ASSERT: Clinical Trial for Dose Finding and Safety of RVX000222 in Subjects With Stable Coronary Artery Disease

Sponsor

Resverlogix Corp (Industry)

Overall Status

Completed

CT.gov ID

NCT01058018

Collaborator

(none)

299

Enrollment

Location

Arms

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate dose range, safety and efficacy of RVX000222 in subjects with stable coronary artery disease.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerosis Coronary Artery Disease	Drug: RVX000222 Drug: Placebo	Phase 2

Detailed Description

One-third of the US population, almost 80 million adults, have cardiovascular disease and mortality associated with heart disease still remains as a leading cause of death around the world. The major risk factors for cardiovascular disease associated with atherosclerosis is dyslipidemia, characterized by high levels of low density lipoprotein (LDL) and/or low levels of high density lipoprotein (HDL). The widespread use of statins in patients at risk for cardiovascular disease has led to lower LDL levels but has had little effect on HDL levels. HDL has a well established role in atherosclerosis and cardiovascular disease protection. HDL mediates the removal of cholesterol from the atherosclerotic plaques for elimination from the body. The cardioprotective component of HDL consists of apolipoprotein A1 (ApoA1). Recent intervention studies with synthetic HDL particles and recombinant ApoA1 have shown that HDL has the capacity to reverse coronary atherosclerosis. Increasing ApoA1 is likely to have a favorable effect on atherosclerotic plaque size and stability, and on cardiovascular diseases. RVX000222 is a member of a novel class of small molecules that are candidates for the treatment of dyslipidemia by increasing plasma levels of HDL through increased ApoA1 transcription.

Study Design

Study Type:

Interventional

Actual Enrollment :

299 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Phase II Multi-center, Double-blind, Randomized, Parallel Group, Placebo-controlled Clinical Trial for Dose-finding and Safety Study of RVX000222 in Subjects With Stable Coronary Artery Disease

Study Start Date :

Dec 1, 2009

Actual Primary Completion Date :

Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A - 100 mg per day RVX000222 Arm A: Treatment with RVX000222 at 50 mg twice daily for 12 weeks, orally with meals in the morning and in the evening, 10 to 12 hours apart.	Drug: RVX000222 RVX000222 twice a day for 12 weeks Other Names: RVX-208 apabetalone
Experimental: B - 200 mg per day RVX000222 Arm B: Treatment with RVX000222 100 mg twice daily for 12 weeks, orally with meals in the morning and in the evening, 10 to 12 hours apart.	Drug: RVX000222 RVX000222 twice a day for 12 weeks Other Names: RVX-208 apabetalone
Experimental: C - 300 mg per day RVX000222 Arm C: Treatment with RVX000222 150 mg twice daily for 12 weeks, orally with meals in the morning and in the evening, 10 to 12 hours apart.	Drug: RVX000222 RVX000222 twice a day for 12 weeks Other Names: RVX-208 apabetalone
Placebo Comparator: D - Placebo Arm D: Treatment with placebo for 12 weeks, orally with meals in the morning and in the evening, 10 to 12 hours apart.	Drug: Placebo Placebo twice a day for 12 weeks

Outcome Measures

Primary Outcome Measures

The percent change in ApoA1 from baseline to 12 weeks post-randomization for each treatment arm compared to placebo. [from baseline to 12 weeks post-study drug treatment]

Secondary Outcome Measures

Compare the dose and time response relationships for major lipids (ApoA1, total cholesterol, HDL-C, LDL-C, non-HDL-C, TG, ApoB, LDL, and HDL-subclasses) over 4, 8 and 12 weeks time course. [4, 8 and 12 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men and women at least 18 years of age.
If female, non-pregnant (as determined by a negative serum pregnancy test at Screening), non-lactating, and not of childbearing-potential or willing to practice acceptable form of birth control. If male, be willing to practice an acceptable form of birth control.
Documented coronary artery disease such as stable angina, coronary artery bypass graft, myocardial infarction within the past 90 days, or a history of percutaneous coronary intervention greater than 90 days before randomization
Taking a stable dose of statin therapy for at least 30 days prior to enrollment into the study with, in the investigators opinion, an unlikely need for statin dose adjustment during the course of the study.
Have given signed informed consent to participate in this study

Exclusion Criteria:

A female who is pregnant or lactating?
Participated in any research study, or been on an investigational drug within the last 30 days?
Currently have any of the following Illnesses:

Heart disease needing surgical repair
Coronary Artery bypass surgery in the last 90 days
PCI or Stent placement in the last 90 days
Left Ventricular ejection fraction
Evidence of cardiac electrophysiologic instability
Renal Impairment
Uncontrolled Hypertension 160/95 (2 consecutive Measurements)
Triglycerides ≥ 400 mg/dl (at Screening)
Liver: Total bilirubin > ULN, ALT/AST 1.5 > ULN at Screening
History of Drug or Alcohol abuse in last 12 months
History of Malignancy ≤ 5 years

Currently taking any immunosuppressant's
Any changes in stain therapy doses in last 30 days
Use of Fibrates at any dose
Use of Niacin ≥ 250 mg per day
Have any medical or surgical condition which might significantly alter the absorption, distribution, metabolism or excretion of medication including but not limited to any of the following: cholecystitis, Crohn's disease or ulcerative colitis?
Have any surgical or medical condition which in the opinion of the Investigator may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study?
Using other investigational drugs and devices at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer?
Have a history of noncompliance to medical regimens or unwillingness to comply with the study protocol?
Have any condition that in the opinion of the investigator would confound the evaluation and interpretation of efficacy and/or safety data?
Directly involved in the execution of this study?