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
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
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).
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
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.