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The Study of Quantitative Serial Trends in Lipids With ApolpoproteinA-I Stimulation (SUSTAIN)

This study has been completed.
Sponsor:
Collaborator:
The Cleveland Clinic
Information provided by (Responsible Party):
Resverlogix Corp
ClinicalTrials.gov Identifier:
NCT01423188
First received: August 22, 2011
Last updated: September 19, 2012
Last verified: September 2012
  Purpose

This study is designed to provide an assessment of the change in baseline lipid parameters with RVX000222 after 12 weeks and 24 weeks of treatment when given in addition to optimized statin background therapy in subjects with low baseline HDL-C.


Condition Intervention Phase
Coronary Artery Disease
Dyslipidemia
Drug: RVX000222
Drug: Placebo RVX000222
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase IIb Multi-center, Double-blind, Randomized, Parallel Group, Placebo Controlled Clinical Trial for the Assessment of Lipid Trends and Safety of RVX000222 in Statin Treated Subjects With Low Baseline HDL-C Concentrations

Resource links provided by NLM:


Further study details as provided by Resverlogix Corp:

Primary Outcome Measures:
  • The percent change in HDL-C from baseline to 24 weeks for RVX000222 200 mg daily compared to placebo [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    To determine whether treatment with RVX000222 produces an increase in HDL-C at 24 weeks compared to placebo.


Secondary Outcome Measures:
  • Within treatment group percent change in HDL-C from baseline to 24 weeks for RVX000222 and placebo groups. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    To evaluate changes in other lipids such as HDL-C, LDL-C, non-HDL-C, apoB, TG and HDL subclasses over time within and between treatment groups.

  • The percent change in plasma apoA-I from baseline to 4 weeks, 12 weeks and 24 weeks for RVX000222 compared to placebo (within and between treatment groups). [ Time Frame: 4, 12 and 24 weeks ] [ Designated as safety issue: No ]
    To evaluate changes in plasma levels of apoA-I over time within and between treatment groups.

  • The percent change in LDL-C, non-HDL-C, apoB, TG and HDL subclasses from baseline to 4 weeks, 12 weeks and 24 weeks for RVX000222 compared to placebo (within and between treatment groups) [ Time Frame: 4, 12 and 24 weeks ] [ Designated as safety issue: No ]
    To evaluate changes in other lipids such as HDL-C, LDL-C, non-HDL-C, apoB, TG and HDL subclasses over time within and between treatment groups.

  • Incidence of adverse events by treatment group [ Time Frame: Participants will be followed for the duration of the study: 30 weeks (2 weeks screening, 24 weeks active treatment, 4 week follow-up) ] [ Designated as safety issue: Yes ]
    To evaluate the safety and tolerability of RVX000222.

  • The percent change in HDL-C from baseline to 4 weeks and 12 weeks for RVX000222 compared to placebo (within and between treatment groups) [ Time Frame: 4, 12 weeks ] [ Designated as safety issue: No ]
    To evaluate changes in other lipids such as HDL-C, LDL-C, non-HDL-C, apoB, TG and HDL subclasses over time within and between treatment groups.

  • The percent change in hsCRP from baseline to 12 weeks and 24 weeks for RVX000222 compared to placebo (within and between treatment groups). [ Time Frame: 12, 24 weeks ] [ Designated as safety issue: No ]
    To evaluate changes in hs-CRP over time within and between treatment groups.


Enrollment: 176
Study Start Date: August 2011
Study Completion Date: August 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RVX000222, 200 mg daily Drug: RVX000222
capsule, 200 mg, administer with food, 100 mg twice daily 10-12 hrs apart, 24 weeks
Placebo Comparator: Placebo Drug: Placebo RVX000222
capsule, administer with food, twice daily 10-12 hrs apart, 24 weeks

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 major component of HDL consists of apolipoprotein A-I (ApoA I). Recent intervention studies with synthetic HDL particles and recombinant ApoA-I have shown that HDL has the capacity to reverse coronary atherosclerosis. Increasing ApoA-I is likely to have a favorable effect on atherosclerotic plaque stability and size 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 ApoA-I transcription.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female patient's ≥ 18 years of age with or without documented coronary artery disease
  2. Women of child-bearing potential, that is, women not surgically sterilized and between menarche and 1 year post menopause, must test negative for pregnancy at the time of enrollment based on a serum pregnancy test and agree to use a reliable method of birth control (for example, use of oral contraceptives or levonorgestrel); or a reliable barrier method of birth control (diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices; partner with vasectomy; or abstinence) during the study and for one month following the last dose of study drug.
  3. HDL-C requirements. Current (Local lab within 60 days or central lab results prior to Visit 1): HDL-C of ≤45 mg/dL (1.17 mmol/L) for females, and HDL-C of ≤40 mg/dL (1.04 mmol/L) for males
  4. Taking statin therapy for at least 30 days prior to screening (Visit 1), and in the investigators opinion, an unlikely need for statin dose adjustment during the course of the study.
  5. In the opinion of the investigator patients currently on statin therapy other than atorvastatin (10mg, 20mg or 40mg) or rosuvastatin (5mg, 10mg or 20 mg) can be switched to rosuvastatin (5mg, 10mg or 20mg) at Visit 1.

Exclusion Criteria:

  1. Clinically significant heart disease which will require coronary bypass, PCI, cardiac transplantation, surgical repair and/or replacement during the course of the study.
  2. Coronary artery bypass graft (CABG) procedure within the past 90 days.
  3. Previous or current diagnosis of severe heart failure (NYHA Class III-IV) or a documented left ventricular ejection fraction (LVEF) of <25% as determined by contrast left ventriculography, radionuclide ventriculography or echocardiography the absence of an LVEF measurement in a patient without a previous or current diagnosis of heart failure does not prohibit entry into the study.
  4. Patients with evidence of cardiac electrophysiologic instability including a history of uncontrolled ventricular arrhythmias, uncontrolled atrial fibrillation/flutter or uncontrolled supraventricular tachycardias with a ventricular response heart rate of >100 beats per minute at rest within 4 weeks prior to Visit 1.
  5. Evidence of renal impairment as determined by any one of the following:

    1. serum creatinine >1.5 mg/dL (>133 micromol/L) at screening Visit 1
    2. a history of dialysis
    3. a history of nephritic syndrome
  6. Have hypertension that is uncontrolled defined as 2 consecutive measurements of sitting blood pressure of systolic >160 mm Hg or diastolic >95 mm Hg at Visit 1.
  7. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive beta-hCG laboratory test (≥5 mIU/mL).
  8. Current or recent (within 12 month prior to Visit 1) treatment with immunosuppressants (eg, Cyclosporine).
  9. Triglycerides >400 mg/dL at screening Visit 1.
  10. Atorvastatin >40 mg daily
  11. Rosuvastatin >20 mg daily
  12. Use of fibrates any dose or niacin/nicotinic acid 250 mg or more within 90 days prior to Visit 1.
  13. 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, ulcerative colitis, or any gastric bypass alteration.
  14. Evidence of hepatic disease as determined by any one of the following:

    • ALT, AST or GGT values >ULN by central lab at screening, Visit 1
    • a history of hepatic encephalopathy,
    • history of Hepatitis B, C or E,
    • a history of esophageal varices, or
    • a history of portocaval shunt.
  15. A total bilirubin that is >ULN by central lab at screening, Visit 1.
  16. History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.
  17. History or evidence of drug or alcohol abuse within the last 12 months.
  18. 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.
  19. Use of other investigational drugs and devices at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
  20. History of noncompliance to medical regimens or unwillingness to comply with the study protocol.
  21. Any condition that in the opinion of the investigator would confound the evaluation and interpretation of efficacy and/or safety data.
  22. Persons directly involved in the execution of this protocol
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01423188

Locations
South Africa
East Burger Street, Bloemfontein, South Africa, 9301
Westdene, Bloemfontein, South Africa, 9301
Goodwood, Cape Town, South Africa, 7460
Kraaifontein, Cape Town, South Africa, 7570
Pinelands, Cape Town, South Africa, 7405
Chatsworth, Durban, South Africa, 4092`
Congella, Durban, South Africa, 4001
Merebank, Durban, South Africa, 4052
Sydenham, Durban, South Africa, 4091
Tongaat, Durban, South Africa, 4400
Umhlanga, Durban, South Africa, 4321
Lenasia, Johannesburg, South Africa, 1827
Halfway House, Midrand, South Africa, 1685
Die Wilgers, Pretoria, South Africa, 0041
Eloffsdal, Pretoria, South Africa, 0084
Kuils River, Western Cape, South Africa, 7580
Parow, Western Cape, South Africa, 7500
Somerset West, Western Cape, South Africa, 7130
Stellenbosch, Western Cape, South Africa, 7600
Worcester, Western Cape, South Africa, 6850
Bloemfontein, South Africa, 9301
Cape Town, South Africa, 7505
Cape Town, South Africa, 7925
Johannesburg, South Africa, 1460
Western Cape, South Africa, 7646
Sponsors and Collaborators
Resverlogix Corp
The Cleveland Clinic
Investigators
Principal Investigator: Steve Nicholls, MBBS, PhD The Cleveland Clinic
  More Information

No publications provided by Resverlogix Corp

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Resverlogix Corp
ClinicalTrials.gov Identifier: NCT01423188     History of Changes
Other Study ID Numbers: RVX222-CS-008
Study First Received: August 22, 2011
Last Updated: September 19, 2012
Health Authority: South Africa: Medicines Control Council

Keywords provided by Resverlogix Corp:
ApolipoproteinA1
HDL-C
Atherosclerosis

Additional relevant MeSH terms:
Coronary Artery Disease
Coronary Disease
Dyslipidemias
Myocardial Ischemia
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Heart Diseases
Lipid Metabolism Disorders
Metabolic Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on November 23, 2014