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

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

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.

Study Overview

• Status: Completed
• Conditions: Fatty Liver; Diabetes Mellitus, Type II
• Intervention / Treatment: Drug: Placebo; Drug: INT-747

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
      • Profil Institute for Clinical Research, Inc.
    • San Diego, California, United States, 92161
      • UC San Diego VAMC
  • Texas
    • San Antonio, Texas, United States, 78229
      • Diabetes & Glandular Disease Research Associates, Inc.
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwelath University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Active Comparator: 25 mg INT-747	Drug: INT-747; 25 mg by mouth once daily, 50 mg by mouth once daily
Active Comparator: 50 mg INT-747	Drug: INT-747; 25 mg by mouth once daily, 50 mg by mouth once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hepatocellular Function	Hepatocellular function as measured by assessment of liver enzymes and biochemical markers of hepatic and metabolic function	baseline and 6 weeks

Collaborators and Investigators

• Sponsor: Intercept Pharmaceuticals
• Investigators: Study Director: David A Shapiro, M.D., Intercept Pharmaceuticals

Publications and helpful links

General Publications

• Mudaliar S, Henry RR, Sanyal AJ, Morrow L, Marschall HU, Kipnes M, Adorini L, Sciacca CI, Clopton P, Castelloe E, Dillon P, Pruzanski M, Shapiro D. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology. 2013 Sep;145(3):574-82.e1. doi: 10.1053/j.gastro.2013.05.042. Epub 2013 May 30.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: July 13, 2007
• First Submitted That Met QC Criteria: July 13, 2007
• First Posted (Estimate): July 16, 2007

Study Record Updates

• Last Update Posted (Estimate): April 20, 2012
• Last Update Submitted That Met QC Criteria: April 17, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Diabetes; NAFLD; Metabolic Disorder; Farnesoid X receptor agonist
• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Liver Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Liver
• Other Study ID Numbers: 747-203