A Study of RO5093151 in Patients With Non-Alcoholic Fatty Liver Disease

Study Overview
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Brief Summary
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This multi-center, double-blind, randomized, placebo-controlled study will evaluate the change in liver fat content, pharmacokinetics and safety of RO5093151 in patients with non-alcoholic fatty liver disease. Patients will be randomized to receive either daily oral doses of RO5093151 or matching placebo. The anticipated time on study treatment is 12 weeks.

Official Title
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Multi-center, Double-blind, Randomized, Placebo-controlled Study of Selective 11 Beta-HSD1 Inhibition With RO5093151 for 12 Weeks to Investigate Efficacy, Safety and Pharmacokinetics of RO5093151 in Non-alcoholic Fatty Liver Disease and Its Metabolic Consequences.

Conditions
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Fatty Liver, Non-alcoholic Fatty Liver Disease, NAFLD

Intervention / Treatment
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* Drug: Placebo
* Drug: RO5093151


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, 35-65 years of age Hepatic steatosis assessed by magnetic resonance spectroscopy (MRS) with liver fat >5.56% at screening Body mass index (BMI) >27 kg/m2 at screening Insulin resistance assessed by homeostatic model assessment-insulin resistance (HOMA-IR) > 2.5 at screening Agreement to maintain prior diet and exercise habits during the full course of study Exclusion Criteria: History of diabetes mellitus based on World Health Organization (WHO) criteria Known polycystic ovary syndrome Other liver disease e.g. chronic viral hepatitis, alcoholic liver disease, hemachromatosis, cirrhosis Known autoimmune disease or chronic inflammatory disease Myocardial infarction or stroke within 6 months prior to screening Patients taking any anti-diabetic and/or weight-lowering medication currently or within the previous 3 months before screening

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 65 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: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: RO5093151<br>* Oral daily doses for 12 weeks<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* Oral daily doses for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of liver fat content measured by magnetic resonance spectroscopy (MRS) |  | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in insulin resistance assessed by hyperinsulinemic euglycemic clamp |  | Week 12 | 
| Change in endogenous glucose production assessed by hyperinsulinemic euglycemic clamp |  | Week 12 | 
| Pharmacokinetic measures (max and min concentration, clearance, half-life, etc) |  | Week 12 | 
| Safety (incidence and nature of adverse events) |  | Week 12 |