Safety And Efficacy Of Oral PF-4136309 In Patients With Chronic Hepatitis C Infection And Abnormal Liver Enzymes

Responder was defined as a participant who experienced reduction in ALT of greater than or equal to (\>=) 30 percent (%) of the baseline value. Baseline ALT value was defined as mean of measurements collected at screening visits 1 and 2 and pre-dose Day 1. ALT levels were determined at central lab.

Time frame: Week 4

Population: Full Analysis Set (FAS): all randomized participants who had a baseline value and at least 1 post-baseline value. Missing data was imputed using last observation carried forward (LOCF).

AUCtau was defined as area under the concentration curve from time zero to end of dosing interval of PF-04136309.

Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post-dose on Day 28

Population: PK parameter analysis set included all enrolled participants treated and who had at least 1 of the PK parameters of interest. Here, Overall Number of Participants Analyzed signifies number of participants who were evaluable for this outcome measure.

p-ERK is a biomarker used to assess bioavailability of PF-04136309. Baseline p-ERK level defined as the last pre-dose measurement.

Time frame: Baseline

Population: FAS population included all randomized participants who had a baseline value and at least 1 post-baseline value; Observed data

Markers of fibrosis assessed in the ELF test comprise hyaluronic acid (HA), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), and amino terminal peptide of pro-collagen III (PIIINP). The HA ranges from 0 to 1000 in ng/mL; the TIMP-1 ranges from 0 to 3000 ng/mL; and the PIIINP tissue ranges from 0 to 151 in nanograms/milliliter (ng/mL). ELF algorithm calculates a discriminant score (DS) specified by DS = -7.412 plus (+) 0.681 times (\*)ln(HA)+ 0.494 \* ln(TIMP1)+ 0.775 \* ln(PIIINP). Results to be reported in discriminant score.

Time frame: Baseline, Week 4

Population: Data for this outcome measure was not collected because there was a change in planned analysis owing to low enrolment number in the study.

After drinking 13ˆC-methacetin, participants breath was collected using a BreathID® collection system for approximately 60 minutes and the ratio of 13ˆCO2:12ˆCO2 were determined to monitor the function of the liver. Results to be reported in ratio.

Time frame: Baseline, Weeks 1 and 4

Population: Data for this outcome measure was not collected because there was a change in planned analysis owing to low enrolment number in the study.

p-ERK is a biomarker used to assess bioavailability of PF-04136309. Baseline p-ERK level defined as the last pre-dose measurement.

Time frame: Baseline, Week 2 and 4

Population: FAS population included all randomized participants who had a baseline value and at least 1 post-baseline value. Missing data was imputed using LOCF.

Baseline ALT value was defined as mean of measurements collected at screening visits 1 and 2 and pre-dose Day 1.

Time frame: Baseline, Weeks 1, 2, 3 and 4

Population: FAS population included all randomized participants who had a baseline value and at least 1 post-baseline value. Missing data was imputed using LOCF.

Baseline AST level was defined as the mean of measurements collected on screening visit 1 and pre-dose Day 1.

Time frame: Baseline, Weeks 1, 2, 3 and 4

Population: FAS population included all randomized participants who had a baseline value and at least 1 post-baseline value. Missing data was imputed using LOCF.

Cmax was defined as maximum observed plasma concentration of PF-04136309.

Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post-dose on Day 28

Population: Pharmacokinetic (PK) parameter analysis set included all enrolled participants treated and who had at least 1 of the PK parameters of interest. Here, Overall Number of Participants Analyzed signifies number of participants who were evaluable for this outcome measure.

AST responder status was defined as a reduction in AST \>= 30% of the baseline value and or normalization. Baseline AST level was defined as the mean of measurements collected on screening visit 1 and pre-dose Day 1. AST levels were determined at central lab.

Time frame: Week 4

Population: FAS population included all randomized participants who had a baseline value and at least 1 post-baseline value. Missing data was imputed using LOCF.

Plasma decay half-life was the time measured for the plasma concentration to decrease by one half.

Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post-dose on Day 28

Population: PK parameter analysis set included all enrolled participants treated and who had at least 1 of the PK parameters of interest. Here, Overall Number of Participants Analyzed signifies number of participants who were evaluable for this outcome measure.

Baseline ALT level was defined as the mean of measurements collected on Screening visits 1 and 2 and pre-dose Day 1.

Time frame: Baseline

Population: FAS population included all randomized participants who had a baseline value and at least 1 post-baseline value; Observed data

Baseline AST level was defined as the mean of measurements collected on screening visit 1 and pre-dose Day 1.

Time frame: Baseline

Population: FAS population included all randomized participants who had a baseline value and at least 1 post-baseline value; Observed data

Tmax was defined as time to reach maximum observed plasma concentration of PF-04136309.

Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post-dose on Day 28

Population: PK parameter analysis set included all enrolled participants treated and who had at least 1 of the PK parameters of interest. Here, Overall Number of Participants Analyzed signifies number of participants who were evaluable for this outcome measure.