Efficacy of LCQ908 on Cardiovascular Risk

This study has been terminated.
(The study was terminated based on interim analysis. See detailed description.)
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01474434
First received: November 9, 2011
Last updated: March 16, 2016
Last verified: March 2016
  Purpose
This is a study designed to evaluate the potential for the pradigastat (LCQ908) to impact cardiovascular risk.

Condition Intervention Phase
Coronary Artery Disease
Hypertriglyceridemia
Drug: pradigastat (LCQ908)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo Controlled Study to Assess the Efficacy of LCQ908 on Cardiovascular Risk

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change From Baseline in Myocardial Perfusion Reserve Index (MPRi) Overall Mean (Part A, Cohort 1) [ Time Frame: Baseline, and on day 5 of each of the two treatment periods ] [ Designated as safety issue: No ]
    MPRi (myocardial perfusion reserve index) is a measure of coronary microvascular function. Myocardial perfusion scans using 0.05 mmol/kg of gadolinium contrast were acquired at rest and under stress (pharmacological stress induced with adenosine 140 μg/kg/min for three minutes). An independent central reader performed the cardiac image analysis of all time points including the calculation of the myocardial perfusion reserve index from the ratio of the global stress myocardial blood flow divided by the resting blood flow values. Higher/increased index indicates improved flow/better outcome. This primary endpoint was only for Part A, Cohort 1 patients.

  • Change From Baseline in Total Exercise Duration (Part A, Cohort 1) [ Time Frame: Baseline and on day 5 of each of the two treatment periods ] [ Designated as safety issue: No ]
    Total exercise duration was the elapsed time between the start of exercise and termination of exercise for severe angina, dyspnea or extreme fatigue. This primary endpoint was only for Part A, Cohort 1 patients.

  • Time to Onset of Angina (Part A, Cohort 1) [ Time Frame: Baseline and on day 5 of each of the two treatment periods ] [ Designated as safety issue: No ]
    Time to onset of angina was defined as the elapsed time between the start of exercise and the onset of anginal chest pain as reported by the patient and recorded by the performing investigator.

  • Time to Onset of Exercise-induced Ischemia(Part A, Cohort 1) [ Time Frame: Baseline and on day 5 of each of the two treatment periods ] [ Designated as safety issue: No ]
    Exercise-induced ischemia was defined as the new development of horizontal or down-sloping ST-segment depression (≥ 1mm at 60 milliseconds after the J point) versus baseline tracings.

  • Aortic Plaque Inflammation (Part B) [ Time Frame: Baseline and on treatment day 85 +/- 3 days ] [ Designated as safety issue: No ]
    This endpoint was palnned for analysis on Part B patients which was never started becasue study got terminated on Part A interim analysis.


Secondary Outcome Measures:
  • Number of Participants With Adverse Events (Part A, Cohort 1) [ Time Frame: approximately 40 days ] [ Designated as safety issue: No ]
  • Number of Participants With Adverse Events (Part A, Cohort 2) [ Time Frame: approximately 40 days ] [ Designated as safety issue: No ]
  • Postprandial Triglycerides (Part A, Cohort 1) [ Time Frame: 0 hour (before breakfast), 2 and 4 hours post high-fat breakfast on day 5 ] [ Designated as safety issue: No ]
    For both each treatment period, postprandial triglycerides were measured on Day 5 i.e. on 0 hour(before breakfast), two hours and four hours post high-fat breakfast. Results are from an ANCOVA model on change from baseline in the log domain with log(baseline), treatment, sequence and period as fixed effects. Baseline is the Day -1 value within period. The data reported is ratio of geometric mean between post-treatment and baseline data.

  • Postprandial Triglycerides (Part A, Cohort 2) [ Time Frame: 0 hour (before breakfast), 2 and 4 hours post high-fat breakfast on day 5 ] [ Designated as safety issue: No ]
    For both each treatment period, postprandial triglycerides were measured on Day 5 i.e. on 0 hour (before breakfast), two hours and four hours post high-fat breakfast. Results are from an ANCOVA model on change from baseline in the log domain with log(baseline), treatment, sequence and period as fixed effects. Baseline is the Day -1 value within period. The data reported is ratio of geometric mean between post-treatment and baseline data.

  • Pharmacokinetics of Pradigastat (LCQ908): Plasma Concentration (Part A) [ Time Frame: Part A: Day 4 and day 5 of each treatment period ] [ Designated as safety issue: No ]
  • Other Related Lipid Parameters (Part A) [ Time Frame: Baseline, day 4 and day 5 of each treatment period ] [ Designated as safety issue: No ]
  • Interleukin-6 (IL-6) Level (Part A) [ Time Frame: Baseline, day 4 and day 5, of each treatment period ] [ Designated as safety issue: No ]
  • C-reactive Protein (CRP) Level (Part A) [ Time Frame: Baseline, day 4 and day 5, of each treatment period ] [ Designated as safety issue: No ]
  • Adiponectin Level ( Part B) [ Time Frame: Part B; Baseline, day 15, day 43 and day 85 ] [ Designated as safety issue: No ]

Enrollment: 41
Study Start Date: December 2011
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pradigastat (LCQ908) followed by placebo
Pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by pradigastat 20 mg (2 x 10-mg tablets) daily for two days followed by a 30-day washout period in between followed by 5-day placebo treatment
Drug: pradigastat (LCQ908)
pradigastat tablets were supplied to the investigators at dose strengths of 10 mg and 20 mg as individual patient packs.
Other Name: Pradigastat
Drug: Placebo
matching placebo tablets
Experimental: Placebo followed by pradigastat (LCQ908)
Placebo (5-day treatment period) followed by a 30-day washout period followed by pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by p20 mg (2 x 10-mg tablets) daily for two days
Drug: pradigastat (LCQ908)
pradigastat tablets were supplied to the investigators at dose strengths of 10 mg and 20 mg as individual patient packs.
Other Name: Pradigastat
Drug: Placebo
matching placebo tablets

Detailed Description:

This study had 2 parts. Part A was a multicenter, double-blind, randomized, placebo-controlled, non-confirmatory crossover study assessing response to a high-fat meal challenge in the setting of pradigastat versus placebo. Part A had 2 cohorts i.e. Cohort 1 patients with stable coronary artery disease and hypertriglyceridemia and Cohort 2 patients with asymptomatic non-obstructive coronary artery disease or elevated coronary heart disease risk and hypertriglyceridemia.

Part B was a double blinded phase designed to assess response to three months of chronic treatment with pradigastat versus placebo on a normal diet.

The trial was terminated after the interim analysis of Part A, Cohort 1. The interim analysis results indicated that the high-fat meal challenge did not induce any impairment on either myocardial perfusion reserve index (MPRi) or exercise treadmill performance. Part B was never started.

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • History of coronary artery disease
  • Elevated triglycerides
  • On medication to help lower cholesterol

Exclusion Criteria:

  • Poorly controlled diabetic patients and/or change in diabetic medication within 12 weeks of screening
  • History of myocardial infarction (heart attack) within 6 months of screening
  • History of a procedure to open a blocked coronary artery within 12 months of enrollment
  • History of Coronary Artery Bypass Graft (CABG) surgery
  • History of congestive heart failure
  • History of significant heart valve disease
  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: NCT01474434

Locations
United States, California
Novartis Investigative Site
Pasadena, California, United States, 91105
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01474434     History of Changes
Other Study ID Numbers: CLCQ908A2213 
Study First Received: November 9, 2011
Results First Received: June 4, 2015
Last Updated: March 16, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
coronary artery disease,
LCQ908,
hyperlipidemia,
hypertriglyceridemia,
pradigastat

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Hypertriglyceridemia
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on July 27, 2016