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

Hepatitis C, Chronic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01226797
• Other study ID #: A9421016
• Status: Terminated
• Phase: Phase 2
• Start date: January 17, 2011
• Est. completion date: February 9, 2012

Study information

• Verified date: September 2022
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: February 9, 2012
• Est. primary completion date: February 9, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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).

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Infections

Intervention

Drug:
• Placebo
Take 4 capsules twice daily 12 hours apart with water. Swallow whole.
• PF-04136309
Take 4 capsules twice daily 12 hours apart with water. Swallow whole.

Locations

Country	Name	City	State
Hong Kong	The University of Hong Kong,	Hong KOng
Hong Kong	The Chinese University of Hong Kong,	Prince Of Wales Hospital, Shatin, New Territories,
India	Manipal Hospital	Bangalore	Karnataka
India	Seth G. S. Medical College & King Edward Memorial Hospital,	Mumbai	Maharashtra
India	Institute of Liver & Biliary Sciences	New Delhi
Korea, Republic of	Seoul National University Hospital, Department of Internal Medicine	Seoul
Korea, Republic of	Severance Hospital, Yonsei University College of Medicine, Division of Gastroenterology	Seoul
Singapore	Singapore General Hospital	Singapore
Taiwan	Chung-Ho Memorial Hospital, Kaohsiung Medical University	Kaohsiung
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

Hong Kong,  India,  Korea, Republic of,  Singapore,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

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