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

NCT01514461 | Completed Phase 3 Results

• 2 other identifiers: CLCQ908B23022011-005535-68
• Study Type: interventional
• Target: 45
• Locations: 8 countries
• Sites: 14

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).

Conditions

Familial Chylomicronemia Syndrome (FCS)

Keywords

Hyperlipoproteinemia (HLP Type I); Fasting Triglycerides

Outcome Measures

Primary Outcomes (1)

• Percent Change in Fasting Triglycerides From 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.

  Baseline to 12 weeks

Secondary Outcomes (11)

• 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)

  Baseline, 12 weeks, 24 weeks, 52 weeks

• Percentage of Patients Responding to Investigational Treatment by Achieving Final Fasting Triglycerides < 8.4 mmol/L (750 mg/dL)

  12 weeks, 24 weeks, 52 weeks

• Percentage of Patients Responding to Investigational Treatment by Achieving Fasting Triglycerides (TG) of at Least 40% From Baseline

  Baseline, 12 weeks, 24 weeks, 52 weeks

• Percentage of Patients Achieving Fasting Triglycerides (TG) Target Thresholds

  12 weeks, 24 weeks, 52 weeks

• Percent Change From Baseline in Fasting Triglycerides

  Baseline, 24 weeks, 52 weeks

Study Arms (3)

LCQ908 20 mg

EXPERIMENTAL

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; Drug: Placebo

LCQ908 40 mg

EXPERIMENTAL

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; Drug: Placebo

Placebo

PLACEBO COMPARATOR

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

Interventions

LCQ908 DRUG

LCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg

LCQ908 20 mg; LCQ908 40 mg

Placebo DRUG

LCQ908 10 mg, LCQ908 20 mg, LCQ908 40 mg

Also known as: LCQ908

LCQ908 20 mg; LCQ908 40 mg; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent given before any assessment was performed for Period I.
• Male and female patients ages at least 18 years of age.
• Fasting triglyceride ≥ 8.4 mmol/L (750 mg/dL) at Screening.
• 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
• History of pancreatitis.

You may not qualify if:

• Current pancreatitis, pancreatitis was required to 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 4 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 5 years, 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 aspartate aminotransferase (AST) and alanine aminotransferase (ALT), or serum bilirubin.
• Estimated glomerular filtration rate (eGFR) \<30mL/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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (14)

Novartis Investigative Site

Seatlle, Washington, 98104, United States

Location

Novartis Investigative Site

Chicoutimi, Quebec, G7H 7P2, Canada

Location

Novartis Investigative Site

Ste-Foy, Quebec, G1V4M6, Canada

Location

Novartis Investigative Site

Ouest-Montreal, H2W1R7, Canada

Location

Novartis Investigative Site

Bron, 69677, France

Location

Novartis Investigative Site

Nantes, 44093, France

Location

Novartis Investigative Site

Paris, 75651, France

Location

Novartis Investigative Site

Cologne, 50937, Germany

Location

Novartis Investigative Site

Hamburg, 20246, Germany

Location

Novartis Investigative Site

Meibergdreef 9, 1105 AZ, Netherlands

Location

Novartis Investigative Site

Cape Town, 7925, South Africa

Location

Novartis Investigative Site

Málaga, Andalusia, 29010, Spain

Location

Novartis Investigative Site

Seville, Andalusia, 41013, Spain

Location

Novartis Investigative Site

Manchester, M13 9NT, United Kingdom

Location

MeSH Terms

Conditions

Familial hyperchylomicronemia syndrome; Hyperlipoproteinemias

Interventions

pradigastat

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2011
• First Posted: January 23, 2012
• Study Start: July 1, 2012
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: June 3, 2015
• Results First Posted: June 3, 2015

Record last verified: 2015-05

Locations

GB (1); CA (3); DE (2); ES (2); US (1); NL (1); FR (3); ZA (1)