Effect of LIK066 on Reduction of Fatty Content in Livers of Obese Patients

This was a a non-confirmatory, multicenter, patient and investigator blinded, randomized, placebo-controlled, parallel group study in patients with non-alcoholic steatohepatitis (NASH).

The study consisted of a 28 day screening period (Day -44 to Day -16), a baseline period of 14 days (Day -15 to Day -1), a treatment period of 12 weeks (Day 1 to Day 84), and a study completion evaluation approximately 28 days after the last drug administration. The patients were advised to maintain their recommended diet during the study.

Patients who met the inclusion/exclusion criteria at screening went to the study site for baseline assessments. All baseline safety evaluation results were available prior to the first dosing.

The study started by enrolling patients into the 150 mg and placebo arms with a randomization ratio of 2:1. After the enrollment of the first 33 patients, the 30 mg arm was added to the study and the randomization ratio changed to a 2:4:1 ratio (150 mg: 30 mg: placebo) to maintain the 2:2:1 ratio across the three groups (150 mg: 30 mg: placebo) at study completion.

Inclusion criteria

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 disease AND ALT greater than or equal to 50 IU/L (males) or greater than or equal to 35 IU/L (females) at screening.

OR

Phenotypic diagnosis of NASH based on presence of ALL three of the following at screening:

• ALT greater than or equal to 50IU/L (males) or greater than or equal to 35 IU/L (females) AND
• BMI greater than or equal to 27 kg/m^2 (in patients with a self-identified race other than Asian) or greater than or equal to 23 kg/m^2 (in patients with a self identified Asian race) AND
• Diagnosis of Type 2 diabetes mellitus by HbA1c: greater than or equal to 6.5 % and less than or equal to 10%
• Patients must weigh no more than 150 kg (330 lbs) to participate in the study.
• Male and female patients 18 years or older at the time of screening visit.

Exclusion criteria

• History or presence of other concomitant liver diseases
• History or current diagnosis of ECG abnormalities
• Use of GLP-1 agonists, SGLT2 inhibitors, TZDs, FXR agonists and any pharmacologically active weight loss drugs within 6 weeks of screening and until end of study
• Patients with contraindications to MRI imaging
• Current or history of significant alcohol consumption
• Clinical evidence of hepatic decompensation or severe liver impairment
• Women of child bearing potential (unless on basic contraception methods)
• Presence of liver cirrhosis