Study of INT-747 in Patients With Diabetes and Presumed NAFLD

Fatty Liver Clinical Trial

Official title:

An Exploratory Study of INT-747 in Patients With Type 2 Diabetes Mellitus and Presumed Nonalcoholic Fatty Liver Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00501592
• Other study ID #: 747-203
• Status: Completed
• Phase: Phase 2
• First received: July 13, 2007
• Last updated: April 17, 2012
• Start date: July 2007
• Est. completion date: April 2009

Study information

• Verified date: April 2012
• Source: Intercept Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The primary objectives of this study are to assess, in patients with Type 2 diabetes mellitus (DM) and presumed nonalcoholic fatty liver disease (NAFLD), the following:

• The safety and tolerability of multiple doses of INT 747;

• The effects of 2 dose levels (25 mg and 50 mg) of INT 747 on insulin resistance and glucose homeostasis;

• Effects of INT-747 on hepatocellular function as measured by assessment of liver enzymes and biochemical markers of hepatic and metabolic function and inflammation, and;

• Trough concentrations of INT-747 and its metabolites, glyco 6-ethyl chenodeoxycholic acid (6-EDCA) and tauro 6-ECDCA.

Description:

This is a multi-center, double-blind, randomized, placebo-controlled, multiple-dose, parallel-group study. Three (3) cohorts of 12 patients each will receive either placebo, 25 mg INT-747, or 50 mg INT-747 by mouth daily for 6 weeks.

The primary objective of assessing changes in insulin resistance and glucose homeostasis will be attained by performing a euglycemic clamp procedure at baseline (Day 0) and at the end of 6 weeks of treatment (Day 43). Other endpoints will be evaluated by monitoring adverse experiences; vital signs; clinical laboratory values; plasma drug and metabolite concentrations; and general health and well-being.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: April 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Type 2 diabetes, defined by the American Diabetes Association (ADA), as one of the following criteria:

• Symptoms of diabetes plus casual plasma glucose concentration >200 mg/dL (11.1 mmol/L) or

• Fasting plasma glucose >126 mg/dL (7.0 mmol/L) or

• 2-hour post-load glucose >200 mg/dL (11.1 mmol/L) during a 75 g oral glucose tolerance test (GTT).

• Presumed NAFLD, defined by one of the following criteria:

• Alanine aminotransferase (ALT) =47 U/L for females and =56 U/L for males

• Aspartate aminotransferase (AST) =47 U/L for females and =60 U/L for males

• Enlarged liver (demonstrated by ultrasound or other imaging technique)

• Diagnostic histological findings shown on prior biopsy (in the last 5 years).

Exclusion Criteria:

• Bilirubin >2 × ULN

• ALT >155 U/L for females and >185 U/L for males.

• AST >155 U/L for females and >200 U/L for males.

• Patients taking any antidiabetic medications, with the exception of metformin and sulfonylureas. If the HbA1c is <11%, patients may be enrolled who have been withdrawn from all other diabetic medications as specified in the protocol, at the discretion of the Principal Investigator.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Diabetes Mellitus, Type II
• Fatty Liver

Intervention

Drug:
• INT-747
25 mg by mouth once daily, 50 mg by mouth once daily
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Profil Institute for Clinical Research, Inc.	Chula Vista	California
United States	Virginia Commonwelath University	Richmond	Virginia
United States	Diabetes & Glandular Disease Research Associates, Inc.	San Antonio	Texas
United States	UC San Diego VAMC	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Intercept Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin Resistance and Glucose Homeostasis	The primary objective of assessing changes in insulin resistance and glucose homeostasis will be attained by performing a euglycemic clamp procedure at baseline (Day 0) and at the end of 6 weeks of treatment (Day 43).	baseline and 6 weeks	No
Secondary	Hepatocellular Function	Hepatocellular function as measured by assessment of liver enzymes and biochemical markers of hepatic and metabolic function	baseline and 6 weeks	Yes