Clinical Trial: A Randomized, Double-blind, Placebo Controlled Study to Assess Efficacy, Safety and Tolerability of LCQ908 in Subjects With Familial Chylomicronemia Syndrome

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized, Double-blind, Placebo Controlled Study to Assess Efficacy, Safety and Tolerability of LCQ908 in Subjects With Familial Chylomicronemia Syndrome

Brief Summary: The purpose of this study is to determine whether LCQ908 is effective and safe in lowering triglycerides in subjects with Familial Chylomicronemia Syndrome (FCS) (Hyperlipoproteinemia [HLP] type I). Data from this study will be used to support a registration submission of LCQ908 20 mg and 40 mg as treatment of chylomicronemia in subjects with FCS (HLP Type 1).

Detailed Summary:
Sponsor: Novartis Pharmaceuticals

Current Primary Outcome: Percent Change in Fasting Triglycerides From Baseline to 12 Weeks [ Time Frame: Baseline to 12 weeks ]

Blood samples were collected for a fasting lipid panel, including triglycerides. If the 12-week value was missing, the measurement value at 12 weeks or the last available post-baseline measurement value during the double-blind treatment period was analyzed. Baseline is defined as the average of fasting triglyceride values taken at day -3 and day 1. Adjusted geometric means are calculated by back-transforming the adjusted means from the model and expressing as a percentage change from baseline.


Original Primary Outcome: Percent Change in Fasting Triglycerides From Baseline to 12 Weeks [ Time Frame: Baseline to 12 weeks ]

Blood samples will be collected for a fasting lipid panel, including triglycerides. The primary efficacy variable is defined as percent change in fasting triglycerides from baseline to the end of the double-blind treatment period (the measurement value at 12 weeks or the last available post-baseline measurement value during the double-blind treatment period, if the 12-week value is missing). Baseline is defined as the average of fasting triglyceride values taken at day -3 and day 1.


Current Secondary Outcome:

  • Percentage of Patients Responding to Investigational Treatment by Achieving Fasting Triglycerides (TG) of at Least 40% From Baseline or Final Fasting TG < 8.4 mmol/L (750 mg/dL) [ Time Frame: Baseline, 12 weeks, 24 weeks, 52 weeks ]
    Percentage calculated as (m/n)*100 where m = number of patients who respond; n = the number of patients with non-missing fasting triglyceride.
  • Percentage of Patients Responding to Investigational Treatment by Achieving Final Fasting Triglycerides < 8.4 mmol/L (750 mg/dL) [ Time Frame: 12 weeks, 24 weeks, 52 weeks ]
    Percentage calculated as (m/n)*100 where m = number of patients who respond; n = the number of patients with non-missing fasting triglyceride.
  • Percentage of Patients Responding to Investigational Treatment by Achieving Fasting Triglycerides (TG) of at Least 40% From Baseline [ Time Frame: Baseline, 12 weeks, 24 weeks, 52 weeks ]
    Percentage calculated as (m/n)*100 where m = number of patients who respond; n = the number of patients with non-missing fasting triglyceride.
  • Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds [ Time Frame: 12 weeks, 24 weeks, 52 weeks ]
    Percentage of patients reaching target values of <1000 mg/dL or target values of < 2000 mg/dL for fasting triglycerides is reported. Pecentage calculated as (m/n)*100; where 'm' The number of patients who reach target values for fasting triglyceride, 'n' the number of patients with non-missing fasting triglyceride.
  • Percent Change From Baseline in Fasting Triglycerides [ Time Frame: Baseline, 24 weeks, 52 weeks ]
  • Percent Change From Baseline for Postprandial Triglycerides Following the Standardized Meal Tolerance Test at Week 12 [ Time Frame: 0-24 hours at Baseline, Week 12 ]
    Post prandial peak triglycerides - maximum triglyceride value over 0-24 hours Post prandial triglycerides AUC0-24 - area under the time curve for triglycerides over 0-24 Adjusted geometric means are calculated by back-transforming the adjusted means from the model and expressed as a percentage change from baseline. hours
  • Pharmacokinetics of LCQ908 - Trough Concentration (Cmin) and Observed Maximum Blood Concentration (Cmax) [ Time Frame: 0, 1, 2, 3, 4, 6, and 24 hours at Week 12 ]
    Lowest observed blood concentration (Cmin) and observed maximum blood concentration (Cmax) following drug administration derived from non-compartmental analysis using scheduled sampling time for the whole dataset.
  • Pharmacokinetics of LCQ908- Area Under the Plasma Concentration Time Curve AUC (0-24hour) [ Time Frame: 0, 1, 2, 3, 4, 6, and 24 hours at Week 12 ]
    The area under the concentration-time curve from time zero to 24 hours after drug administration was calculated by using linear trapezoidal rule.
  • Pharmacokinetics of LCQ908- Time to Reach Maximum Concentration Following Drug Administration Tmax (Hours) [ Time Frame: 0, 1, 2, 3, 4, 6, and 24 hours at Week 12 ]
  • Pharmacokinetics of LCQ908- Average Observed Blood Concentration (Cavg) [ Time Frame: 0, 1, 2, 3, 4, 6, and 24 hours at Week 12 ]
    Average observed blood concentration measured by (AUC0-24)/24.
  • Number of Patients Reported With Any Adverse Event, Serious Adverse Event and Death [ Time Frame: 52 weeks ]


Original Secondary Outcome:

  • Proportion of patients with Familial Chylomicronemia Syndrome (FCS) responding to investigational treatment [ Time Frame: 12 weeks, 24 weeks, 52 weeks ]

    Response to investigational treatment at a post-baseline visit will be characterized in three different ways:

    • achieving fasting triglycerides of at least 40% from baseline or final fasting triglycerides < 8.4 mmol/L (750 mg/dL)
    • achieving fasting triglycerides of at least 40% from baseline
    • achieving final fasting triglycerides < 8.4 mmol/L (750 mg/dL)
  • Proportion of subjects achieving fasting triglycerides (TG) target thresholds including TG < 1000 mg/dL (11.4 mmol/L) or < 2000 mg/dL (22.8 mmol/L) [ Time Frame: 12 weeks, 24 weeks, 52 weeks ]
  • Pharmacokinetics of LCQ908 - Trough Concentration (Cmin) [ Time Frame: At weeks 0, 4, 8, 12, 16, 20, 24, 36, and 52 after dosing ]
  • Pharmacokinetics of LCQ908- Area under the plasma concentration time curve AUC (0-8hour) [ Time Frame: At weeks 0, 4, 8, 12, 16, 20, 24, 36, and 52 after dosing ]


Information By: Novartis

Dates:
Date Received: December 21, 2011
Date Started: July 2012
Date Completion:
Last Updated: May 15, 2015
Last Verified: May 2015