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

Non-alcoholic Fatty Liver Disease (NAFLD) Clinical Trial

Official title:

A Randomized, Multicenter, Double-blind, Placebo-controlled, Parallel-group, 24-week Pilot Study to Assess the Efficacy, Safety and Tolerability of LCQ908 in Patients With Non-alcoholic Fatty Liver Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01811472
• Other study ID #: CLCQ908A2216
• Secondary ID: 2013-000049-38
• Status: Completed
• Phase: Phase 2
• First received: March 12, 2013
• Last updated: January 5, 2016
• Start date: June 2013
• Est. completion date: September 2014

Study information

• Verified date: January 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 74 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease (NAFLD)

Intervention

Drug:
• LCQ908
LCQ908 5 mg, 10 mg, 20 mg tablets
• placebo
Matching placebo of LCQ908 5 mg, 10 mg, 20 mg tablets.

Locations

Country	Name	City	State
United States	Novartis Investigative Site	Gainesville	Florida
United States	Novartis Investigative Site	Honolulu	Hawaii
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Louisville	Kentucky
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Mobile	Alabama
United States	Novartis Investigative Site	Plano	Texas
United States	Novartis Investigative Site	Richmond	Virginia
United States	Novartis Investigative Site	San Diego	California
United States	Novartis Investigative Site	Tamarac	Florida
United States	Novartis Investigative Site	Tupelo	Mississippi

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Percentage of Fat in the Liver as Assessed Using MRI at Week 24	Patients were to undergo MRI three times during the course of the study to assess liver fat. Baseline is defined as the value collected at Week -2 MRI assessment (approximately between Day -7 to -14).	From baseline to week 24	No
Secondary	Change From Baseline in Percentage of Fat in the Liver as Assessed Using MRI at Week 12	Patients were to undergo MRI three times during the course of the study to assess liver fat. Baseline is defined as the value collected at Week -2 MRI assessment (approximately between Day -7 to -14).	From baseline to week 12	No
Secondary	Percentage of Responders at Week 12	The response criteria are defined as: a. A reduction of = 30% from baseline in liver fat b. A reduction of = 50% from baseline in liver fat c. Liver fat content < 10% d. Liver fat content < 5.6%. Percentage is calculated as (m/n)*100 where m: number of patients who are responders. n: number of patients with non-missing percent liver fat at that visit.	At week 12	No
Secondary	Percentage of Responders at Week 24	The response criteria are defined as: a. A reduction of = 30% from baseline in liver fat b. A reduction of = 50% from baseline in liver fat c. Liver fat content < 10% d. Liver fat content < 5.6%. Percentage is calculated as (m/n)*100 where m: number of patients who are responders. n: number of patients with non-missing percent liver fat at that visit.	From baseline to week 24	No
Secondary	Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 6	Change from baseline ALT, AST and GGT values collected post-dose was analyzed using Mixed Model of Repeated Measurements (MMRM). Baseline is defined as the value collected at Week 0 (randomization).; Treatment group and visit were fitted as factors and baseline was fitted as a continuous covariate.	From Baseline to week 6	No
Secondary	Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 12	Change from baseline ALT, AST and GGT values collected post-dose was analyzed using Mixed Model of Repeated Measurements (MMRM). Baseline is defined as the value collected at Week 0 (randomization).; Treatment group and visit were fitted as factors and baseline was fitted as a continuous covariate.	From Baseline to week 12	No
Secondary	Change From Baseline Values for Alanine Aminotransferase (ALT) , Aspartate Aminotransferase (AST) and Gamma-glutamyl Transpeptidase (GGT) to Week 24	Change from baseline ALT, AST and GGT values collected post-dose was analyzed using Mixed Model of Repeated Measurements (MMRM). Baseline is defined as the value collected at Week 0 (randomization).; Treatment group and visit were fitted as factors and baseline was fitted as a continuous covariate.	From Baseline to week 24	No
Secondary	Percentage of Patients With Normalized Liver Enzymes	Normalized liver enzymes defined as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 40 U/L. Normal/High categories at baseline are defined by criteria of normal. Better is defined as high' at baseline and 'normal' post-dose; Same is defined as 'normal' at baseline and 'normal' post-dose or 'high' at baseline and 'high' post-dose; Worse is defined as 'normal' at baseline and 'high' post-dose.	Baseline, week 6, week 12 and week 24	No
Secondary	Percent Change From Baseline in Fasting Triglycerides	Blood samples were collected for a fasting triglycerides (TG) after a 10-hour (overnight) fast.; Adjusted geometric means which is reported are calculated by back-transforming the adjusted means from the model and expressing as a percentage change from baseline. Baseline is defined as the value collected at Week 0 (randomization).	Baseline, 6, 12 and 24 weeks	No
Secondary	Post-prandial Peak Triglycerides Over 0 - 8 Hours	Post-prandial peak triglycerides is reported as maximum triglyceride value over 0-8 hours.; Adjusted geometric means which is reported are calculated by back-transforming the adjusted means from the model. Baseline is defined as the value collected at Week 0 (randomization).	Baseline, 6 and 24 weeks	No
Secondary	Change From Baseline in Body Weight		Baseline, 12 and 24 weeks	No
Secondary	Change From Baseline in Waist Circumference		Baseline, 12 and 24 weeks	No
Secondary	Number of Patients With Adverse Events, Serious Adverse Events (SAEs) and Death as Assessment of Safety and Tolerability		24 weeks	Yes