A Pilot Study to Assess the Efficacy and Safety of LCQ908 Alone and in Combination With Fenofibrate or Lovaza® in Patients With Severe Hypertriglyceridemia

A Multicenter, Randomized, Active Comparator, Placebo Controlled, Double-blind Pilot Study to Assess the Efficacy and Safety of LCQ908 Alone and in Combination With Fenofibrate or Lovaza® in Patients With Severe Hypertriglyceridemia

This study is to determine a dose response signal for LCQ908 monotherapy and to assess the efficacy and safety of adding LCQ908 to Lovaza or fenofibrate.

Study Overview

• Status: Completed
• Conditions: Non Familial Chylocmicronemia Syndrome (Non-FCS)
• Intervention / Treatment: Drug: LCQ908; Drug: Placebo of LCQ908; Drug: Placebo of fenofibrate; Drug: Placebo of fish oil; Drug: Fenofibrate; Drug: Fish Oil

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 5H6
      • Novartis Investigative Site
    • Ste-Foy, Quebec, Canada, G1V4M6
      • Novartis Investigative Site
• Russian Federation
  • Moscow, Russian Federation, 121552
    • Novartis Investigative Site
  • Moscow, Russian Federation, 129090
    • Novartis Investigative Site
• United States
  • Alabama
    • Muscle Shoals, Alabama, United States, 35662
      • Novartis Investigative Site
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Novartis Investigative Site
  • California
    • Encinitas, California, United States, 92024-1332
      • Novartis Investigative Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80906
      • Novartis Investigative Site
  • Florida
    • Brandon, Florida, United States, 33511
      • Novartis Investigative Site
    • Miami, Florida, United States, 33156
      • Novartis Investigative Site
    • Ocala, Florida, United States, 34471
      • Novartis Investigative Site
    • Orange City, Florida, United States, 32763
      • Novartis Investigative Site
    • Orlando, Florida, United States, 32806
      • Novartis Investigative Site
    • Port Orange, Florida, United States, 32127
      • Novartis Investigative Site
    • Saint Petersburg, Florida, United States, 33709
      • Novartis Investigative Site
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • Novartis Investigative Site
  • Maryland
    • Oxon Hill, Maryland, United States, 20745
      • Novartis Investigative Site
  • Montana
    • Butte, Montana, United States, 59701
      • Novartis Investigative Site
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • Novartis Investigative Site
    • Salisbury, North Carolina, United States, 28144
      • Novartis Investigative Site
  • Ohio
    • Lyndhurst, Ohio, United States, 44124
      • Novartis Investigative Site
    • Marion, Ohio, United States, 43302
      • Novartis Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Novartis Investigative Site
    • Oklahoma City, Oklahoma, United States, 73103
      • Novartis Investigative Site
    • Oklahoma City, Oklahoma, United States, 73135
      • Novartis Investigative Site
    • Tulsa, Oklahoma, United States, 74136
      • Novartis Investigative Site
  • Oregon
    • Eugene, Oregon, United States, 97404
      • Novartis Investigative Site
  • Pennsylvania
    • Lansdale, Pennsylvania, United States, 19446
      • Novartis Investigative Site
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Novartis Investigative Site
  • Texas
    • Boerne, Texas, United States, 78006
      • Novartis Investigative Site
    • Corpus Christi, Texas, United States, 78404
      • Novartis Investigative Site
    • Houston, Texas, United States, 77074
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female subjects ages >18 years of age, inclusive.
• History of plasma TG concentration ≥890 mg/dl (10 mmol/L) or history of lactescent plasma in the fasting state.
• Fasting TG ≥ 750 mg/dL (8.5 mmol/L) at day -7 or repeat of day -7 one week later for those failing to qualify initially and thought likely to qualify on repeat examination prior to randomization.

Exclusion Criteria:

• Treatment with Omega-3 fatty acids or niacin or fibrates within 8 weeks of screening.
• Patients with confirmed Familial Chylomicronemia Syndrome (FCS) with hyperlipoproteinemia (HLP) Type-I diagnosis or known to be homozygotes or compound heterozygotes for mutations in HLP Type I-causing genes (such as LPL, apoCII, CPIHBP1, or LMF1) prior to screening.
• Pancreatitis within 3 months prior to screening.
• Uncontrolled type 2 diabetes (T2DM) (as defined by an HbA1c value of ≥8.0% at screening)
• BMI > 40 or history of bariatric surgery.
• Nephrotic syndrome, Type 1 diabetes, HIV, HCV or HBV positive.
• Estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73m2

Other protocol defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LCQ908 1; LCQ908 (Diacylglycerol acyltransferase inhibitor)once daily for 12 weeks	Drug: LCQ908; Drug: Placebo of LCQ908; Matching placebo of LCQ908; Drug: Placebo of fenofibrate; Matching placebo of fenofibrate; Drug: Placebo of fish oil; Matching placebo of fish oil capsule
Experimental: LCQ908 2; LCQ908 once daily for 12 weeks	Drug: LCQ908; Drug: Placebo of LCQ908; Matching placebo of LCQ908; Drug: Placebo of fenofibrate; Matching placebo of fenofibrate; Drug: Placebo of fish oil; Matching placebo of fish oil capsule
Experimental: LCQ908 3; LCQ908 once daily for 12 weeks	Drug: LCQ908; Drug: Placebo of LCQ908; Matching placebo of LCQ908; Drug: Placebo of fenofibrate; Matching placebo of fenofibrate; Drug: Placebo of fish oil; Matching placebo of fish oil capsule
Active Comparator: Fenofibrate; Intervention Type: Drug Intervention Name: Fenofibrate	Drug: LCQ908; Drug: Placebo of LCQ908; Matching placebo of LCQ908; Drug: Placebo of fish oil; Matching placebo of fish oil capsule; Drug: Fenofibrate; Fenofibrate once daily 12 weeks
Active Comparator: Fish Oil; Fish oil once daily for 12 weeks	Drug: LCQ908; Drug: Placebo of LCQ908; Matching placebo of LCQ908; Drug: Placebo of fenofibrate; Matching placebo of fenofibrate; Drug: Fish Oil; Fish Oil once daily for 12 weeks; Other Names: Lovaza®
Placebo Comparator: Arm Label: Placebo; Intervention Type: other Intervention Name: other	Drug: Placebo of LCQ908; Matching placebo of LCQ908; Drug: Placebo of fenofibrate; Matching placebo of fenofibrate; Drug: Placebo of fish oil; Matching placebo of fish oil capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in triglycerides (TG) relative to placebo at 6 weeks	The dose response signal of 3 dose regiments of LCQ908 in patients at risk for non-FCS chylomicronemia as was measured by change from baseline in triglycerides (TG) relative to placebo at 6 weeks.	Baseline, 6 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in triglycerides after adding LCQ908 to background therapy of fenofibrate or Fish Oil at 12 weeks	Baseline, 12 weeks
Changes from baseline in triglycerides after treatment with LCQ908 monotherapy relative to fenofibrate or fish oil at 6 weeks	Baseline, 6 weeks
Change from baseline in triglycerides after treatment with LCQ908 monotherapy relative to placebo at 12 weeks	Baseline, 12 weeks
Number of patients in LCQ908 monotherapy with adverse events , serious adverse events and death	12 weeks
changefrom baseline in lipids and lipoprotein profiles	Baseline, 6 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CLCQ908C2201 from the Novartis Clinical Trials website

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: May 7, 2012
• First Submitted That Met QC Criteria: May 8, 2012
• First Posted (Estimate): May 9, 2012

Study Record Updates

• Last Update Posted (Actual): December 17, 2020
• Last Update Submitted That Met QC Criteria: December 11, 2020
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: hypertriglyceridemia; Non familial Chylocmicronemia Syndrome (non-FCS)
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypertriglyceridemia; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Fenofibrate
• Other Study ID Numbers: CLCQ908C2201; 2012-000872-40 (EudraCT Number)