A Study in Adult Patients With Nonalcoholic Steatohepatitis Who Also Have Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to assess the effect of TEV-45478, as compared with placebo, on liver health and liver fat content in patients with T2DM who also have Nonalcoholic Steatohepatitis (NASH).

Official Title
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A 24-Week, Randomized, Double-blind, Placebo-controlled, Efficacy and Safety Study of 80 mg TEV-45478 Once Daily as Treatment in Adult Patients With Nonalcoholic Steatohepatitis (NASH) Who Also Have Type 2 Diabetes Mellitus - GN

Conditions
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Nonalcoholic Steatohepatitis, Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: TEV-45478
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient is female or male and aged 18 to 65 years, inclusive with a history of Type 2 Diabetes Mellitus (T2DM) and on stable medication for diabetes or insulin or a combination thereof for at least 3 months prior to screening. The patient has a NASH Activity Score (NAS) of ≥4, with or without evidence of fibrosis, with a score of at least 1 in steatosis and lobular inflammation the subcomponents of NAS and a hepatocyte ballooning score of at least 1 score based on historical histological evaluation of liver biopsy within 12 months prior to randomization. The patient has a historical diagnosis of NASH, established no more than 12 months prior to randomization based on histology (liver biopsy). The patient has an ALT level at screening between 45 and 105 IU/L, inclusive, for women and between 55 and 120 IU/L, inclusive for men, at one other occasion during the 24-weeks prior to screening. The patient has an MRI determined liver fat fraction of equal to or higher than 6% at Screening Additional criteria apply, please contact the investigator for more information Exclusion Criteria: The patient has a history of chronic liver disease other than NASH eg, chronic or acute hepatitis, autoimmune, viral (A, B, C), genetic hepatitis, drug induced hepatotoxicity, Wilson's disease, alcoholic liver diseases, or any other non-NASH active liver disease. The patient has active cancer or a history of a malignant disease (except basal cell carcinoma of the skin) within 5 years prior to screening or any history of bladder cancer. The patient had an unstable metabolic condition (ie, with a history of weight loss or weight gain of >5 kg within 24 weeks prior to screening) The patient has a history of bariatric surgery within 5 years prior to screening. The patient has received mercaptopurine or azathioprine previously within 1 year prior to screening The patient has taken within 7 days prior to the first dose of study drug (or is anticipated to take during the study) anticholinergic or other drugs known to affect gastrointestinal (GI) motility, proton-pump inhibitors, or other drugs known to affect gastric acidity or use of allopurinol. The patient has received oral antibiotics within the last 4 weeks prior to randomization (day 1). The patient has received treatment within the last 30 days with any drugs known to induce or inhibit endogenous hepatic drug metabolism (eg, barbiturates, phenothiazines, cimetidine, carbamazepine) or anti-coagulant therapy (eg, heparin, warfarin, acenocoumarol). The patient has Type 1 Diabetes Mellitus (T1DM) or poorly controlled T2DM The patient has a body mass index (BMI) <25 kg/m2. The patient has a history of diabetic gastroparesis or has had gastric bypass surgery within the last 5 years. The patient has a history of pancreatitis. The patient has a history of persistent intestinal obstruction, bowel perforation, uncontrolled GI bleed or abdominal abscess or infection or toxic megacolon or inflammatory bowel disease (IBD) The patient has a history of coronary angioplasty, coronary stent placement, coronary bypass surgery, unstable angina, myocardial infarction, transient ischemic events, or stroke within 24-weeks prior to screening. The patient is classified as Class II-IV via New York Heart Association The patient has a history of drug abuse (defined as illicit drug use) or a history of excessive alcohol abuse (defined as regular or daily consumption of more than 2 alcoholic drinks per day for women or 3 alcoholic drinks per day for men) within 1 year prior to the screening visit. Additional criteria apply, please contact the investigator for more information

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TEV-45478<br>80 mg (2x40mg) tablets once daily for up to 24 weeks | Drug: TEV-45478<br>* 80 mg (2x40mg) tablets once daily for up to 24 weeks<br>|
| Placebo Comparator: Placebo<br>Matching placebo | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum Alanine Transaminase (ALT) levels response, defined as ALT value within reference range of <35 IU/L for women and <40 IU/L for men |  | Week 24 | 
| liver fat response, defined as a reduction of ≥6% at week 24 compared to screening by the MRI-Proton Density Fat Fraction (PDFF) |  | Week 24 | 
| Percentage of Participants with Adverse Events |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percent change from baseline in ALT |  | Baseline, Week 24 | 
| percent change from baseline in ALT |  | Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 (or early withdrawal) | 
| percent change from baseline in Aspartate Aminotransferase (AST) |  | Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 (or early withdrawal) | 
| change from baseline in AST |  | Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 (or early withdrawal) | 
| change from baseline in ALT |  | Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 (or early withdrawal) | 
| Change from baseline in glycosylated hemoglobin ((HbA1c) |  | Baseline, Weeks 4, 12, and 24 (or early withdrawal) | 
| Change from baseline in liver fibrosis measured using transient elastography (with Fibroscan) |  | Baseline, Week 24 (or early withdrawal) |