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Extension to a Randomized, Double-blind, Placebo Controlled Study of LCQ908 in Subjects With Familial Chylomicronemia Syndrome.

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ClinicalTrials.gov Identifier: NCT01589237
Recruitment Status : Terminated (Interim analysis suggested that size of benefit anticipated from continued participation of patients in Part B no longer supported trial extension beyond Part A)
First Posted : May 1, 2012
Results First Posted : November 15, 2016
Last Update Posted : November 15, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This study was to determine long-term safety and tolerability, and continued efficacy in lowering triglycerides of LCQ908 in subjects with Familial Chylomicronemia Syndrome (FCS) (HLP type I).

Condition or disease Intervention/treatment Phase
Familial Chylomicronemia Syndrome (FCS) (HLP Type I) Drug: LCQ908 Phase 3

Detailed Description:

This study was an 52 weeks open label extension starting at the lowest treatment dose used in CLCQ908B2302/NCT01514461 (i.e., 10 mg) with optional up-titrations, to evaluate the overall long-term safety and tolerability of LCQ908 in patients with Familial Chylomicronemia Syndrome, who either discontinued from the CLCQ908B2302/NCT01514461 study (due to tolerability issues) or completed the CLCQ908B2302/NCT01514461 study after 52 weeks. In addition, patients who had previously completed study CLCQ908A2212/NCT01146522 were eligible to participate.

Following Protocol amendment 2, the original 52 week duration of this study (CLCQ908B2305) became Part A of LCQ908B2305 and a 78 week extension became Part B. However, following Protocol amendment 3, Part B was ended at the same time as the last patient of Part A completed 52 weeks. The reason for termination of Part B was the findings from the December 2014 interim analysis which suggested that the size of benefit that was anticipated from continued participation of patients in the 18 month extension trial (Part B) no longer supported trial extension beyond Part A.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label, 52-week, Safety and Tolerability Extension to a Randomized, Double-blind, Placebo Controlled Study of LCQ908 in Subjects With Familial Chylomicronemia Syndrome.
Study Start Date : February 2013
Actual Primary Completion Date : July 2015
Actual Study Completion Date : July 2015


Arm Intervention/treatment
Experimental: LCQ908
Patients initiated at 10 mg/day. After at least 8 weeks of treatment with a dose, optional up-titration to the next possible dose will be allowed. One down titration allowed from the highest dose attained.
Drug: LCQ908



Primary Outcome Measures :
  1. Number of Patients With Any Adverse Events, Serious Adverse Events and Death [ Time Frame: 52 weeks ]

Secondary Outcome Measures :
  1. Changes From Baseline in Triglyceride Levels up to 52 Weeks [ Time Frame: Baseline, Week 12, 24 and 52 ]
    Blood samples were collected for a fasting lipid panel, including total triglycerides. Lipid measurements were collected after a 12 hour (overnight) fast. The maintenance of effect was assessed on triglyceride levels during continued therapy with LCQ908 for up to 52 weeks. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.

  2. Changes From Baseline in Cholesterol Levels up to 52 Weeks [ Time Frame: Baseline, Week 12, 24 and 52 ]
    Blood samples were collected for a fasting lipid panel, including cholesterol level. Lipid measurements were collected after a 12 hour (overnight) fast. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.

  3. Changes From Baseline in HDL and Non HDL Cholesterol Levels up to 52 Weeks [ Time Frame: Baseline, Week 12, 24 and 52 ]
    Blood samples were collected for a fasting lipid panel, including HDL and non HDL cholesterol level. Lipid measurements were collected after a 12 hour (overnight) fast. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.

  4. Changes From Baseline in Glycerol Levels up to 52 Weeks [ Time Frame: Baseline, Week 12, 24 and 52 ]
    Blood samples were collected for a fasting lipid panel, including glycerol level. Lipid measurements were collected after a 12 hour (overnight) fast. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.

  5. Changes From Baseline in Free Fatty Acid Levels up to 52 Weeks [ Time Frame: Baseline, Week 12, 24 and 52 ]
    Blood samples were collected for a fasting lipid panel, including free fatty acid level. Lipid measurements were collected after a 12 hour (overnight) fast. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.

  6. Changes From Baseline in Apolipoprotein A1 Levels up to 52 Weeks [ Time Frame: Baseline, Week 12, 24 and 52 ]
    Fasting blood samples were collected by direct venipuncture or an indwelling cannula to evaluate the drug effect on lipoprotein biomarkers such as Apolipoprotein A1. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.

  7. Changes From Baseline in Apolipoprotein B-48 Levels up to 52 Weeks [ Time Frame: Baseline, Week 12, 24 and 52 ]
    Fasting blood samples were collected by direct venipuncture or an indwelling cannula to evaluate the drug effect on lipoprotein biomarkers such as Apolipoprotein B-48. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.

  8. Changes From Baseline in Apolipoprotein B-100 Levels up to 52 Weeks [ Time Frame: Baseline, Week 12, 24 and 52 ]
    Fasting blood samples were collected by direct venipuncture or an indwelling cannula to evaluate the drug effect on lipoprotein biomarkers such as Apolipoprotein B-100. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent must be obtained before any assessment is performed.
  2. Subjects that either discontinue prematurely or complete the CLCQ908B2302 study after 52 weeks or FCS subjects who have previously completed study CLCQ908A2212.

Exclusion Criteria:

  1. Subjects discontinued from the CLCQ908B2302 study for serious, potentially study drug related adverse events.
  2. Subjects from the CLCQ908B2302 study who have developed any other contraindication to participation (for example, renal failure)
  3. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
  4. 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.
  5. Subjects with type 1 diabetes mellitus or type 2 diabetes mellitus if HbA1C is ≥ 8.5%.
  6. Treatment with fish oil preparations within 4 weeks prior to randomization.
  7. Treatment with bile acid binding resins (i.e., colesevelam, etc) within 4 weeks prior to randomization.
  8. Treatment with fibrates within 8 weeks prior to randomization. Washout may occur following screening if required.
  9. Glybera [alipogene tiparvovec (AAV1-LPLS447X )] gene therapy exposure within the two years prior to screening.
  10. eGFR <45 ml/min/1.73m2 or history of chronic renal disease.

Other protocol defined inclusion/exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01589237


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
Nantes, France, 44093
Novartis Investigative Site
Paris Cedex 13, France, 75651
Germany
Novartis Investigative Site
Hamburg, Germany, 20246
Netherlands
Novartis Investigative Site
Meibergdreef 9, Netherlands, 1105 AZ
South Africa
Novartis Investigative Site
Cape Town, South Africa, 7925
United Kingdom
Novartis Investigative Site
Manchester, United Kingdom, M13 9NT
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01589237     History of Changes
Other Study ID Numbers: CLCQ908B2305
2012-000802-32 ( EudraCT Number )
First Posted: May 1, 2012    Key Record Dates
Results First Posted: November 15, 2016
Last Update Posted: November 15, 2016
Last Verified: September 2016

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Familial Chylomicronemia Syndrome (FCS) (HLP type I)
LCQ908

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