a randomized, double-blind, placebo controlled study to assess efficacy, safety and tolerability of lcq908 in subjects with familial chylomicronemia syndrome

Conditions: Familial Chylomicronemia Syndrome (FCS)

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).


Eligibility criteria:
key inclusion criteria: 1. written informed consent given before any assessment was performed for period i. 2. male and female patients ages at least 18 years of age. 3. fasting triglyceride ≥ 8.4 mmol/l (750 mg/dl) at screening. 4. an established diagnosis of fcs (hlp type i) confirmed through ultracentrifugation or by documented medical history of a fasting triglyceride ≥ 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, apo c ii, gpihbp1, or lmf1) * post heparin plasma lpl activity of ≤ 20% of normal * confirmed presence of lpl inactivating antibodies 5. history of pancreatitis. key exclusion criteria: 1. current pancreatitis, pancreatitis was required to be inactive for at least 1 week prior to the screening visit. 2. treatment with fish oil preparations within 4 weeks prior to randomization. 3. treatment with bile acid binding resins (i.e., colesevelam, etc.) within 4 weeks prior to randomization. 4. treatment with fibrates within 4 weeks prior to randomization. 5. glybera \[alipogene tiparvovec (aav1-lpls447x)\] gene therapy exposure within the two years prior to screening. 6. 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. 7. 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. 8. history of drug or alcohol abuse within the 12 months prior to randomization or evidence of such abuse at screening. 9. evidence of liver disease or liver injury as indicated by abnormal liver function tests such as aspartate aminotransferase (ast) and alanine aminotransferase (alt), or serum bilirubin. 10. estimated glomerular filtration rate (egfr) \<30ml/min/1.73m2 or history of chronic renal disease. 11. 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. 12. history of hypersensitivity to any of the study drugs or to drugs of similar chemical classes. 13. 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. 14. 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.

Keywords: hyperlipoproteinemia (hlp type i) fasting triglycerides