Study of INT-747 in Patients With Diabetes and Presumed NAFLD
Primary Purpose
Diabetes Mellitus, Type II, Fatty Liver
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
INT-747
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type II focused on measuring Farnesoid X receptor agonist, Metabolic Disorder, Diabetes, NAFLD
Eligibility 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11%, patients may be enrolled who have been withdrawn from all other diabetic medications as specified in the protocol, at the discretion of the Principal Investigator.
Sites / Locations
- Profil Institute for Clinical Research, Inc.
- UC San Diego VAMC
- Diabetes & Glandular Disease Research Associates, Inc.
- Virginia Commonwelath University
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
25 mg INT-747
50 mg INT-747
Placebo
Arm Description
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
Hepatocellular Function
Hepatocellular function as measured by assessment of liver enzymes and biochemical markers of hepatic and metabolic function
Full Information
NCT ID
NCT00501592
First Posted
July 13, 2007
Last Updated
April 17, 2012
Sponsor
Intercept Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT00501592
Brief Title
Study of INT-747 in Patients With Diabetes and Presumed NAFLD
Official Title
An Exploratory Study of INT-747 in Patients With Type 2 Diabetes Mellitus and Presumed Nonalcoholic Fatty Liver Disease
Study Type
Interventional
2. Study Status
Record Verification Date
April 2012
Overall Recruitment Status
Completed
Study Start Date
July 2007 (undefined)
Primary Completion Date
February 2009 (Actual)
Study Completion Date
April 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Intercept Pharmaceuticals
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type II, Fatty Liver
Keywords
Farnesoid X receptor agonist, Metabolic Disorder, Diabetes, NAFLD
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
64 (Actual)
8. Arms, Groups, and Interventions
Arm Title
25 mg INT-747
Arm Type
Active Comparator
Arm Title
50 mg INT-747
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
INT-747
Intervention Description
25 mg by mouth once daily, 50 mg by mouth once daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Insulin Resistance and Glucose Homeostasis
Description
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 Outcome Measure Information:
Title
Hepatocellular Function
Description
Hepatocellular function as measured by assessment of liver enzymes and biochemical markers of hepatic and metabolic function
Time Frame
baseline and 6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David A Shapiro, M.D.
Organizational Affiliation
Intercept Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Profil Institute for Clinical Research, Inc.
City
Chula Vista
State/Province
California
ZIP/Postal Code
91911
Country
United States
Facility Name
UC San Diego VAMC
City
San Diego
State/Province
California
ZIP/Postal Code
92161
Country
United States
Facility Name
Diabetes & Glandular Disease Research Associates, Inc.
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Virginia Commonwelath University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
23727264
Citation
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.
Results Reference
derived
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Study of INT-747 in Patients With Diabetes and Presumed NAFLD
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