Trial Outcomes & Findings for A Dose Ranging Study Of PF-00868554 In Combination With PEGASYS And COPEGUS In Patients With Chronic Hepatitis C Genotype 1 Infection (NCT NCT00720434)

NCT ID: NCT00720434

Last Updated: 2013-08-26

Results Overview

Plasma HCV RNA levels were measured using the Roche COBAS Taqman assay (limit of detection: 25 international unit per milliliter \[IU/mL\]). Baseline value calculated as the average of the screening and Day 1 pre-dose measurements.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

Baseline, Week 4

Results posted on

2013-08-26

Participant Flow

Participant milestones

Participant milestones
Measure	PF-00868554 200 mg + pegIFN Alfa-2a/RBV PF-00868554 200 milligram (mg) (2 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegylated interferon alfa-2a (pegIFN alfa-2a) 180 microgram (mcg) subcutaneously once weekly starting from Day 1 and ribavirin (RBV) 1000 mg/day tablet orally in 2 divided doses for participants weighing less than or equal to (\<=) 75 kilogram (kg); 1200 mg/day orally in 2 divided doses for participants weighing greater than (\>) 75 kg.	PF-00868554 300 mg + pegIFN Alfa-2a/RBV PF-00868554 300 mg (3 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.	PF-00868554 500 mg + pegIFN Alfa-2a/RBV PF-00868554 500 mg (5 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.	Placebo + pegIFN Alfa-2a/RBV Placebo matched to PF-00868554 tablets orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.
Double-Blind Period (Week 1-4) STARTED	10	9	8	8
Double-Blind Period (Week 1-4) COMPLETED	10	8	8	8
Double-Blind Period (Week 1-4) NOT COMPLETED	0	1	0	0
Open-Label Period (Week 5-72) STARTED	10	8	8	8
Open-Label Period (Week 5-72) COMPLETED	4	5	4	4
Open-Label Period (Week 5-72) NOT COMPLETED	6	3	4	4

Reasons for withdrawal

Reasons for withdrawal
Measure	PF-00868554 200 mg + pegIFN Alfa-2a/RBV PF-00868554 200 milligram (mg) (2 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegylated interferon alfa-2a (pegIFN alfa-2a) 180 microgram (mcg) subcutaneously once weekly starting from Day 1 and ribavirin (RBV) 1000 mg/day tablet orally in 2 divided doses for participants weighing less than or equal to (\<=) 75 kilogram (kg); 1200 mg/day orally in 2 divided doses for participants weighing greater than (\>) 75 kg.	PF-00868554 300 mg + pegIFN Alfa-2a/RBV PF-00868554 300 mg (3 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.	PF-00868554 500 mg + pegIFN Alfa-2a/RBV PF-00868554 500 mg (5 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.	Placebo + pegIFN Alfa-2a/RBV Placebo matched to PF-00868554 tablets orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.
Double-Blind Period (Week 1-4) Withdrawal by Subject	0	1	0	0
Open-Label Period (Week 5-72) Adverse Event	0	0	0	2
Open-Label Period (Week 5-72) Lost to Follow-up	1	0	0	0
Open-Label Period (Week 5-72) Withdrawal by Subject	1	0	1	0
Open-Label Period (Week 5-72) Other	4	3	3	2

Baseline Characteristics

A Dose Ranging Study Of PF-00868554 In Combination With PEGASYS And COPEGUS In Patients With Chronic Hepatitis C Genotype 1 Infection

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PF-00868554 200 mg + pegIFN Alfa-2a/RBV n=10 Participants PF-00868554 200 milligram (mg) (2 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegylated interferon alfa-2a (pegIFN alfa-2a) 180 microgram (mcg) subcutaneously once weekly starting from Day 1 and ribavirin (RBV) 1000 mg/day tablet orally in 2 divided doses for participants weighing less than or equal to (\<=) 75 kilogram (kg); 1200 mg/day orally in 2 divided doses for participants weighing greater than (\>) 75 kg.	PF-00868554 300 mg + pegIFN Alfa-2a/RBV n=9 Participants PF-00868554 300 mg (3 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.	PF-00868554 500 mg + pegIFN Alfa-2a/RBV n=8 Participants PF-00868554 500 mg (5 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.	Placebo + pegIFN Alfa-2a/RBV n=8 Participants Placebo matched to PF-00868554 tablets orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.	Total n=35 Participants Total of all reporting groups
Age, Customized 18 to 44 years	5 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	1 participants n=4 Participants	12 participants n=21 Participants
Age, Customized 45 to 64 years	5 participants n=5 Participants	6 participants n=7 Participants	5 participants n=5 Participants	7 participants n=4 Participants	23 participants n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	7 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants	17 Participants n=21 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants	3 Participants n=4 Participants	18 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of study drug and had both baseline and at least 1 valid post-baseline endpoint measurements for HCV viral load. Here 'n' signifies participants evaluable for this measure at specified time points for each arm, respectively.

Outcome measures

Outcome measures
Measure	PF-00868554 200 mg + pegIFN Alfa-2a/RBV n=10 Participants PF-00868554 200 milligram (mg) (2 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegylated interferon alfa-2a (pegIFN alfa-2a) 180 microgram (mcg) subcutaneously once weekly starting from Day 1 and ribavirin (RBV) 1000 mg/day tablet orally in 2 divided doses for participants weighing less than or equal to (\<=) 75 kilogram (kg); 1200 mg/day orally in 2 divided doses for participants weighing greater than (\>) 75 kg.	PF-00868554 300 mg + pegIFN Alfa-2a/RBV n=9 Participants PF-00868554 300 mg (3 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.	PF-00868554 500 mg + pegIFN Alfa-2a/RBV n=8 Participants PF-00868554 500 mg (5 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.	Placebo + pegIFN Alfa-2a/RBV n=8 Participants Placebo matched to PF-00868554 tablets orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 4 - Full Analysis Set Baseline (n=10, 9, 8, 8)	6.38843 log10 IU/mL Standard Deviation 0.483283	6.67823 log10 IU/mL Standard Deviation 0.472198	6.66254 log10 IU/mL Standard Deviation 0.563548	6.42047 log10 IU/mL Standard Deviation 0.499677
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 4 - Full Analysis Set Change at Week 4 (n=10, 8, 8, 8)	-4.45887 log10 IU/mL Standard Deviation 1.422134	-4.64646 log10 IU/mL Standard Deviation 1.982243	-3.61918 log10 IU/mL Standard Deviation 2.488935	-2.10239 log10 IU/mL Standard Deviation 1.429056

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: Modified Analysis Set: subset of FAS that included all participants who completed the Week 4 visit.

Plasma HCV RNA levels were measured using the Roche COBAS Taqman assay (limit of detection: 25 IU/mL). Baseline value calculated as the average of the screening and Day 1 pre-dose measurements.

Outcome measures

Outcome measures
Measure	PF-00868554 200 mg + pegIFN Alfa-2a/RBV n=10 Participants PF-00868554 200 milligram (mg) (2 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegylated interferon alfa-2a (pegIFN alfa-2a) 180 microgram (mcg) subcutaneously once weekly starting from Day 1 and ribavirin (RBV) 1000 mg/day tablet orally in 2 divided doses for participants weighing less than or equal to (\<=) 75 kilogram (kg); 1200 mg/day orally in 2 divided doses for participants weighing greater than (\>) 75 kg.	PF-00868554 300 mg + pegIFN Alfa-2a/RBV n=8 Participants PF-00868554 300 mg (3 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.	PF-00868554 500 mg + pegIFN Alfa-2a/RBV n=8 Participants PF-00868554 500 mg (5 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.	Placebo + pegIFN Alfa-2a/RBV n=8 Participants Placebo matched to PF-00868554 tablets orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 4 - Modified Analysis Set	-4.45887 log10 IU/mL Standard Deviation 1.422134	-4.64646 log10 IU/mL Standard Deviation 1.982243	-3.61918 log10 IU/mL Standard Deviation 2.488935	-2.10239 log10 IU/mL Standard Deviation 1.429056

SECONDARY outcome

Timeframe: Week 4, 12, 48, 60, 72

Population: Modified Analysis Set: subset of FAS that included all participants who completed the Week 4 visit.

Proportion of participants achieving undetectable plasma HCV RNA at Week 4 (rapid virologic response), at Week 12 (early virologic response), at Week 48 (end of treatment response), at Week 60 (sustained virologic response; 12 weeks after cessation of therapy), at Week 72 (sustained virologic response; 24 weeks after cessation of therapy) were summarized. Undetectable viral load was defined as HCV RNA \<25 IU/mL.

Outcome measures

Outcome measures
Measure	PF-00868554 200 mg + pegIFN Alfa-2a/RBV n=10 Participants PF-00868554 200 milligram (mg) (2 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegylated interferon alfa-2a (pegIFN alfa-2a) 180 microgram (mcg) subcutaneously once weekly starting from Day 1 and ribavirin (RBV) 1000 mg/day tablet orally in 2 divided doses for participants weighing less than or equal to (\<=) 75 kilogram (kg); 1200 mg/day orally in 2 divided doses for participants weighing greater than (\>) 75 kg.	PF-00868554 300 mg + pegIFN Alfa-2a/RBV n=8 Participants PF-00868554 300 mg (3 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.	PF-00868554 500 mg + pegIFN Alfa-2a/RBV n=8 Participants PF-00868554 500 mg (5 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.	Placebo + pegIFN Alfa-2a/RBV n=8 Participants Placebo matched to PF-00868554 tablets orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.
Proportion of Participants Achieving Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Week 4	0.6000 proportion of participants Interval 0.2624 to 0.8784	0.7500 proportion of participants Interval 0.3491 to 0.9681	0.6250 proportion of participants Interval 0.2449 to 0.9148	0.0000 proportion of participants Interval 0.0 to 0.3694
Proportion of Participants Achieving Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Week 12	0.8000 proportion of participants Interval 0.4439 to 0.9748	0.8750 proportion of participants Interval 0.4735 to 0.9968	0.6250 proportion of participants Interval 0.2449 to 0.9148	0.5000 proportion of participants Interval 0.157 to 0.843
Proportion of Participants Achieving Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Week 48	0.6000 proportion of participants Interval 0.2624 to 0.8784	0.7500 proportion of participants Interval 0.3491 to 0.9681	0.6250 proportion of participants Interval 0.2449 to 0.9148	0.5000 proportion of participants Interval 0.157 to 0.843
Proportion of Participants Achieving Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Week 60	0.3000 proportion of participants Interval 0.0667 to 0.6525	0.5000 proportion of participants Interval 0.157 to 0.843	0.5000 proportion of participants Interval 0.157 to 0.843	0.5000 proportion of participants Interval 0.157 to 0.843
Proportion of Participants Achieving Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Week 72	0.3000 proportion of participants Interval 0.0667 to 0.6525	0.5000 proportion of participants Interval 0.157 to 0.843	0.5000 proportion of participants Interval 0.157 to 0.843	0.5000 proportion of participants Interval 0.157 to 0.843

SECONDARY outcome

Timeframe: Week 4, 12, 48, 72

Population: FAS included all randomized participants who received at least 1 dose of study drug and had both baseline and at least 1 valid post-baseline endpoint measurements for HCV viral load. Here 'n' signifies participants evaluable for this measure at specified time points for each arm, respectively.

Outcome measures

Outcome measures
Measure	PF-00868554 200 mg + pegIFN Alfa-2a/RBV n=10 Participants PF-00868554 200 milligram (mg) (2 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegylated interferon alfa-2a (pegIFN alfa-2a) 180 microgram (mcg) subcutaneously once weekly starting from Day 1 and ribavirin (RBV) 1000 mg/day tablet orally in 2 divided doses for participants weighing less than or equal to (\<=) 75 kilogram (kg); 1200 mg/day orally in 2 divided doses for participants weighing greater than (\>) 75 kg.	PF-00868554 300 mg + pegIFN Alfa-2a/RBV n=9 Participants PF-00868554 300 mg (3 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.	PF-00868554 500 mg + pegIFN Alfa-2a/RBV n=8 Participants PF-00868554 500 mg (5 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.	Placebo + pegIFN Alfa-2a/RBV n=8 Participants Placebo matched to PF-00868554 tablets orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.
Alanine Aminotransferase (ALT) Levels Week 4 (n=10, 8, 8, 8)	31.1 IU/L Standard Deviation 12.74	28.5 IU/L Standard Deviation 13.60	51.6 IU/L Standard Deviation 19.45	47.1 IU/L Standard Deviation 27.68
Alanine Aminotransferase (ALT) Levels Week 12 (n=10, 7, 8, 8)	32.9 IU/L Standard Deviation 15.26	29.4 IU/L Standard Deviation 11.12	42.5 IU/L Standard Deviation 15.09	35.6 IU/L Standard Deviation 19.10
Alanine Aminotransferase (ALT) Levels Week 48 (n=6, 6, 5, 4)	35.2 IU/L Standard Deviation 30.80	25.7 IU/L Standard Deviation 12.61	24.4 IU/L Standard Deviation 19.26	148.8 IU/L Standard Deviation 248.26
Alanine Aminotransferase (ALT) Levels Week 72 (n=6, 5, 5, 4)	46.0 IU/L Standard Deviation 40.54	34.0 IU/L Standard Deviation 27.90	21.8 IU/L Standard Deviation 14.20	21.5 IU/L Standard Deviation 12.77

SECONDARY outcome

Timeframe: 1, 2 and 6 hours post-dose on Day 1; 0 hour (pre-dose) on Day 7, 14, 21; 0 hour (pre-dose), 2, 6 hours post-dose on Day 28

Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.

Outcome measures

Outcome data not reported

Adverse Events

PF-00868554 200 mg + pegIFN Alfa-2a/RBV

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

PF-00868554 300 mg + pegIFN Alfa-2a/RBV

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

PF-00868554 500 mg + pegIFN Alfa-2a/RBV

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Placebo + pegIFN Alfa-2a/RBV

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	PF-00868554 200 mg + pegIFN Alfa-2a/RBV n=10 participants at risk PF-00868554 200 milligram (mg) (2 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegylated interferon alfa-2a (pegIFN alfa-2a) 180 microgram (mcg) subcutaneously once weekly starting from Day 1 and ribavirin (RBV) 1000 mg/day tablet orally in 2 divided doses for participants weighing less than or equal to (\<=) 75 kilogram (kg); 1200 mg/day orally in 2 divided doses for participants weighing greater than (\>) 75 kg.	PF-00868554 300 mg + pegIFN Alfa-2a/RBV n=9 participants at risk PF-00868554 300 mg (3 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.	PF-00868554 500 mg + pegIFN Alfa-2a/RBV n=8 participants at risk PF-00868554 500 mg (5 PF-00868554 100 mg tablets) orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.	Placebo + pegIFN Alfa-2a/RBV n=8 participants at risk Placebo matched to PF-00868554 tablets orally twice daily in combination with standard of care during Week 1 to 4 in blinded treatment period, followed by standard of care as per investigator's discretion up to Week 48, then off-treatment up to Week 72 in open-label period. Standard of care included pegIFN alfa-2a 180 mcg subcutaneously once weekly starting from Day 1 and RBV 1000 mg/day tablet orally in 2 divided doses for participants weighing \<=75 kg; 1200 mg/day orally in 2 divided doses for participants weighing \>75 kg.
Endocrine disorders Thyroiditis	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/9 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	12.5% 1/8 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Gait disturbance	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/9 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	12.5% 1/8 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood creatinine increased	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.1% 1/9 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic gastric cancer	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/9 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	12.5% 1/8 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Confusional state	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/9 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	12.5% 1/8 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.1% 1/9 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/9 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	12.5% 1/8 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events

Additional Information

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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