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

September 19, 2012 updated by: Resverlogix Corp

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
176

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • South Africa
      • Bloemfontein, South Africa, 9301
      • Cape Town, South Africa, 7925
      • Cape Town, South Africa, 7505
      • Johannesburg, South Africa, 1460
      • Western Cape, South Africa, 7646
    • Bloemfontein
      • East Burger Street, Bloemfontein, South Africa, 9301
      • Westdene, Bloemfontein, South Africa, 9301
    • Cape Town
      • Goodwood, Cape Town, South Africa, 7460
      • Kraaifontein, Cape Town, South Africa, 7570
      • Pinelands, Cape Town, South Africa, 7405
    • Durban
      • 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
    • Johannesburg
      • Lenasia, Johannesburg, South Africa, 1827
    • Midrand
      • Halfway House, Midrand, South Africa, 1685
    • Pretoria
      • Die Wilgers, Pretoria, South Africa, 0041
      • Eloffsdal, Pretoria, South Africa, 0084
    • Western Cape
      • 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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Drug: Placebo RVX000222
capsule, administer with food, twice daily 10-12 hrs apart, 24 weeks
Experimental: RVX000222, 200 mg daily
Drug: RVX000222
capsule, 200 mg, administer with food, 100 mg twice daily 10-12 hrs apart, 24 weeks

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The percent change in HDL-C from baseline to 24 weeks for RVX000222 200 mg daily compared to placebo
Time Frame: 24 weeks
To determine whether treatment with RVX000222 produces an increase in HDL-C at 24 weeks compared to placebo.
24 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Within treatment group percent change in HDL-C from baseline to 24 weeks for RVX000222 and placebo groups.
Time Frame: 24 weeks
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.
24 weeks
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
To evaluate changes in plasma levels of apoA-I over time within and between treatment groups.
4, 12 and 24 weeks
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
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.
4, 12 and 24 weeks
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)
To evaluate the safety and tolerability of RVX000222.
Participants will be followed for the duration of the study: 30 weeks (2 weeks screening, 24 weeks active treatment, 4 week follow-up)
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
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.
4, 12 weeks
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
To evaluate changes in hs-CRP over time within and between treatment groups.
12, 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Resverlogix Corp

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
The Cleveland Clinic

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Steve Nicholls, MBBS, PhD, The Cleveland Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 22, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 23, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 25, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 20, 2012

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 19, 2012

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RVX222-CS-008

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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