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
Results First Received: June 4, 2015  
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
Conditions: Coronary Artery Disease
Hypertriglyceridemia
Interventions: Drug: pradigastat (LCQ908)
Drug: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Study was terminated upon Part A interim analysis. Total 41 patients randomized to Part A i.e.17 patients in cohort 1 and 24 patients in Cohort 2.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Part A, Cohort 1: Pradigastat (LCQ908) Followed by Placebo Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All patients who randomized to this sequence received 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
Part A, Cohort 1: Placebo Followed by Pradigastat (LCQ908) Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All patients who randomized to this sequence received 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 20 mg (2 x 10-mg tablets) daily for two days
Part A, Cohort 2: Pradigastat (LCQ908) Followed by Placebo Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia.. All patients who randomized to this sequence received 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
Part A, Cohort 2: Placebo Followed by Pradigastat (LCQ908) Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia. All patients who randomized to this sequence received 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 20 mg (2 x 10-mg tablets) daily for two days

Participant Flow for 2 periods

Period 1:   Treatment Period 1 (5 Days [Day 1 - 5])
    Part A, Cohort 1: Pradigastat (LCQ908) Followed by Placebo     Part A, Cohort 1: Placebo Followed by Pradigastat (LCQ908)     Part A, Cohort 2: Pradigastat (LCQ908) Followed by Placebo     Part A, Cohort 2: Placebo Followed by Pradigastat (LCQ908)  
STARTED     8     9     11     13  
COMPLETED     7     9     10     11  
NOT COMPLETED     1     0     1     2  
Adverse Event                 0                 0                 1                 1  
Withdrawal by Subject                 0                 0                 0                 1  
Protocol deviation                 1                 0                 0                 0  

Period 2:   Treatment Period 2(5 Days[Day 36 - 40])
    Part A, Cohort 1: Pradigastat (LCQ908) Followed by Placebo     Part A, Cohort 1: Placebo Followed by Pradigastat (LCQ908)     Part A, Cohort 2: Pradigastat (LCQ908) Followed by Placebo     Part A, Cohort 2: Placebo Followed by Pradigastat (LCQ908)  
STARTED     7     9     10     11  
COMPLETED     7     9     10     11  
NOT COMPLETED     0     0     0     0  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set included all patients who received at least one dose of study drug.

Reporting Groups
  Description
Part A, Cohort 1: Pradigastat (LCQ908) Followed by Placebo Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All patients who randomized to this sequence received 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
Part A, Cohort 1: Placebo Followed by Pradigastat (LCQ908) Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All patients who randomized to this sequence received 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 20 mg (2 x 10-mg tablets) daily for two days
Part A, Cohort 2: Pradigastat (LCQ908) Followed by Placebo Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia.. All patients who randomized to this sequence received 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
Part A, Cohort 2: Placebo Followed by Pradigastat (LCQ908) Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia. All patients who randomized to this sequence received 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 20 mg (2 x 10-mg tablets) daily for two days
Total Total of all reporting groups

Baseline Measures
    Part A, Cohort 1: Pradigastat (LCQ908) Followed by Placebo     Part A, Cohort 1: Placebo Followed by Pradigastat (LCQ908)     Part A, Cohort 2: Pradigastat (LCQ908) Followed by Placebo     Part A, Cohort 2: Placebo Followed by Pradigastat (LCQ908)     Total  
Number of Participants  
[units: participants]
  8     9     11     13     41  
Age  
[units: years]
Mean (Standard Deviation)
  59.6  (6.67)     58.4  (8.79)     56.7  (9.79)     56.1  (8.85)     57.5  (8.5)  
Gender  
[units: Participants]
         
Female     2     4     4     6     16  
Male     6     5     7     7     25  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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 ]

2.  Primary:   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 ]

3.  Primary:   Time to Onset of Angina (Part A, Cohort 1)   [ Time Frame: Baseline and on day 5 of each of the two treatment periods ]

4.  Primary:   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 ]

5.  Primary:   Aortic Plaque Inflammation (Part B)   [ Time Frame: Baseline and on treatment day 85 +/- 3 days ]

6.  Secondary:   Number of Participants With Adverse Events (Part A, Cohort 1)   [ Time Frame: approximately 40 days ]

7.  Secondary:   Number of Participants With Adverse Events (Part A, Cohort 2)   [ Time Frame: approximately 40 days ]

8.  Secondary:   Postprandial Triglycerides (Part A, Cohort 1)   [ Time Frame: 0 hour (before breakfast), 2 and 4 hours post high-fat breakfast on day 5 ]

9.  Secondary:   Postprandial Triglycerides (Part A, Cohort 2)   [ Time Frame: 0 hour (before breakfast), 2 and 4 hours post high-fat breakfast on day 5 ]

10.  Secondary:   Pharmacokinetics of Pradigastat (LCQ908): Plasma Concentration (Part A)   [ Time Frame: Part A: Day 4 and day 5 of each treatment period ]

11.  Secondary:   Other Related Lipid Parameters (Part A)   [ Time Frame: Baseline, day 4 and day 5 of each treatment period ]

12.  Secondary:   Interleukin-6 (IL-6) Level (Part A)   [ Time Frame: Baseline, day 4 and day 5, of each treatment period ]

13.  Secondary:   C-reactive Protein (CRP) Level (Part A)   [ Time Frame: Baseline, day 4 and day 5, of each treatment period ]

14.  Secondary:   Adiponectin Level ( Part B)   [ Time Frame: Part B; Baseline, day 15, day 43 and day 85 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300
e-mail: trialandresults.registries@novartis.com



Responsible Party: Novartis ( 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