanogram
Standard Deviation 10029440.68
58500433.1 nanogram
Standard Deviation 23166241.78

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
PF-00868554 100 mg Twice Daily
n=6 Participants
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
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.
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.
Cumulative Amount of Drug Recovered Unchanged in Urine (Ae): Day 8
23157156.8 nanogram
Standard Deviation 8370778.62
61249508.4 nanogram
Standard Deviation 13917200.98
59663120.9 nanogram
Standard Deviation 17455075.93

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
PF-00868554 100 mg Twice Daily
n=6 Participants
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
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.
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.
Percent of Dose Recovered Unchanged in Urine (Ae%): Day 1
13.49 percent dose recovered
Standard Deviation 5.46
15.77 percent dose recovered
Standard Deviation 3.34
13.00 percent dose recovered
Standard Deviation 5.15

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
PF-00868554 100 mg Twice Daily
n=6 Participants
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
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.
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.
Percent of Dose Recovered Unchanged in Urine (Ae%): Day 8
23.16 percent dose recovered
Standard Deviation 8.37
20.42 percent dose recovered
Standard Deviation 4.64
13.26 percent dose recovered
Standard Deviation 3.88

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
PF-00868554 100 mg Twice Daily
n=6 Participants
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
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.
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.
Renal Clearance (CLr): Day 1
16.27 mL/minute
Standard Deviation 6.50
10.70 mL/minute
Standard Deviation 2.19
8.85 mL/minute
Standard Deviation 5.90

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
PF-00868554 100 mg Twice Daily
n=6 Participants
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
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.
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.
Renal Clearance (CLr): Day 8
18.70 mL/minute
Standard Deviation 3.79
12.01 mL/minute
Standard Deviation 3.50
8.23 mL/minute
Standard Deviation 4.26

PRIMARY outcome

Timeframe: -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.

Urine 6 beta-hydroxyl cortisol and cortisol concentrations were measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).

Outcome measures

Outcome measures
Measure
PF-00868554 100 mg Twice Daily
n=6 Participants
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 450 mg Twice Daily
n=6 Participants
PF-00868554 450 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
Placebo
n=8 Participants
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.
Ratio of 6 Beta-Hydroxyl Cortisol to Cortisol: Day 1
2.93 ratio
Standard Deviation 1.55
3.94 ratio
Standard Deviation 1.42
4.65 ratio
Standard Deviation 2.95
4.32 ratio
Standard Deviation 1.62
3.56 ratio
Standard Deviation 1.68

PRIMARY outcome

Timeframe: 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.

Urine 6 beta-hydroxyl cortisol and cortisol concentrations were measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).

Outcome measures

Outcome measures
Measure
PF-00868554 100 mg Twice Daily
n=6 Participants
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 450 mg Twice Daily
n=6 Participants
PF-00868554 450 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
Placebo
n=8 Participants
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.
Ratio of 6 Beta-Hydroxyl Cortisol to Cortisol: Day 8
3.79 ratio
Standard Deviation 1.47
3.90 ratio
Standard Deviation 1.56
5.26 ratio
Standard Deviation 2.79
4.58 ratio
Standard Deviation 0.97
4.30 ratio
Standard Deviation 1.05

PRIMARY outcome

Timeframe: -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.

Urine 6 beta-hydroxyl cortisol and cortisol concentrations were measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).

Outcome measures

Outcome measures
Measure
PF-00868554 100 mg Twice Daily
n=6 Participants
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 450 mg Twice Daily
n=6 Participants
PF-00868554 450 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
Placebo
n=8 Participants
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.
Day 8 to Day 1 Ratio of the 6 Beta-Hydroxyl Cortisol to Cortisol Ratios
1.29 ratio
Standard Deviation 0.38
0.99 ratio
Standard Deviation 0.24
1.13 ratio
Standard Deviation 0.09
1.06 ratio
Standard Deviation 0.27
1.20 ratio
Standard Deviation 0.62

SECONDARY outcome

Timeframe: Baseline, Day 8

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

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.

Outcome measures

Outcome measures
Measure
PF-00868554 100 mg Twice Daily
n=6 Participants
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 450 mg Twice Daily
n=6 Participants
PF-00868554 450 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
Placebo
n=8 Participants
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.
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
6.05 log10 copies/mL
Standard Deviation 0.35
6.02 log10 copies/mL
Standard Deviation 0.50
5.75 log10 copies/mL
Standard Deviation 0.65
6.02 log10 copies/mL
Standard Deviation 0.58
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
-1.26 log10 copies/mL
Standard Deviation 0.58
-1.95 log10 copies/mL
Standard Deviation 0.51
-1.21 log10 copies/mL
Standard Deviation 0.70
-0.08 log10 copies/mL
Standard Deviation 0.10

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
PF-00868554 100 mg Twice Daily
n=6 Participants
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 Participants
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 450 mg Twice Daily
n=6 Participants
PF-00868554 450 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
Placebo
n=7 Participants
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.
Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Variants Resistant to PF-00868554
0 participants
6 participants
2 participants
3 participants
0 participants

Adverse Events

PF-00868554 100 mg Twice Daily

Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths

PF-00868554 300 mg Twice Daily

Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths

PF-00868554 300 mg Three Times Daily

Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths

PF-00868554 450 mg Twice Daily

Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
PF-00868554 100 mg Twice Daily
n=6 participants at risk
PF-00868554 100 milligram (mg) powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Twice Daily
n=6 participants at risk
PF-00868554 300 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 300 mg Three Times Daily
n=6 participants at risk
PF-00868554 300 mg powder for oral solution, three times daily on Day 1 through Day 7 and once in morning on Day 8.
PF-00868554 450 mg Twice Daily
n=6 participants at risk
PF-00868554 450 mg powder for oral solution, twice daily on Day 1 through Day 7 and once in morning on Day 8.
Placebo
n=8 participants at risk
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.
Eye disorders
Eye irritation
0.00%
0/6
0.00%
0/6
0.00%
0/6
0.00%
0/6
12.5%
1/8
Eye disorders
Foreign body sensation in eyes
16.7%
1/6
0.00%
0/6
0.00%
0/6
0.00%
0/6
0.00%
0/8
Eye disorders
Ocular hyperaemia
0.00%
0/6
16.7%
1/6
0.00%
0/6
0.00%
0/6
12.5%
1/8
Eye disorders
Photophobia
0.00%
0/6
0.00%
0/6
0.00%
0/6
0.00%
0/6
12.5%
1/8
Gastrointestinal disorders
Abdominal pain upper
0.00%
0/6
0.00%
0/6
16.7%
1/6
16.7%
1/6
0.00%
0/8
Gastrointestinal disorders
Change of bowel habit
0.00%
0/6
16.7%
1/6
0.00%
0/6
0.00%
0/6
12.5%
1/8
Gastrointestinal disorders
Diarrhoea
0.00%
0/6
16.7%
1/6
0.00%
0/6
0.00%
0/6
0.00%
0/8
Gastrointestinal disorders
Dyspepsia
16.7%
1/6
0.00%
0/6
0.00%
0/6
0.00%
0/6
0.00%
0/8
Gastrointestinal disorders
Flatulence
66.7%
4/6
16.7%
1/6
0.00%
0/6
0.00%
0/6
12.5%
1/8
Gastrointestinal disorders
Nausea
0.00%
0/6
16.7%
1/6
16.7%
1/6
0.00%
0/6
0.00%
0/8
Gastrointestinal disorders
Vomiting
16.7%
1/6
0.00%
0/6
16.7%
1/6
0.00%
0/6
0.00%
0/8
General disorders
Application site erythema
0.00%
0/6
0.00%
0/6
0.00%
0/6
0.00%
0/6
12.5%
1/8
General disorders
Asthenia
0.00%
0/6
16.7%
1/6
0.00%
0/6
0.00%
0/6
0.00%
0/8
General disorders
Chills
0.00%
0/6
16.7%
1/6
0.00%
0/6
0.00%
0/6
0.00%
0/8
General disorders
Fatigue
16.7%
1/6
0.00%
0/6
0.00%
0/6
16.7%
1/6
25.0%
2/8
Hepatobiliary disorders
Liver tenderness
0.00%
0/6
0.00%
0/6
0.00%
0/6
0.00%
0/6
12.5%
1/8
Infections and infestations
Abscess limb
0.00%
0/6
16.7%
1/6
0.00%
0/6
0.00%
0/6
0.00%
0/8
Infections and infestations
Gastroenteritis
0.00%
0/6
0.00%
0/6
0.00%
0/6
16.7%
1/6
0.00%
0/8
Infections and infestations
Nasopharyngitis
16.7%
1/6
16.7%
1/6
0.00%
0/6
0.00%
0/6
0.00%
0/8
Infections and infestations
Rash pustular
0.00%
0/6
0.00%
0/6
0.00%
0/6
16.7%
1/6
0.00%
0/8
Infections and infestations
Rhinitis
0.00%
0/6
0.00%
0/6
0.00%
0/6
16.7%
1/6
12.5%
1/8
Injury, poisoning and procedural complications
Excoriation
0.00%
0/6
0.00%
0/6
0.00%
0/6
0.00%
0/6
12.5%
1/8
Musculoskeletal and connective tissue disorders
Back pain
0.00%
0/6
0.00%
0/6
0.00%
0/6
16.7%
1/6
0.00%
0/8
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
0.00%
0/6
0.00%
0/6
0.00%
0/6
16.7%
1/6
0.00%
0/8
Nervous system disorders
Disturbance in attention
0.00%
0/6
0.00%
0/6
0.00%
0/6
16.7%
1/6
0.00%
0/8
Nervous system disorders
Dizziness
0.00%
0/6
0.00%
0/6
0.00%
0/6
16.7%
1/6
0.00%
0/8
Nervous system disorders
Headache
16.7%
1/6
33.3%
2/6
0.00%
0/6
33.3%
2/6
37.5%
3/8
Nervous system disorders
Intercostal neuralgia
0.00%
0/6
16.7%
1/6
0.00%
0/6
0.00%
0/6
0.00%
0/8
Nervous system disorders
Paraesthesia
0.00%
0/6
0.00%
0/6
16.7%
1/6
0.00%
0/6
0.00%
0/8
Nervous system disorders
Sinus headache
16.7%
1/6
16.7%
1/6
0.00%
0/6
0.00%
0/6
0.00%
0/8
Psychiatric disorders
Libido decreased
16.7%
1/6
0.00%
0/6
0.00%
0/6
0.00%
0/6
12.5%
1/8
Psychiatric disorders
Nervousness
0.00%
0/6
16.7%
1/6
0.00%
0/6
0.00%
0/6
0.00%
0/8
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
16.7%
1/6
0.00%
0/6
0.00%
0/6
0.00%
0/6
0.00%
0/8
Skin and subcutaneous tissue disorders
Dermatitis contact
0.00%
0/6
0.00%
0/6
16.7%
1/6
0.00%
0/6
0.00%
0/8
Skin and subcutaneous tissue disorders
Dry skin
0.00%
0/6
16.7%
1/6
0.00%
0/6
0.00%
0/6
0.00%
0/8
Skin and subcutaneous tissue disorders
Hyperhidrosis
0.00%
0/6
16.7%
1/6
0.00%
0/6
0.00%
0/6
0.00%
0/8
Skin and subcutaneous tissue disorders
Pruritus
16.7%
1/6
0.00%
0/6
0.00%
0/6
0.00%
0/6
0.00%
0/8
Skin and subcutaneous tissue disorders
Urticaria
0.00%
0/6
0.00%
0/6
0.00%
0/6
0.00%
0/6
12.5%
1/8

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Results disclosure agreements

  • Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
  • Publication restrictions are in place

Restriction type: OTHER