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

Intercept Pharmaceuticals64 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Diabetes Mellitus, Type II

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (4)

Profil Institute for Clinical Research, Inc.

Chula Vista, California, United States

UC San Diego VAMC

San Diego, California, United States

Diabetes & Glandular Disease Research Associates, Inc.

San Antonio, Texas, United States

Virginia Commonwelath University

Richmond, Virginia, United States

Outcomes

Primary Outcomes

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).

Time frame: baseline and 6 weeks

Secondary Outcomes

Hepatocellular Function

Hepatocellular function as measured by assessment of liver enzymes and biochemical markers of hepatic and metabolic function