Coronary Artery DiseasePhase 2NCT01474434

Efficacy of LCQ908 on Cardiovascular Risk

A Phase 2 study testing pradigastat (LCQ908) in people with Coronary Artery Disease and Hypertriglyceridemia, run by Novartis Pharmaceuticals at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

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

Who is it for?: Ages 40 to 80 years
Conditions the study is for: Coronary Artery Disease, Hypertriglyceridemia
What is being tested?: pradigastat (LCQ908)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 41 participants
Where: 1 siteUnited States
Study dates: Dec 2011to Jun 2014
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Novartis Investigative Site
Pasadena, California, 91105

Other trials in United States

About this study

Official title: 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.

Read the 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.

Conditions: Coronary Artery Disease, Hypertriglyceridemia
Being tested: pradigastat (LCQ908), Placebo
Keywords: coronary artery disease,, LCQ908,, hyperlipidemia,, hypertriglyceridemia,, pradigastat
Medical subject headings: Coronary Artery Disease, Hypertriglyceridemia, Hyperlipidemias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

pradigastat (LCQ908)Drug
Also called Pradigastat
pradigastat tablets were supplied to the investigators at dose strengths of 10 mg and 20 mg as individual patient packs.
PlaceboDrug
matching placebo tablets

Study groups in NCT01474434
Study group	Role	What they receive
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 Receives: 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 Receives: Drug: pradigastat (LCQ908); Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline and on treatment day 85 +/- 3 days

Secondary outcomes (9)

Number of Participants With Adverse Events (Part A, Cohort 1)
Measured: approximately 40 days
Number of Participants With Adverse Events (Part A, Cohort 2)
Measured: approximately 40 days
Postprandial Triglycerides (Part A, Cohort 1)
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.
Measured: 0 hour (before breakfast), 2 and 4 hours post high-fat breakfast on day 5
Postprandial Triglycerides (Part A, Cohort 2)
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.
Measured: 0 hour (before breakfast), 2 and 4 hours post high-fat breakfast on day 5
Pharmacokinetics of Pradigastat (LCQ908): Plasma Concentration (Part A)
Measured: Part A: Day 4 and day 5 of each treatment period
Other Related Lipid Parameters (Part A)
Measured: Baseline, day 4 and day 5 of each treatment period
Interleukin-6 (IL-6) Level (Part A)
Measured: Baseline, day 4 and day 5, of each treatment period
C-reactive Protein (CRP) Level (Part A)
Measured: Baseline, day 4 and day 5, of each treatment period
Adiponectin Level ( Part B)
Measured: Part B; Baseline, day 15, day 43 and day 85

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2011Jun 2014

First posted18 Nov 2011 (estimated)
Study startDec 2011
Primary completionJun 2014
Study completionJun 2014

Why it stopped: The study was terminated based on interim analysis. See detailed description.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 41 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01474434
Sponsor's protocol ID: CLCQ908A2213
Status last verified: Mar 2016
First submitted: 9 Nov 2011
Last updated: 14 Apr 2016
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 14 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-blind, Placebo Controlled Study to Assess the Efficacy of LCQ908 on Cardiovascular Risk
ClinicalTrials.gov ID: NCT01474434
Acronym / sponsor ID: CLCQ908A2213
Conditions: Coronary Artery Disease, Hypertriglyceridemia
Keywords: coronary artery disease,, LCQ908,, hyperlipidemia,, hypertriglyceridemia,, pradigastat
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: The study was terminated based on interim analysis. See detailed description.
Enrolment: 41 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Dec 2011
Primary completion: Jun 2014 (actual)
Study completion: Jun 2014 (actual)
First posted: 18 Nov 2011 (estimated)
Results: Posted 14 Apr 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Pradigastat (LCQ908) followed by placebo	Experimental	Drug: pradigastat (LCQ908), Drug: PlaceboPradigastat 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
Placebo followed by pradigastat (LCQ908)	Experimental	Drug: pradigastat (LCQ908), Drug: PlaceboPlacebo (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

Who may qualify

Ages: 40 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (6 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
pradigastat (LCQ908)Also: Pradigastatpradigastat tablets were supplied to the investigators at dose strengths of 10 mg and 20 mg as individual patient packs.	Drug	Placebo followed by pradigastat (LCQ908), Pradigastat (LCQ908) followed by placebo
Placebomatching placebo tablets	Drug	Placebo followed by pradigastat (LCQ908), Pradigastat (LCQ908) followed by placebo

Primary outcome

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

9 secondary outcomes

Number of Participants With Adverse Events (Part A, Cohort 1)
Time frame: approximately 40 days
Number of Participants With Adverse Events (Part A, Cohort 2)
Time frame: approximately 40 days
Postprandial Triglycerides (Part A, Cohort 1)
Time frame: 0 hour (before breakfast), 2 and 4 hours post high-fat breakfast on day 5
Postprandial Triglycerides (Part A, Cohort 2)
Time frame: 0 hour (before breakfast), 2 and 4 hours post high-fat breakfast on day 5
Pharmacokinetics of Pradigastat (LCQ908): Plasma Concentration (Part A)
Time frame: Part A: Day 4 and day 5 of each treatment period
Other Related Lipid Parameters (Part A)
Time frame: Baseline, day 4 and day 5 of each treatment period
Interleukin-6 (IL-6) Level (Part A)
Time frame: Baseline, day 4 and day 5, of each treatment period
C-reactive Protein (CRP) Level (Part A)
Time frame: Baseline, day 4 and day 5, of each treatment period
Adiponectin Level ( Part B)
Time frame: Part B; Baseline, day 15, day 43 and day 85

Results and safety

Results posted to the registry on 14 Apr 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part A, Cohort 1: Pradigastat (LCQ908) Followed by Placebo	8	7
Part A, Cohort 1: Placebo Followed by Pradigastat (LCQ908)	9	9
Part A, Cohort 2: Pradigastat (LCQ908) Followed by Placebo	11	10
Part A, Cohort 2: Placebo Followed by Pradigastat (LCQ908)	13	11

Primary outcome: 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. Least squares mean (Standard Error). Unit: myocardial perfusion reserve index

Measure	Part A, Cohort 1: Pradigastat (LCQ908) n = 13	Part A, Cohort 1: Placebo n = 12
Value	-0.22 (0.24)	0.32 (0.24)

Population analysed: Efficacy analysis set - Patients who took \> 80% of study drug as assessed by drug accountability, had no major protocol deviations, and had a valid assessment of MPRi at both baseline and post-treatment visits. Patients who had no baseline or post-treatment MPRi data in 1 of 2 periods were excluded from the analysis.

Primary outcome: 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. Least squares mean (Standard Error). Unit: minute

Measure	Part A, Cohort 1: Pradigastat (LCQ908) n = 11	Part A, Cohort 1: Placebo n = 14
Value	-1.52 (0.46)	-1.00 (0.40)

Population analysed: Efficacy analysis set- Patients who took \> 80% of study drug as assessed by drug accountability, had no major protocol deviations, and had a valid assessment of total exercise duration at both baseline and post-treatment visits. Patients who had no baseline or post-treatment exercise duration data in 1 of 2 periods were excluded from the analysis.

Primary outcome: Time to Onset of Angina (Part A, Cohort 1)

Time frame: Baseline and on day 5 of each of the two treatment periods

Population analysed: The study was terminated based on the interim analysis after patients completed Part A. This outcome measure was not part of interim analysis; hence it is not done. .

Primary outcome: 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

Population analysed: The study was terminated based on the interim analysis after patients completed Part A. This outcome measure was not part of interim analysis; hence it is not done. .

9 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A, Cohort 1: Pradigastat (LCQ908)	0 of 17 (0%)	16 of 17 (94.1%)	Not reported
Part A, Cohort 1: Placebo	0 of 17 (0%)	6 of 17 (35.3%)	Not reported
Part A, Cohort 2: Pradigastat (LCQ908)	0 of 24 (0%)	22 of 24 (91.7%)	Not reported
Part A, Cohort 2: Placebo	1 of 24 (4.2%)	13 of 24 (54.2%)	Not reported

Limitations and caveats (from the sponsor): 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

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing pradigastat (LCQ908) in people with Coronary Artery Disease and Hypertriglyceridemia, run by Novartis Pharmaceuticals at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Apr 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the 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). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01474434.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2016.