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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01514461
First received: December 21, 2011
Last updated: July 3, 2014
Last verified: July 2014
  Purpose

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).


Condition Intervention Phase
Familial Chylomicronemia Syndrome (FCS)
Drug: LCQ908
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo Controlled Study to Assess Efficacy, Safety and Tolerability of LCQ908 in Subjects With Familial Chylomicronemia Syndrome

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percent change in fasting triglycerides from Baseline to 12 weeks [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Proportion of patients with Familial Chylomicronemia Syndrome (FCS) responding to investigational treatment [ Time Frame: 12 weeks, 24 weeks, 52 weeks ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
  • Pharmacokinetics of LCQ908 - Trough Concentration (Cmin) [ Time Frame: At weeks 0, 4, 8, 12, 16, 20, 24, 36, and 52 after dosing ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 45
Study Start Date: July 2012
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LCQ908 20 mg

In period II (0-12 weeks) double-blind treatment: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40mg tablet, once daily. No dose titration allowed.

In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen will follow. Following decision to down titrate: one LCQ908 10 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily.

A low fat diet will be followed and recorded in patient diary.

Drug: LCQ908
LCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg
Drug: Placebo
LCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg
Other Name: LCQ908
Experimental: LCQ908 40 mg

In period II (0-12 weeks) double-blind treatment: one LCQ908 40 mg active tablet + one LCQ908 placebo matching to 20mg tablet, once daily. No dose titration allowed.

In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen will follow. Following decision to down titrate: one LCQ908 20 mg active tablet + one LCQ908 placebo matching to 40 mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily.

A low fat diet will be followed and recorded in patient diary.

Drug: LCQ908
LCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg
Drug: Placebo
LCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg
Other Name: LCQ908
Placebo Comparator: Placebo

In period II (0-12 weeks) double-blind treatment: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet, once daily.

In period III (12-52 weeks) double blind treatment: Without down titration, the period II dosing regimen will follow. Following decision to down titrate: one LCQ908 placebo matching to 40mg tablet + one LCQ908 placebo matching to 20mg tablet + one LCQ908 placebo matching to 10mg tablets, once daily.

A low fat diet will be followed and recorded in patient diary.

Drug: Placebo
LCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg
Other Name: LCQ908

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent must be obtained before any assessment is performed for Period I.
  • Male and female subjects ages at least 18 years of age
  • Fasting TG ≥ 8.4 mmol/L (750 mg/dL) at Screening
  • An established diagnosis of Familial Chylomicronemia Syndrome (HLP Type I) confirmed through ultracentrifugation or by documented medical history of a fasting TG ≥ 8.4 mmol/L (750 mg/dL) and by documentation of any of the following at Screening or during the Screening Period:

    • Confirmed homozygote or compound heterozygote for known loss-of-function mutations in Type I-causing genes (such as LPL, apoCII, GPIHBP1, or LMF1)
    • Post heparin plasma LPL activity of ≤ 20% of normal
    • Confirmed presence of LPL inactivating antibodies
  • History of pancreatitis.

Exclusion Criteria:

  • Subjects with type 1 diabetes mellitus or type 2 diabetes mellitus if HbA1C is ≥ 8.5%.
  • Although a history of pancreatitis is required, this must be inactive for at least 1 week prior to the Screening Visit.
  • Treatment with fish oil preparations within 4 weeks prior to randomization.
  • Treatment with bile acid binding resins (i.e., colesevelam, etc) within 4 weeks prior to randomization.
  • Treatment with fibrates within 8 weeks prior to randomization.
  • Glybera [alipogene tiparvovec (AAV1-LPLS447X )] gene therapy exposure within the two years prior to screening
  • History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 1 year, regardless of whether there is evidence of local recurrence or metastases.
  • Any surgical or medical conditions, acute or unstable chronic disease which may, based on the investigator's opinion, jeopardize the patient in case of participation in the study or might significantly alter the absorption, distribution, metabolism or excretion of the study drug. History of drug or alcohol abuse within the 12 months prior to randomization or evidence of such abuse at screening. Evidence of liver disease or liver injury as indicated by abnormal liver function tests such as AST and ALT, or serum bilirubin. The investigator should be guided by the following criteria:
  • Use of other investigational drugs at the time of screening, or within 30 days or 5 half-lives of enrollment, whichever is longer.
  • eGFR <45 ml/min/1.73m2 or history of chronic renal disease
  • Participation in any clinical investigation within four (4) weeks prior to initial dosing or longer if required by local regulations, or any other limitation of participation based on local regulations.
  • History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive HCG laboratory test.
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 100 days after discontinuation of investigational study drug.

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01514461

Locations
United States, Washington
Novartis Investigative Site
Seatlle, Washington, United States, 98104
Canada, Quebec
Novartis Investigative Site
Chicoutimi, Quebec, Canada, G7H 7P2
Novartis Investigative Site
Ste-Foy, Quebec, Canada, G1V4M6
Canada
Novartis Investigative Site
Ouest-Montreal, Canada, H2W1R7
France
Novartis Investigative Site
Bron, France, 69677
Novartis Investigative Site
Nantes, France, 44093
Novartis Investigative Site
Paris Cedex 13, France, 75651
Germany
Novartis Investigative Site
Hamburg, Germany, 20246
Novartis Investigative Site
Köln, Germany, 50924
Netherlands
Novartis Investigative Site
Meibergdreef 9, Netherlands, 1105 AZ
South Africa
Novartis Investigative Site
Cape Town, South Africa, 7925
Spain
Novartis Investigative Site
Malaga, Andalucia, Spain, 29010
Novartis Investigative Site
Sevilla, Andalucia, Spain, 41013
United Kingdom
Novartis Investigative Site
Manchester, United Kingdom, M13 9NT
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01514461     History of Changes
Other Study ID Numbers: CLCQ908B2302, 2011-005535-68
Study First Received: December 21, 2011
Last Updated: July 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Hyperlipoproteinemia (HLP Type I)
Fasting Triglycerides

Additional relevant MeSH terms:
Hyperlipoproteinemia Type I
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on July 28, 2014