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

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 2 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ORAL PF-04136309 500 MG BID IN SUBJECTS WITH CHRONIC HCV INFECTION AND RAISED AMINOTRANSFERASES

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

Study Overview

• Status: Terminated
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Drug: Placebo; Drug: PF-04136309

Detailed Description

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
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hong Kong
  • Hong KOng, Hong Kong
    • The University of Hong Kong,
  • Prince Of Wales Hospital, Shatin, New Territories,, Hong Kong
    • The Chinese University of Hong Kong,
• India
  • New Delhi, India, 110 070
    • Institute of Liver & Biliary Sciences
  • Karnataka
    • Bangalore, Karnataka, India, 560017
      • Manipal Hospital
  • Maharashtra
    • Mumbai, Maharashtra, India, 400 012
      • Seth G. S. Medical College & King Edward Memorial Hospital,
• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital, Department of Internal Medicine
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital, Yonsei University College of Medicine, Division of Gastroenterology
• Singapore
  • Singapore, Singapore, 169608
    • Singapore General Hospital
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Chung-Ho Memorial Hospital, Kaohsiung Medical University
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Take 4 capsules twice daily 12 hours apart with water. Swallow whole.
Active Comparator: PF-04136309	Drug: PF-04136309; Take 4 capsules twice daily 12 hours apart with water. Swallow whole.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	Baseline, Week 4
Maximum Observed Plasma Concentration (Cmax) of PF-04136309	Cmax was defined as maximum observed plasma concentration of PF-04136309.	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.	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.	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.	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.	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.	Baseline

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2011
• Primary Completion (Actual): February 9, 2012
• Study Completion (Actual): February 9, 2012

Study Registration Dates

• First Submitted: October 21, 2010
• First Submitted That Met QC Criteria: October 21, 2010
• First Posted (Estimated): October 22, 2010

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: September 7, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: HCV infection; Chronic HCV infection; raised ALT; transaminitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Chronic Disease; Infections; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic
• Other Study ID Numbers: A9421016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.