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

Sponsor:	Intercept Pharmaceuticals
Information provided by (Responsible Party):	Intercept Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00501592

Purpose

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.

Condition	Intervention	Phase
Diabetes Mellitus, Type II Fatty Liver	Drug: INT-747 Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	An Exploratory Study of INT-747 in Patients With Type 2 Diabetes Mellitus and Presumed Nonalcoholic Fatty Liver Disease

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Diabetes Medicines Diabetes Type 2 Liver Diseases

U.S. FDA Resources

Further study details as provided by Intercept Pharmaceuticals:

Primary Outcome Measures:

Insulin Resistance and Glucose Homeostasis [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
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).

Secondary Outcome Measures:

Hepatocellular Function [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: Yes ]
Hepatocellular function as measured by assessment of liver enzymes and biochemical markers of hepatic and metabolic function

Enrollment:	64
Study Start Date:	July 2007
Study Completion Date:	April 2009
Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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
Placebo Comparator: Placebo	Drug: Placebo Placebo

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.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00501592

Locations

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

Sponsors and Collaborators

Intercept Pharmaceuticals

Investigators

Study Director:

David A Shapiro, M.D.

Intercept Pharmaceuticals

More Information

No publications provided

Responsible Party:	Intercept Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00501592 History of Changes
Other Study ID Numbers:	747-203
Study First Received:	July 13, 2007
Results First Received:	June 7, 2011
Last Updated:	December 21, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Intercept Pharmaceuticals:

Farnesoid X receptor agonist
Metabolic Disorder
Diabetes
NAFLD

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Fatty Liver
Glucose Metabolism Disorders

Metabolic Diseases
Endocrine System Diseases
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on February 12, 2012