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

November 9, 2011
March 16, 2016
December 2011
June 2014   (final data collection date for primary outcome measure)
  • 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.
  • Myocardial perfusion [ Time Frame: Up to 5 days during each of 2 treatment periods ] [ Designated as safety issue: No ]
    Changes in blood flow to the myocardium (heart muscle) will be determined before and after treatment
  • Inflammation and myocardial perfusion [ Time Frame: Up to Day 85 days during treatment period ] [ Designated as safety issue: No ]
    Changes in inflammation as well as changes in blood flow to the myocardium (heart muscle) will be determined before and after treatment
Complete list of historical versions of study NCT01474434 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Lipids [ Time Frame: Part A: Up to 5 days during each of two treatment periods; Part B: Up to 85 days during the treatment period ] [ Designated as safety issue: No ]
    The levels of lipids and related particles in the blood will be measured
  • Biological Markers [ Time Frame: Part A: Up to 5 days during each of two treatment periods; Part B: Up to 85 days during treatment period ] [ Designated as safety issue: No ]
    The level of biological markers of physiologic process in the blood will be measured
  • Safety and Tolerability [ Time Frame: Part A:Up to 5 days during each of two treatment periods; Part B: Up to 85 days during treatment period ] [ Designated as safety issue: Yes ]
    Safety and tolerability including percentage of adverse events, laboratory analysis, impact on vital signs (blood pressure and pulse rate) and impact on ECGs will be assessed.
  • Levels of the study drug in the blood [ Time Frame: Part A: Up to 5 days during each of two treatment periods - daily; Part B: Up to 85 days during treatment period ] [ Designated as safety issue: No ]
    The level of the study drug in the blood will be measured at set points after the drug has been taken.
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Efficacy of LCQ908 on Cardiovascular Risk
A Randomized, Double-blind, Placebo Controlled Study to Assess the Efficacy of LCQ908 on Cardiovascular Risk
This is a study designed to evaluate the potential for the pradigastat (LCQ908) to impact cardiovascular risk.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Coronary Artery Disease
  • Hypertriglyceridemia
  • 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: 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
    Interventions:
    • Drug: pradigastat (LCQ908)
    • Drug: Placebo
  • 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
    Interventions:
    • Drug: pradigastat (LCQ908)
    • Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
41
June 2014
June 2014   (final data collection date for primary outcome measure)

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
Both
40 Years to 80 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01474434
CLCQ908A2213
Not Provided
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Novartis Pharmaceuticals
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
March 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP