Study to Assess the Efficacy, Safety and Tolerability of LCQ908 in NAFLD Patients

Novartis

Status and phase: Completed; Phase 2

Conditions: Non-alcoholic Fatty Liver Disease (NAFLD)

Treatments: Drug: LCQ908; Drug: placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01811472

CLCQ908A2216

2013-000049-38 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study was to determine whether LCQ908 effectively lowers liver fat, as assessed by MRI and to assess its safety and tolerability profile in subjects with non-alcoholic fatty liver disease (NAFLD).

Enrollment: 52 patients

Sex: All

Ages: 18 to 74 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• History of liver steatosis during the preceding 24 months

• History of fasting TGs > 200 mg/dL (confirmed at screening).

• Liver fat ≥ 10% as determined by the central MRI laboratory.

• Subjects on the following medications can be included if these medications are medically necessary, cannot be stopped and the investigator feels their dose will remain stable for the duration of the double-blind treatment period:

  1. Stable dose of anti-diabetic medications (metformin and/or sulfonylureas) for at least 8 weeks prior to screening.
  2. Stable doses of beta-blockers and thiazide diuretics for at least 8 weeks prior to screening.
  3. Stable doses of fibrates, statins, niacin, ezetimibe for at least 8 weeks prior to screening.
  4. Stable dose of vitamin E in patients taking >200 IU/day for at least 6 months prior to screening.

Exclusion criteria

• Treatment with omega-3-acid ethyl esters or omega-3-polyunsaturated fatty acid (PUFA)-containing supplements > 200 mg per day within 8 weeks of screening.
• Treatment with antiretrovirals, tamoxifen, methotrexate, cyclophosphamide, isotretinoin, bile acid binding resins or pharmacologic doses of oral glucocorticoids (≥10 mg of prednisone per day or equivalent) within 8 weeks of screening.
• ALT or AST > 250 IU/L at the time of screening.
• History/current evidence of heavy alcohol use or alcoholism (> 21 drinks per week in men and > 14 drinks per week in women) over a 2-year period prior to screening.
• Presence of chronic liver disease, such as chronic hepatitis B and/or C, alcoholic liver disease, hemochromatosis, Wilson's disease, known cirrhosis.
• Platelet count <150,000 at screening.
• BMI >45 Kg/m2.

Other protocol defined inclusion/exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

52 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Patients randomized to Placebo arm, received matching placebo to 5 mg, 10 mg and 20 mg pradigstat (LCQ908) once daily for 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.

Treatment:

Drug: placebo

pradigastat (LCQ908) 5mg/10mg

Experimental group

Description:

Patients, randomized to pradigastat 5/10 mg, initially began with pradigastat (LCQ908) 5 mg once daily and then were up-titrated, if pradigastat (LCQ908) 5 mg once daily was tolerated, to pradigastat 10 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.

Treatment:

Drug: LCQ908

pradigastat (LCQ908) 10mg/20mg

Experimental group

Description:

Patients, randomized to pradigastat 10/20 mg, initially began with pradigastat (LCQ908) 10 mg once daily and then were up-titrated, if pradigastat (LCQ908) 10 mg once daily was tolerated, to pradigastat 20 mg once daily at Week 2. Total treatment duration was 24 weeks. Each patient was to receive 3 tablets a day. All patients were required to remain on their American Heart Association (AHA) diet for the entire duration of the study.

Treatment:

Drug: LCQ908