Trial Outcomes & Findings for Phase 1 Study To Evaluate Antiviral Activity Of Small Molecule Direct Antiviral Agent At Multiple Doses In Subjects With Chronically Infected Hepatitis C Virus. (NCT NCT00671671)
NCT ID: NCT00671671
Last Updated: 2014-01-14
Results Overview
Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (lower limit of quantification \[LLOQ\] = 12 international unit per milliliter \[IU/mL\]). Baseline value calculated as an average of screening, Day 0 and Day 1 (0 hour) measurements. Change from baseline in plasma log10 HCV RNA was calculated for all participants after the last day of dosing (Day 11 for Cohort A).
COMPLETED
PHASE1
20 participants
Baseline, Day 11
2014-01-14
Participant Flow
Participant milestones
| Measure |
PF-00868554 450 mg (Cohort A)
Participants who had a history of unsuccessful treatment for hepatitis C virus (HCV) with an interferon-alpha (IFN-alpha) regimen (with or without ribavirin \[RBV\]) due to lack of response or relapse, received PF-00868554 450 milligram (mg) tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 10 morning dose in a fasted state.
|
PF-00868554 700 mg (Cohort B)
Participants who did not receive any prior treatment for HCV with an IFN-alpha regimen (with or without RBV) or who discontinued from an IFN-alpha regimen (with or without RBV) after less than or equal to (\<=) 2 weeks of treatment due to tolerability issues or other reasons, received PF-00868554 700 mg tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 3 evening dose in a fed state.
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
10
|
|
Overall Study
COMPLETED
|
10
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase 1 Study To Evaluate Antiviral Activity Of Small Molecule Direct Antiviral Agent At Multiple Doses In Subjects With Chronically Infected Hepatitis C Virus.
Baseline characteristics by cohort
| Measure |
PF-00868554 450 mg (Cohort A)
n=10 Participants
Participants who had a history of unsuccessful treatment for hepatitis C virus (HCV) with an interferon-alpha (IFN-alpha) regimen (with or without ribavirin \[RBV\]) due to lack of response or relapse, received PF-00868554 450 milligram (mg) tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 10 morning dose in a fasted state.
|
PF-00868554 700 mg (Cohort B)
n=10 Participants
Participants who did not receive any prior treatment for HCV with an IFN-alpha regimen (with or without RBV) or who discontinued from an IFN-alpha regimen (with or without RBV) after less than or equal to (\<=) 2 weeks of treatment due to tolerability issues or other reasons, received PF-00868554 700 mg tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 3 evening dose in a fed state.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
18 to 44 years
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Age, Customized
45 to 64 years
|
9 participants
n=5 Participants
|
7 participants
n=7 Participants
|
16 participants
n=5 Participants
|
|
Age, Customized
greater than or equal to (>=) 65 years
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Day 11Population: Full Analysis Set (FAS) included all randomized participants who took at least 1 dose of study medication and had both baseline and at least 1 valid post-baseline endpoint measurements for HCV viral load.
Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (lower limit of quantification \[LLOQ\] = 12 international unit per milliliter \[IU/mL\]). Baseline value calculated as an average of screening, Day 0 and Day 1 (0 hour) measurements. Change from baseline in plasma log10 HCV RNA was calculated for all participants after the last day of dosing (Day 11 for Cohort A).
Outcome measures
| Measure |
PF-00868554 450 mg (Cohort A)
n=10 Participants
Participants who had a history of unsuccessful treatment for hepatitis C virus (HCV) with an interferon-alpha (IFN-alpha) regimen (with or without ribavirin \[RBV\]) due to lack of response or relapse, received PF-00868554 450 milligram (mg) tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 10 morning dose in a fasted state.
|
PF-00868554 700 mg (Cohort B)
Participants who did not receive any prior treatment for HCV with an IFN-alpha regimen (with or without RBV) or who discontinued from an IFN-alpha regimen (with or without RBV) after less than or equal to (\<=) 2 weeks of treatment due to tolerability issues or other reasons, received PF-00868554 700 mg tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 3 evening dose in a fed state.
|
|---|---|---|
|
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 11 (Cohort A): Full Analysis Set
Baseline
|
6.11 log10 IU/mL
Standard Deviation 0.449
|
—
|
|
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 11 (Cohort A): Full Analysis Set
Change at Day 11
|
-0.45 log10 IU/mL
Standard Deviation 0.439
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 11Population: Modified Analysis Set (MAS): a subset of FAS which included all participants who had received complete dosage in the corresponding treatment regimen.
Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Baseline value calculated as an average of screening, Day 0 and Day 1 (0 hour) measurements. Change from baseline in plasma log10 HCV RNA was calculated for all participants after the last day of dosing (Day 11 for Cohort A).
Outcome measures
| Measure |
PF-00868554 450 mg (Cohort A)
n=10 Participants
Participants who had a history of unsuccessful treatment for hepatitis C virus (HCV) with an interferon-alpha (IFN-alpha) regimen (with or without ribavirin \[RBV\]) due to lack of response or relapse, received PF-00868554 450 milligram (mg) tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 10 morning dose in a fasted state.
|
PF-00868554 700 mg (Cohort B)
Participants who did not receive any prior treatment for HCV with an IFN-alpha regimen (with or without RBV) or who discontinued from an IFN-alpha regimen (with or without RBV) after less than or equal to (\<=) 2 weeks of treatment due to tolerability issues or other reasons, received PF-00868554 700 mg tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 3 evening dose in a fed state.
|
|---|---|---|
|
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 11 (Cohort A): Modified Analysis Set
Baseline
|
6.11 log10 IU/mL
Standard Deviation 0.449
|
—
|
|
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 11 (Cohort A): Modified Analysis Set
Change at Day 11
|
-0.45 log10 IU/mL
Standard Deviation 0.439
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 4Population: FAS included all randomized participants who took at least 1 dose of study medication and had both baseline and at least 1 valid post-baseline endpoint measurements for HCV viral load.
Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Baseline value calculated as an average of screening, Day 0 and Day 1 (0 hour) measurements. Change from baseline in plasma log10 HCV RNA was calculated for all participants after the last day of dosing (Day 4 for Cohort B).
Outcome measures
| Measure |
PF-00868554 450 mg (Cohort A)
n=10 Participants
Participants who had a history of unsuccessful treatment for hepatitis C virus (HCV) with an interferon-alpha (IFN-alpha) regimen (with or without ribavirin \[RBV\]) due to lack of response or relapse, received PF-00868554 450 milligram (mg) tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 10 morning dose in a fasted state.
|
PF-00868554 700 mg (Cohort B)
Participants who did not receive any prior treatment for HCV with an IFN-alpha regimen (with or without RBV) or who discontinued from an IFN-alpha regimen (with or without RBV) after less than or equal to (\<=) 2 weeks of treatment due to tolerability issues or other reasons, received PF-00868554 700 mg tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 3 evening dose in a fed state.
|
|---|---|---|
|
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 4 (Cohort B): Full Analysis Set
Change at Day 4
|
-2.15 log10 IU/mL
Standard Deviation 0.252
|
—
|
|
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 4 (Cohort B): Full Analysis Set
Baseline
|
6.39 log10 IU/mL
Standard Deviation 0.455
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 4Population: MAS: a subset of FAS which included all participants who had received complete dosage in the corresponding treatment regimen.
Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Baseline value calculated as the average of screening, Day 0 and Day 1 (0 hour) measurements. Change from baseline in plasma log10 HCV RNA was calculated for all participants after the last day of dosing (Day 4 for Cohort B).
Outcome measures
| Measure |
PF-00868554 450 mg (Cohort A)
n=10 Participants
Participants who had a history of unsuccessful treatment for hepatitis C virus (HCV) with an interferon-alpha (IFN-alpha) regimen (with or without ribavirin \[RBV\]) due to lack of response or relapse, received PF-00868554 450 milligram (mg) tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 10 morning dose in a fasted state.
|
PF-00868554 700 mg (Cohort B)
Participants who did not receive any prior treatment for HCV with an IFN-alpha regimen (with or without RBV) or who discontinued from an IFN-alpha regimen (with or without RBV) after less than or equal to (\<=) 2 weeks of treatment due to tolerability issues or other reasons, received PF-00868554 700 mg tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 3 evening dose in a fed state.
|
|---|---|---|
|
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 4 (Cohort B): Modified Analysis Set
Baseline
|
6.39 log10 IU/mL
Standard Deviation 0.455
|
—
|
|
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 4 (Cohort B): Modified Analysis Set
Change at Day 4
|
-2.15 log10 IU/mL
Standard Deviation 0.252
|
—
|
PRIMARY outcome
Timeframe: Baseline, Nadir (lowest HCV RNA level), assessed up to Day 11 for Cohort A and Day 4 for Cohort BPopulation: FAS included all randomized participants who took at least 1 dose of study medication and had both baseline and at least 1 valid post-baseline endpoint measurements for HCV viral load.
Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Change from baseline in plasma Log10 HCV RNA at nadir signified the maximum change observed during the study.
Outcome measures
| Measure |
PF-00868554 450 mg (Cohort A)
n=10 Participants
Participants who had a history of unsuccessful treatment for hepatitis C virus (HCV) with an interferon-alpha (IFN-alpha) regimen (with or without ribavirin \[RBV\]) due to lack of response or relapse, received PF-00868554 450 milligram (mg) tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 10 morning dose in a fasted state.
|
PF-00868554 700 mg (Cohort B)
n=10 Participants
Participants who did not receive any prior treatment for HCV with an IFN-alpha regimen (with or without RBV) or who discontinued from an IFN-alpha regimen (with or without RBV) after less than or equal to (\<=) 2 weeks of treatment due to tolerability issues or other reasons, received PF-00868554 700 mg tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 3 evening dose in a fed state.
|
|---|---|---|
|
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Nadir: Full Analysis Set
|
-2.2 log10 IU/mL
Standard Deviation 0.23
|
-2.3 log10 IU/mL
Standard Deviation 0.34
|
PRIMARY outcome
Timeframe: Baseline, Nadir (lowest HCV RNA level), assessed up to Day 11 for Cohort A and Day 4 for Cohort BPopulation: MAS: a subset of FAS which included all participants who had received complete dosage in the corresponding treatment regimen.
Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Change from baseline in plasma Log10 HCV RNA at nadir signified the maximum change observed during the study.
Outcome measures
| Measure |
PF-00868554 450 mg (Cohort A)
n=10 Participants
Participants who had a history of unsuccessful treatment for hepatitis C virus (HCV) with an interferon-alpha (IFN-alpha) regimen (with or without ribavirin \[RBV\]) due to lack of response or relapse, received PF-00868554 450 milligram (mg) tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 10 morning dose in a fasted state.
|
PF-00868554 700 mg (Cohort B)
n=10 Participants
Participants who did not receive any prior treatment for HCV with an IFN-alpha regimen (with or without RBV) or who discontinued from an IFN-alpha regimen (with or without RBV) after less than or equal to (\<=) 2 weeks of treatment due to tolerability issues or other reasons, received PF-00868554 700 mg tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 3 evening dose in a fed state.
|
|---|---|---|
|
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Nadir: Modified Analysis Set
|
-2.2 log10 IU/mL
Standard Deviation 0.23
|
-2.3 log10 IU/mL
Standard Deviation 0.34
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 2, 6, 8, 12 hours (hrs) postdose on Day 1 for Cohort A and B, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12 hrs post-evening dose on Day 3 for Cohort B, predose, 0.5, 1, 2, 4, 8, 12 hrs postdose on Day 10 for Cohort APopulation: Per Protocol (PP) analysis set included all participants who took PF-00866554 and had sufficient plasma concentration data to facilitate calculation of the pharmacokinetic (PK) parameters. Here 'n' signifies those participants who were evaluable for this measure at specified time points for each arm, respectively.
Area under the concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 12 hours. AUCtau was evaluated at first dose on Day 1 for Cohort A and B, and at last dose for Cohort A (Day 10) and Cohort B (Day 3).
Outcome measures
| Measure |
PF-00868554 450 mg (Cohort A)
n=10 Participants
Participants who had a history of unsuccessful treatment for hepatitis C virus (HCV) with an interferon-alpha (IFN-alpha) regimen (with or without ribavirin \[RBV\]) due to lack of response or relapse, received PF-00868554 450 milligram (mg) tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 10 morning dose in a fasted state.
|
PF-00868554 700 mg (Cohort B)
n=10 Participants
Participants who did not receive any prior treatment for HCV with an IFN-alpha regimen (with or without RBV) or who discontinued from an IFN-alpha regimen (with or without RBV) after less than or equal to (\<=) 2 weeks of treatment due to tolerability issues or other reasons, received PF-00868554 700 mg tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 3 evening dose in a fed state.
|
|---|---|---|
|
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
Day 1 (n=10, 10)
|
140275.9 nanogram*hour/milliliter (ng*hr/mL)
Standard Deviation 38990.36
|
198506.9 nanogram*hour/milliliter (ng*hr/mL)
Standard Deviation 79422.27
|
|
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
Day 3 for Cohort B (n=0, 10)
|
NA nanogram*hour/milliliter (ng*hr/mL)
Standard Deviation NA
Data was not collected for this arm at given time point as per planned analysis.
|
291172.4 nanogram*hour/milliliter (ng*hr/mL)
Standard Deviation 184959.54
|
|
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
Day 10 for Cohort A (n=10, 0)
|
139239.7 nanogram*hour/milliliter (ng*hr/mL)
Standard Deviation 94286.82
|
NA nanogram*hour/milliliter (ng*hr/mL)
Standard Deviation NA
Data was not collected for this arm at given time point as per planned analysis.
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 2, 6, 8, 12, 14 hrs postdose on Day 1 for Cohort A, B, pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort APopulation: PP analysis set. 'N' (number of participants analyzed) = participants evaluable for this measure. 'n' = participants evaluable for this measure at specified time points for each arm, respectively. Given the sampling schedule on Day 1 and Day 10 for 450 mg dose in Cohort A, AUClast data was not considered meaningful and hence were not analyzed.
Area under the serum concentration time-curve from zero to the last measured concentration (AUClast). AUClast was evaluated at first dose on Day 1 for Cohort A and B, and at last dose for Cohort A (Day 10) and Cohort B (Day 3).
Outcome measures
| Measure |
PF-00868554 450 mg (Cohort A)
Participants who had a history of unsuccessful treatment for hepatitis C virus (HCV) with an interferon-alpha (IFN-alpha) regimen (with or without ribavirin \[RBV\]) due to lack of response or relapse, received PF-00868554 450 milligram (mg) tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 10 morning dose in a fasted state.
|
PF-00868554 700 mg (Cohort B)
n=10 Participants
Participants who did not receive any prior treatment for HCV with an IFN-alpha regimen (with or without RBV) or who discontinued from an IFN-alpha regimen (with or without RBV) after less than or equal to (\<=) 2 weeks of treatment due to tolerability issues or other reasons, received PF-00868554 700 mg tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 3 evening dose in a fed state.
|
|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Day 1 (n=0, 10)
|
—
|
239697.9 ng*hr/mL
Standard Deviation 93463.98
|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Day 3 for Cohort B (n=0, 10)
|
—
|
344075.5 ng*hr/mL
Standard Deviation 248444.34
|
SECONDARY outcome
Timeframe: Pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort APopulation: PP analysis set. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. Results are reported for Cohort B at Day 3. Due to differences in sampling schedules between Cohort A and B, AUC (0 - ∞) data was not considered meaningful and hence were not analyzed on Day 10 for Cohort A.
AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). AUC (0 - ∞) was evaluated at last dose for Cohort A (Day 10) and Cohort B (Day 3).
Outcome measures
| Measure |
PF-00868554 450 mg (Cohort A)
Participants who had a history of unsuccessful treatment for hepatitis C virus (HCV) with an interferon-alpha (IFN-alpha) regimen (with or without ribavirin \[RBV\]) due to lack of response or relapse, received PF-00868554 450 milligram (mg) tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 10 morning dose in a fasted state.
|
PF-00868554 700 mg (Cohort B)
n=10 Participants
Participants who did not receive any prior treatment for HCV with an IFN-alpha regimen (with or without RBV) or who discontinued from an IFN-alpha regimen (with or without RBV) after less than or equal to (\<=) 2 weeks of treatment due to tolerability issues or other reasons, received PF-00868554 700 mg tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 3 evening dose in a fed state.
|
|---|---|---|
|
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]
|
—
|
346170.1 ng*hr/mL
Standard Deviation 250370.33
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 2, 6, 8, 12 hours (hrs) postdose on Day 1 for Cohort A and B, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12 hrs post-evening dose on Day 3 for Cohort B, predose, 0.5, 1, 2, 4, 8, 12 hrs postdose on Day 10 for Cohort APopulation: PP analysis set. Here 'n' signifies those participants who were evaluable for this measure at specified time points for each arm, respectively. The Ctau on Day 1 was not necessary for interpretation of the PK data and hence was not analyzed.
Ctau was evaluated at first dose on Day 1 for Cohort A and B, and at last dose for Cohort A (Day 10) and Cohort B (Day 3).
Outcome measures
| Measure |
PF-00868554 450 mg (Cohort A)
n=10 Participants
Participants who had a history of unsuccessful treatment for hepatitis C virus (HCV) with an interferon-alpha (IFN-alpha) regimen (with or without ribavirin \[RBV\]) due to lack of response or relapse, received PF-00868554 450 milligram (mg) tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 10 morning dose in a fasted state.
|
PF-00868554 700 mg (Cohort B)
n=10 Participants
Participants who did not receive any prior treatment for HCV with an IFN-alpha regimen (with or without RBV) or who discontinued from an IFN-alpha regimen (with or without RBV) after less than or equal to (\<=) 2 weeks of treatment due to tolerability issues or other reasons, received PF-00868554 700 mg tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 3 evening dose in a fed state.
|
|---|---|---|
|
Plasma Concentration at The End of Dosing Interval (Ctau)
Day 3 for Cohort B (n=0, 10)
|
NA ng/mL
Standard Deviation NA
Data was not collected for this arm at given time point as per planned analysis.
|
6572.0 ng/mL
Standard Deviation 9550.56
|
|
Plasma Concentration at The End of Dosing Interval (Ctau)
Day 10 for Cohort A (n=10, 0)
|
1435.2 ng/mL
Standard Deviation 3065.84
|
NA ng/mL
Standard Deviation NA
Data was not collected for this arm at given time point as per planned analysis.
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 2, 6, 8, 12, 14 hrs postdose on Day 1 for Cohort A, B, pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort APopulation: PP analysis set included all participants who took PF-00866554 and had sufficient plasma concentration data to facilitate calculation of the PK parameters. Here 'n' signifies those participants who were evaluable for this measure at specified time points for each arm, respectively.
Cmax was evaluated at first dose on Day 1 for Cohort A and B, and at last dose for Cohort A (Day 10) and Cohort B (Day 3).
Outcome measures
| Measure |
PF-00868554 450 mg (Cohort A)
n=10 Participants
Participants who had a history of unsuccessful treatment for hepatitis C virus (HCV) with an interferon-alpha (IFN-alpha) regimen (with or without ribavirin \[RBV\]) due to lack of response or relapse, received PF-00868554 450 milligram (mg) tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 10 morning dose in a fasted state.
|
PF-00868554 700 mg (Cohort B)
n=10 Participants
Participants who did not receive any prior treatment for HCV with an IFN-alpha regimen (with or without RBV) or who discontinued from an IFN-alpha regimen (with or without RBV) after less than or equal to (\<=) 2 weeks of treatment due to tolerability issues or other reasons, received PF-00868554 700 mg tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 3 evening dose in a fed state.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax)
Day 1 (n=10, 10)
|
44688.1 ng/mL
Standard Deviation 13542.30
|
38734.5 ng/mL
Standard Deviation 14464.27
|
|
Maximum Observed Plasma Concentration (Cmax)
Day 3 for Cohort B (n=0, 10)
|
NA ng/mL
Standard Deviation NA
Data was not collected for this arm at given time point as per planned analysis.
|
50274.1 ng/mL
Standard Deviation 22297.74
|
|
Maximum Observed Plasma Concentration (Cmax)
Day 10 for Cohort A (n=10, 0)
|
42859.7 ng/mL
Standard Deviation 16697.78
|
NA ng/mL
Standard Deviation NA
Data was not collected for this arm at given time point as per planned analysis.
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 2, 6, 8, 12, 14 hrs postdose on Day 1 for Cohort A, B, pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort APopulation: PP analysis set included all participants who took PF-00866554 and had sufficient plasma concentration data to facilitate calculation of the PK parameters. Here 'n' signifies those participants who were evaluable for this measure at specified time points for each arm, respectively.
Tmax was evaluated at first dose on Day 1 for Cohort A and B, and at last dose for Cohort A (Day 10) and Cohort B (Day 3).
Outcome measures
| Measure |
PF-00868554 450 mg (Cohort A)
n=10 Participants
Participants who had a history of unsuccessful treatment for hepatitis C virus (HCV) with an interferon-alpha (IFN-alpha) regimen (with or without ribavirin \[RBV\]) due to lack of response or relapse, received PF-00868554 450 milligram (mg) tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 10 morning dose in a fasted state.
|
PF-00868554 700 mg (Cohort B)
n=10 Participants
Participants who did not receive any prior treatment for HCV with an IFN-alpha regimen (with or without RBV) or who discontinued from an IFN-alpha regimen (with or without RBV) after less than or equal to (\<=) 2 weeks of treatment due to tolerability issues or other reasons, received PF-00868554 700 mg tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 3 evening dose in a fed state.
|
|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Day 1 (n=10, 10)
|
0.750 hours
Interval 0.5 to 2.0
|
2.000 hours
Interval 1.0 to 2.0
|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Day 3 for Cohort B (n=0, 10)
|
NA hours
Data was not collected for this arm at given time point as per planned analysis.
|
2.000 hours
Interval 1.0 to 4.0
|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Day 10 for Cohort A (n=10, 0)
|
1.000 hours
Interval 0.5 to 2.0
|
NA hours
Data was not collected for this arm at given time point as per planned analysis.
|
SECONDARY outcome
Timeframe: Pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort APopulation: PP analysis set. 'N' (number of participants analyzed) = participants evaluable for this measure. Results are reported for Cohort B at Day 3. Due to limited sampling, time interval over which plasma concentrations were measured after final dose was too short relative to projected t1/2. Therefore, t1/2 estimates were not calculated on Day 10.
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Half-life was evaluated at last dose for Cohort A (Day 10) and Cohort B (Day 3).
Outcome measures
| Measure |
PF-00868554 450 mg (Cohort A)
Participants who had a history of unsuccessful treatment for hepatitis C virus (HCV) with an interferon-alpha (IFN-alpha) regimen (with or without ribavirin \[RBV\]) due to lack of response or relapse, received PF-00868554 450 milligram (mg) tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 10 morning dose in a fasted state.
|
PF-00868554 700 mg (Cohort B)
n=10 Participants
Participants who did not receive any prior treatment for HCV with an IFN-alpha regimen (with or without RBV) or who discontinued from an IFN-alpha regimen (with or without RBV) after less than or equal to (\<=) 2 weeks of treatment due to tolerability issues or other reasons, received PF-00868554 700 mg tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 3 evening dose in a fed state.
|
|---|---|---|
|
Plasma Decay Half-Life (t1/2)
|
—
|
7.468 hours
Standard Deviation 1.3235
|
Adverse Events
PF-00868554 450 mg (Cohort A)
PF-00868554 700 mg (Cohort B)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
PF-00868554 450 mg (Cohort A)
n=10 participants at risk
Participants who had a history of unsuccessful treatment for hepatitis C virus (HCV) with an interferon-alpha (IFN-alpha) regimen (with or without ribavirin \[RBV\]) due to lack of response or relapse, received PF-00868554 450 milligram (mg) tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 10 morning dose in a fasted state.
|
PF-00868554 700 mg (Cohort B)
n=10 participants at risk
Participants who did not receive any prior treatment for HCV with an IFN-alpha regimen (with or without RBV) or who discontinued from an IFN-alpha regimen (with or without RBV) after less than or equal to (\<=) 2 weeks of treatment due to tolerability issues or other reasons, received PF-00868554 700 mg tablet orally twice daily, every 12 hours from Day 1 morning dose to Day 3 evening dose in a fed state.
|
|---|---|---|
|
Ear and labyrinth disorders
Ear pain
|
10.0%
1/10
|
0.00%
0/10
|
|
Eye disorders
Vision blurred
|
0.00%
0/10
|
10.0%
1/10
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/10
|
10.0%
1/10
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/10
|
10.0%
1/10
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/10
|
20.0%
2/10
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/10
|
10.0%
1/10
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/10
|
20.0%
2/10
|
|
Gastrointestinal disorders
Dyspepsia
|
40.0%
4/10
|
10.0%
1/10
|
|
Gastrointestinal disorders
Eructation
|
10.0%
1/10
|
10.0%
1/10
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/10
|
10.0%
1/10
|
|
Gastrointestinal disorders
Stomach discomfort
|
10.0%
1/10
|
0.00%
0/10
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/10
|
10.0%
1/10
|
|
General disorders
Pain
|
10.0%
1/10
|
20.0%
2/10
|
|
Infections and infestations
Rhinitis
|
0.00%
0/10
|
10.0%
1/10
|
|
Infections and infestations
Tinea pedis
|
20.0%
2/10
|
0.00%
0/10
|
|
Injury, poisoning and procedural complications
Contusion
|
10.0%
1/10
|
0.00%
0/10
|
|
Injury, poisoning and procedural complications
Skin laceration
|
0.00%
0/10
|
10.0%
1/10
|
|
Metabolism and nutrition disorders
Anorexia
|
10.0%
1/10
|
0.00%
0/10
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
10.0%
1/10
|
0.00%
0/10
|
|
Nervous system disorders
Dysgeusia
|
20.0%
2/10
|
0.00%
0/10
|
|
Nervous system disorders
Headache
|
40.0%
4/10
|
30.0%
3/10
|
|
Renal and urinary disorders
Haematuria
|
10.0%
1/10
|
0.00%
0/10
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.0%
1/10
|
10.0%
1/10
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
10.0%
1/10
|
0.00%
0/10
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
10.0%
1/10
|
20.0%
2/10
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
20.0%
2/10
|
20.0%
2/10
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
20.0%
2/10
|
0.00%
0/10
|
|
Skin and subcutaneous tissue disorders
Erythema
|
10.0%
1/10
|
0.00%
0/10
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/10
|
20.0%
2/10
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
0.00%
0/10
|
10.0%
1/10
|
|
Skin and subcutaneous tissue disorders
Rash macular
|
10.0%
1/10
|
0.00%
0/10
|
Additional Information
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