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

Phase 2TerminatedNCT01226797

Pfizer24 enrolled

Overview

This study will evaluate the effect of PF-04136309 in patients with chronic hepatitic C virus infection and abnormal liver enzymes.

Study recruitment was stopped on Dec 15, 2011 due to difficulty in enrolling the targeted number of patients. Subjects currently enrolled into the study will complete the study as per protocol. There were no safety concerns involved in the decision to stop enrollment. The new anticipated Last Subject Last Visit (LSLV) is February 2012.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Hepatitis C, Chronic

Interventions

PlaceboDRUG

Take 4 capsules twice daily 12 hours apart with water. Swallow whole.

PF-04136309DRUG

Take 4 capsules twice daily 12 hours apart with water. Swallow whole.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Chronic HCV infection * ALT \>1.5 but \<10 times upper limit of normal Exclusion Criteria: * Decompensated or severe liver disease defined by one or more of the following criteria: Prior liver biopsy showing cirrhosis. * International Normalized Ratio (INR) greater than or equal to 1.5. * Total bilirubin greater than or equal to 1.5X ULN, or \>2X ULN for unconjugated bilirubin. * Serum albumin below normal. * ALT or aspartate aminotransferase (AST) \>10 x ULN. * Evidence of portal hypertension including splenomegaly, ascites, encephalopathy, and/or esophageal varices. * Presence of human immunodeficiency virus (HIV). * Co-infection with hepatitis B virus (HBV). * Co-infection with Epstein Barr Virus (EBV) and/or Cytomegalovirus (CMV).

Locations (10)

The Chinese University of Hong Kong,

Prince of Wales Hospital, Shatin, New Territories,, Hong Kong, Hong Kong

The University of Hong Kong,

Hong Kong, Hong Kong

Manipal Hospital

Bangalore, Karnataka, India

Outcomes

Primary Outcomes

Percentage of Participants With a Response in Serum Alanine Aminotransferase (ALT) Level at Week 4

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

Secondary Outcomes

Percentage of Participants With a Response in Serum Aspartate Aminotransferase (AST) Level From Baseline at Week 4

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

Change From Baseline in Serum ALT at Weeks 1, 2, 3 and 4

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

Serum ALT at Baseline

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

Change From Baseline in Serum AST at Weeks 1, 2, 3 and 4

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

Serum AST at Baseline

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

Data from ClinicalTrials.gov

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Seth G. S. Medical College & King Edward Memorial Hospital,

Mumbai, Maharashtra, India

Institute of Liver & Biliary Sciences

New Delhi, India

Singapore General Hospital

Singapore, Singapore

Seoul National University Hospital, Department of Internal Medicine

Seoul, South Korea

Severance Hospital, Yonsei University College of Medicine, Division of Gastroenterology

Seoul, South Korea

Chung-Ho Memorial Hospital, Kaohsiung Medical University

Kaohsiung City, Taiwan

National Taiwan University Hospital

Taipei, Taiwan

Time frame: Baseline

Change From Baseline in Methacetin Breath Test (BreathID) at Weeks 1 and 4

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

Change From Baseline in Enhanced Liver Fibrosis Test (ELF) at Week 4

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

Maximum Observed Plasma Concentration (Cmax) of PF-04136309

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

Plasma Decay Half-Life (t1/2) of PF-04136309

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

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-04136309

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

Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04136309

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

Change From Baseline in Phosphorylated Extracellular Signal- Regulated Kinase (p-ERK) Levels at Week 2 and 4

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

Baseline p-ERK

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