Efficacy of LCQ908 on Cardiovascular Risk

NCT01474434 | Terminated Phase 2 Results

• 1 other identifier: CLCQ908A2213
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study designed to evaluate the potential for the pradigastat (LCQ908) to impact cardiovascular risk.

Conditions

Coronary Artery Disease; Hypertriglyceridemia

Keywords

coronary artery disease,; LCQ908,; hyperlipidemia,; hypertriglyceridemia,; pradigastat

Outcome Measures

Primary Outcomes (5)

• Change From Baseline in Myocardial Perfusion Reserve Index (MPRi) Overall Mean (Part A, Cohort 1)

  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.

  Baseline, and on day 5 of each of the two treatment periods

• Change From Baseline in Total Exercise Duration (Part A, Cohort 1)

  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.

  Baseline and on day 5 of each of the two treatment periods

• Time to Onset of Angina (Part A, Cohort 1)

  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.

  Baseline and on day 5 of each of the two treatment periods

• Time to Onset of Exercise-induced Ischemia(Part A, Cohort 1)

  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.

  Baseline and on day 5 of each of the two treatment periods

• Aortic Plaque Inflammation (Part B)

  This endpoint was palnned for analysis on Part B patients which was never started becasue study got terminated on Part A interim analysis.

  Baseline and on treatment day 85 +/- 3 days

Secondary Outcomes (9)

• Number of Participants With Adverse Events (Part A, Cohort 1)

  approximately 40 days

• Number of Participants With Adverse Events (Part A, Cohort 2)

  approximately 40 days

• Postprandial Triglycerides (Part A, Cohort 1)

  0 hour (before breakfast), 2 and 4 hours post high-fat breakfast on day 5

• Postprandial Triglycerides (Part A, Cohort 2)

  0 hour (before breakfast), 2 and 4 hours post high-fat breakfast on day 5

• Pharmacokinetics of Pradigastat (LCQ908): Plasma Concentration (Part A)

  Part A: Day 4 and day 5 of each treatment period

Study Arms (2)

Pradigastat (LCQ908) followed by placebo

EXPERIMENTAL

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); Drug: Placebo

Placebo followed by pradigastat (LCQ908)

EXPERIMENTAL

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); Drug: Placebo

Interventions

pradigastat (LCQ908) DRUG

pradigastat tablets were supplied to the investigators at dose strengths of 10 mg and 20 mg as individual patient packs.

Also known as: Pradigastat

Placebo followed by pradigastat (LCQ908); Pradigastat (LCQ908) followed by placebo

Placebo DRUG

matching placebo tablets

Placebo followed by pradigastat (LCQ908); Pradigastat (LCQ908) followed by placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Pasadena, California, 91105, United States

Location

MeSH Terms

Conditions

Coronary Artery Disease; Hypertriglyceridemia; Hyperlipidemias

Interventions

pradigastat

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

The study was terminated based on the interim analysis on Part A, Cohort 1 after patients completed Part A. Part B was not conducted. Not all the planned assessments were completed due to the termination

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 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2011
• First Posted: November 18, 2011
• Study Start: December 1, 2011
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: April 14, 2016
• Results First Posted: April 14, 2016

Record last verified: 2016-03

Locations

US (1)