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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Diabetes Mellitus, Type II, Fatty Liver

Intervention / Treatment
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* Drug: INT-747
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 25 mg INT-747<br> | Drug: INT-747<br>* 25 mg by mouth once daily, 50 mg by mouth once daily<br>|
| Active Comparator: 50 mg INT-747<br> | Drug: INT-747<br>* 25 mg by mouth once daily, 50 mg by mouth once daily<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Farnesoid X receptor agonist, Metabolic Disorder, Diabetes, NAFLD