A Pilot Study to Assess the Efficacy and Safety of LCQ908 Alone and in Combination With Fenofibrate or Lovaza® in Patients With Severe Hypertriglyceridemia

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01594983

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

1.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is to determine a dose response signal for LCQ908 monotherapy and to assess the efficacy and safety of adding LCQ908 to Lovaza or fenofibrate.

Condition or Disease	Intervention/Treatment	Phase
Non Familial Chylocmicronemia Syndrome (Non-FCS)	Drug: LCQ908 Drug: Fenofibrate Drug: Fish Oil Drug: Placebo of LCQ908 Drug: Placebo of fenofibrate Drug: Placebo of fish oil	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

58 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Multicenter, Randomized, Active Comparator, Placebo Controlled, Double-blind Pilot Study to Assess the Efficacy and Safety of LCQ908 Alone and in Combination With Fenofibrate or Lovaza® in Patients With Severe Hypertriglyceridemia

Study Start Date :

Jun 1, 2012

Actual Primary Completion Date :

Jul 1, 2013

Actual Study Completion Date :

Jul 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LCQ908 1 LCQ908 (Diacylglycerol acyltransferase inhibitor)once daily for 12 weeks	Drug: LCQ908 Drug: Placebo of LCQ908 Matching placebo of LCQ908 Drug: Placebo of fenofibrate Matching placebo of fenofibrate Drug: Placebo of fish oil Matching placebo of fish oil capsule
Experimental: LCQ908 2 LCQ908 once daily for 12 weeks	Drug: LCQ908 Drug: Placebo of LCQ908 Matching placebo of LCQ908 Drug: Placebo of fenofibrate Matching placebo of fenofibrate Drug: Placebo of fish oil Matching placebo of fish oil capsule
Experimental: LCQ908 3 LCQ908 once daily for 12 weeks	Drug: LCQ908 Drug: Placebo of LCQ908 Matching placebo of LCQ908 Drug: Placebo of fenofibrate Matching placebo of fenofibrate Drug: Placebo of fish oil Matching placebo of fish oil capsule
Active Comparator: Fenofibrate Intervention Type: Drug Intervention Name: Fenofibrate	Drug: LCQ908 Drug: Fenofibrate Fenofibrate once daily 12 weeks Drug: Placebo of LCQ908 Matching placebo of LCQ908 Drug: Placebo of fish oil Matching placebo of fish oil capsule
Active Comparator: Fish Oil Fish oil once daily for 12 weeks	Drug: LCQ908 Drug: Fish Oil Fish Oil once daily for 12 weeks Other Names: Lovaza® Drug: Placebo of LCQ908 Matching placebo of LCQ908 Drug: Placebo of fenofibrate Matching placebo of fenofibrate
Placebo Comparator: Arm Label: Placebo Intervention Type: other Intervention Name: other	Drug: Placebo of LCQ908 Matching placebo of LCQ908 Drug: Placebo of fenofibrate Matching placebo of fenofibrate Drug: Placebo of fish oil Matching placebo of fish oil capsule

Outcome Measures

Primary Outcome Measures

Change from baseline in triglycerides (TG) relative to placebo at 6 weeks [Baseline, 6 weeks]
The dose response signal of 3 dose regiments of LCQ908 in patients at risk for non-FCS chylomicronemia as was measured by change from baseline in triglycerides (TG) relative to placebo at 6 weeks.

Secondary Outcome Measures

Change from baseline in triglycerides after adding LCQ908 to background therapy of fenofibrate or Fish Oil at 12 weeks [Baseline, 12 weeks]
Changes from baseline in triglycerides after treatment with LCQ908 monotherapy relative to fenofibrate or fish oil at 6 weeks [Baseline, 6 weeks]
Change from baseline in triglycerides after treatment with LCQ908 monotherapy relative to placebo at 12 weeks [Baseline, 12 weeks]
Number of patients in LCQ908 monotherapy with adverse events , serious adverse events and death [12 weeks]
changefrom baseline in lipids and lipoprotein profiles [Baseline, 6 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male and female subjects ages >18 years of age, inclusive.
History of plasma TG concentration ≥890 mg/dl (10 mmol/L) or history of lactescent plasma in the fasting state.
Fasting TG ≥ 750 mg/dL (8.5 mmol/L) at day -7 or repeat of day -7 one week later for those failing to qualify initially and thought likely to qualify on repeat examination prior to randomization.

Exclusion Criteria:

Treatment with Omega-3 fatty acids or niacin or fibrates within 8 weeks of screening.
Patients with confirmed Familial Chylomicronemia Syndrome (FCS) with hyperlipoproteinemia (HLP) Type-I diagnosis or known to be homozygotes or compound heterozygotes for mutations in HLP Type I-causing genes (such as LPL, apoCII, CPIHBP1, or LMF1) prior to screening.
Pancreatitis within 3 months prior to screening.
Uncontrolled type 2 diabetes (T2DM) (as defined by an HbA1c value of ≥8.0% at screening)
BMI > 40 or history of bariatric surgery.
Nephrotic syndrome, Type 1 diabetes, HIV, HCV or HBV positive.
Estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73m2

Other protocol defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Muscle Shoals	Alabama	United States	35662
2	Novartis Investigative Site	Glendale	Arizona	United States	85306
3	Novartis Investigative Site	Encinitas	California	United States	92024-1332
4	Novartis Investigative Site	Colorado Springs	Colorado	United States	80906
5	Novartis Investigative Site	Brandon	Florida	United States	33511
6	Novartis Investigative Site	Miami	Florida	United States	33156
7	Novartis Investigative Site	Ocala	Florida	United States	34471
8	Novartis Investigative Site	Orange City	Florida	United States	32763
9	Novartis Investigative Site	Orlando	Florida	United States	32806
10	Novartis Investigative Site	Port Orange	Florida	United States	32127
11	Novartis Investigative Site	Saint Petersburg	Florida	United States	33709
12	Novartis Investigative Site	Louisville	Kentucky	United States	40213
13	Novartis Investigative Site	Oxon Hill	Maryland	United States	20745
14	Novartis Investigative Site	Butte	Montana	United States	59701
15	Novartis Investigative Site	Cary	North Carolina	United States	27518
16	Novartis Investigative Site	Salisbury	North Carolina	United States	28144
17	Novartis Investigative Site	Lyndhurst	Ohio	United States	44124
18	Novartis Investigative Site	Marion	Ohio	United States	43302
19	Novartis Investigative Site	Oklahoma City	Oklahoma	United States	73103
20	Novartis Investigative Site	Oklahoma City	Oklahoma	United States	73112
21	Novartis Investigative Site	Oklahoma City	Oklahoma	United States	73135
22	Novartis Investigative Site	Tulsa	Oklahoma	United States	74136
23	Novartis Investigative Site	Eugene	Oregon	United States	97404
24	Novartis Investigative Site	Lansdale	Pennsylvania	United States	19446
25	Novartis Investigative Site	Bristol	Tennessee	United States	37620
26	Novartis Investigative Site	Boerne	Texas	United States	78006
27	Novartis Investigative Site	Corpus Christi	Texas	United States	78404
28	Novartis Investigative Site	Houston	Texas	United States	77074
29	Novartis Investigative Site	Chicoutimi	Quebec	Canada	G7H 5H6
30	Novartis Investigative Site	Ste-Foy	Quebec	Canada	G1V4M6
31	Novartis Investigative Site	Moscow		Russian Federation	121552
32	Novartis Investigative Site	Moscow		Russian Federation	129090