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

Primary Purpose

Hepatitis C, Chronic

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
PF-04136309
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C, Chronic focused on measuring Chronic HCV infection, raised ALT, transaminitis, HCV infection

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • The University of Hong Kong,
  • The Chinese University of Hong Kong,
  • Manipal Hospital
  • Seth G. S. Medical College & King Edward Memorial Hospital,
  • Institute of Liver & Biliary Sciences
  • Seoul National University Hospital, Department of Internal Medicine
  • Severance Hospital, Yonsei University College of Medicine, Division of Gastroenterology
  • Singapore General Hospital
  • Chung-Ho Memorial Hospital, Kaohsiung Medical University
  • National Taiwan University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

PF-04136309

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
Serum AST at Baseline
Baseline AST level was defined as the mean of measurements collected on screening visit 1 and pre-dose Day 1.
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.
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.
Maximum Observed Plasma Concentration (Cmax) of PF-04136309
Cmax was defined as maximum observed plasma concentration of PF-04136309.
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.
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 to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04136309
Tmax was defined as time to reach maximum observed plasma concentration of PF-04136309.
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 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.

Full Information

First Posted
October 21, 2010
Last Updated
September 7, 2022
Sponsor
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT01226797
Brief Title
Safety And Efficacy Of Oral PF-4136309 In Patients With Chronic Hepatitis C Infection And Abnormal Liver Enzymes
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Terminated
Why Stopped
See termination reason in detailed description.
Study Start Date
January 17, 2011 (Actual)
Primary Completion Date
February 9, 2012 (Actual)
Study Completion Date
February 9, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, Chronic
Keywords
Chronic HCV infection, raised ALT, transaminitis, HCV infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
PF-04136309
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Take 4 capsules twice daily 12 hours apart with water. Swallow whole.
Intervention Type
Drug
Intervention Name(s)
PF-04136309
Intervention Description
Take 4 capsules twice daily 12 hours apart with water. Swallow whole.
Primary Outcome Measure Information:
Title
Percentage of Participants With a Response in Serum Alanine Aminotransferase (ALT) Level at Week 4
Description
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 Outcome Measure Information:
Title
Percentage of Participants With a Response in Serum Aspartate Aminotransferase (AST) Level From Baseline at Week 4
Description
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
Title
Change From Baseline in Serum ALT at Weeks 1, 2, 3 and 4
Description
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
Title
Serum ALT at Baseline
Description
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
Title
Change From Baseline in Serum AST at Weeks 1, 2, 3 and 4
Description
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
Title
Serum AST at Baseline
Description
Baseline AST level was defined as the mean of measurements collected on screening visit 1 and pre-dose Day 1.
Time Frame
Baseline
Title
Change From Baseline in Methacetin Breath Test (BreathID) at Weeks 1 and 4
Description
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
Title
Change From Baseline in Enhanced Liver Fibrosis Test (ELF) at Week 4
Description
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
Title
Maximum Observed Plasma Concentration (Cmax) of PF-04136309
Description
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
Title
Plasma Decay Half-Life (t1/2) of PF-04136309
Description
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
Title
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-04136309
Description
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
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04136309
Description
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
Title
Change From Baseline in Phosphorylated Extracellular Signal- Regulated Kinase (p-ERK) Levels at Week 2 and 4
Description
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
Title
Baseline p-ERK
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
The University of Hong Kong,
City
Hong KOng
ZIP/Postal Code
0
Country
Hong Kong
Facility Name
The Chinese University of Hong Kong,
City
Prince Of Wales Hospital, Shatin, New Territories,
ZIP/Postal Code
0
Country
Hong Kong
Facility Name
Manipal Hospital
City
Bangalore
State/Province
Karnataka
ZIP/Postal Code
560017
Country
India
Facility Name
Seth G. S. Medical College & King Edward Memorial Hospital,
City
Mumbai
State/Province
Maharashtra
ZIP/Postal Code
400 012
Country
India
Facility Name
Institute of Liver & Biliary Sciences
City
New Delhi
ZIP/Postal Code
110 070
Country
India
Facility Name
Seoul National University Hospital, Department of Internal Medicine
City
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of
Facility Name
Severance Hospital, Yonsei University College of Medicine, Division of Gastroenterology
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of
Facility Name
Singapore General Hospital
City
Singapore
ZIP/Postal Code
169608
Country
Singapore
Facility Name
Chung-Ho Memorial Hospital, Kaohsiung Medical University
City
Kaohsiung
ZIP/Postal Code
807
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
100
Country
Taiwan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A9421016&StudyName=Safety%20And%20Efficacy%20Of%20Oral%20PF-4136309%20In%20Patients%20With%20Chronic%20Hepatitis%20C%20Infection%20And%20Abnormal%20Liver%20Enzymes
Description
To obtain contact information for a study center near you, click here.

Learn more about this trial

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

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