A 12-week randomized, patient and investigator blinded, placebo-controlled, parallel group study to investigate the efficacy of LIK066 in obese patients with non-alcoholic steatohepatitis (NASH)
- Conditions
- NASHnon-alcoholic steatohepatitis10019654
- Registration Number
- NL-OMON44568
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 8
Presence of NASH as demonstrated by one of the following:
either
Histologic confirmed NASH based on liver biopsy obtained 2 years or less before randomization with a fibrosis level of F1, F2 or F3, in the absence of a histological diagnosis of alternative chronic liver diseases AND ALT * 50 IU/L (males) or * 35 IU/L (females) at screening;Or
Phenotypic diagnosis of NASH based on presence of all three of the following at screening:
- ALT * 50 IU/L (males) or * 35 IU/L (females) AND
- BMI * 27 kg/m2 (in patients with a self-identified race other than Asian) or *23 kg/m2 (in patients with a self-identified Asian race) AND
- Diagnosis of Type 2 diabetes mellitus by HbA1C: * 6.5% and * 10%
- Use of GLP-1 agonists such as liraglutide, exenatide, lixisenatide, albiglutide or dulaglutide; SGLT-2 inhibitors such as canagliflozin, empagliflozin or dapagliflozin; Thiazolidinediones (TZDs) such as pioglitazone; FXR agonists such as obeticholic acid (OCA) and any pharmacologically active weight-loss medications such as lorcaserin prior to 6 weeks of screening visit and up to end of study visit
- eGFR * 45ml/min/1.73m2 based on MDRD equation
- Patients on treatment with the following medicines unless they are on a constant dose for *3 months before randomization: anti-diabetic medications, insulin (if *25% change in dose),
beta-blockers, thiazide diuretics, fibrates, statins, niacin, ezetimibe, vitamin E (if doses > 400 IU/day; doses > 800 IU/day are prohibited), thyroid hormone, psychotropic medications, estrogen or estrogen containing birth control
- Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening (significant alcohol consumption is defined as more
than 20 g/day in females and more than 30 g/day in males, on average)
- Presence of cirrhosis on liver biopsy or clinical diagnosis of cirrhosis
- Type I diabetes and uncontrolled diabetes defined as HbAlc > 10 % within 60 days prior to enrollment
- Patients with contraindications to MRI imaging
- For those patients that have had a previous liver biopsy:
Significant weight loss (>15%) or change in clinical status (in the opinion of the investigator) since the diagnostic liver biopsy to screening
- History or presence of other concomitant liver diseases
- Clinical evidence of hepatic decompensation or severe liver impairment
- History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during screening and baseline
- History of inflammatory bowel disease
- History or current diagnosis of ECG abnormalities indicating significant risk of safety for patients participating in the study
- History of ketoacidosis, lactic acidosis, or hyperosmolar coma OR if occurring between Screening Visit and Randomization Visit.
- History of lower limb amputation (including toe amputation) OR if occurring between Screening Visit and Randomization Visit.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Change in circulating alanine aminotransferase (ALT) levels</p><br>
- Secondary Outcome Measures
Name Time Method <p>- Percent (%) Liver fat as measured by Magnetic Resonance Imaging (MRI-PDFF)<br /><br>- Percent change in total body weight<br /><br>- Enhanced liver fibrosis panel (ELF: PIIINP, TIMP-1, and Hyaluronic acid)<br /><br>- Adverse events, safety laboratory tests including basic chemistry profile and<br /><br>liver biochemical tests<br /><br>- Cmax, Tmax, AUClast<br /><br>- Circulating aspartate aminotrasferase (AST) levels</p><br>