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

NCT01423188 | Completed Phase 2 DMC

• 1 other identifier: RVX222-CS-008
• Study Type: interventional
• Target: 176
• Locations: 1 country
• Sites: 25

Brief Summary

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.

Conditions

Coronary Artery Disease; Dyslipidemia

Keywords

ApolipoproteinA1; HDL-C; Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• The percent change in HDL-C from baseline to 24 weeks for RVX000222 200 mg daily compared to placebo

  To determine whether treatment with RVX000222 produces an increase in HDL-C at 24 weeks compared to placebo.

  24 weeks

Secondary Outcomes (6)

• Within treatment group percent change in HDL-C from baseline to 24 weeks for RVX000222 and placebo 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).

  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)

  4, 12 and 24 weeks

• Incidence of adverse events by treatment group

  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)

  4, 12 weeks

Study Arms (2)

RVX000222, 200 mg daily

EXPERIMENTAL

Drug: RVX000222

Placebo

PLACEBO COMPARATOR

Drug: Placebo RVX000222

Interventions

RVX000222 DRUG

capsule, 200 mg, administer with food, 100 mg twice daily 10-12 hrs apart, 24 weeks

RVX000222, 200 mg daily

Placebo RVX000222 DRUG

capsule, administer with food, twice daily 10-12 hrs apart, 24 weeks

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patient's ≥ 18 years of age with or without documented coronary artery disease
• 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.
• 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
• 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.
• 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.

You may not qualify if:

• Clinically significant heart disease which will require coronary bypass, PCI, cardiac transplantation, surgical repair and/or replacement during the course of the study.
• Coronary artery bypass graft (CABG) procedure within the past 90 days.
• 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.
• 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.
• Evidence of renal impairment as determined by any one of the following:
• serum creatinine \>1.5 mg/dL (\>133 micromol/L) at screening Visit 1
• a history of dialysis
• a history of nephritic syndrome
• 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.
• 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).
• Current or recent (within 12 month prior to Visit 1) treatment with immunosuppressants (eg, Cyclosporine).
• Triglycerides \>400 mg/dL at screening Visit 1.
• Atorvastatin \>40 mg daily
• Rosuvastatin \>20 mg daily
• Use of fibrates any dose or niacin/nicotinic acid 250 mg or more within 90 days prior to Visit 1.

Sponsors & Collaborators

• Resverlogix Corp: lead
• The Cleveland Clinic: collaborator

Study Sites (25)

Unknown Facility

East Burger Street, Bloemfontein, 9301, South Africa

Location

Unknown Facility

Westdene, Bloemfontein, 9301, South Africa

Location

Unknown Facility

Goodwood, Cape Town, 7460, South Africa

Location

Unknown Facility

Kraaifontein, Cape Town, 7570, South Africa

Location

Unknown Facility

Pinelands, Cape Town, 7405, South Africa

Location

Unknown Facility

Chatsworth, Durban, 4092', South Africa

Location

Unknown Facility

KwaKhangela, Durban, 4001, South Africa

Location

Unknown Facility

Merebank, Durban, 4052, South Africa

Location

Unknown Facility

Sydenham, Durban, 4091, South Africa

Location

Unknown Facility

Tongaat, Durban, 4400, South Africa

Location

Unknown Facility

Umhlanga, Durban, 4321, South Africa

Location

Unknown Facility

Lenasia, Johannesburg, 1827, South Africa

Location

Unknown Facility

Halfway House, Midrand, 1685, South Africa

Location

Unknown Facility

Die Wilgers, Pretoria, 0041, South Africa

Location

Unknown Facility

Eloffsdal, Pretoria, 0084, South Africa

Location

Unknown Facility

Kuils River, Western Cape, 7580, South Africa

Location

Unknown Facility

Parow, Western Cape, 7500, South Africa

Location

Unknown Facility

Somerset West, Western Cape, 7130, South Africa

Location

Unknown Facility

Stellenbosch, Western Cape, 7600, South Africa

Location

Unknown Facility

Worcester, Western Cape, 6850, South Africa

Location

Unknown Facility

Bloemfontein, 9301, South Africa

Location

Unknown Facility

Cape Town, 7505, South Africa

Location

Unknown Facility

Cape Town, 7925, South Africa

Location

Unknown Facility

Johannesburg, 1460, South Africa

Location

Unknown Facility

Western Cape, 7646, South Africa

Location

Related Publications (1)

• Nicholls SJ, Gordon A, Johannson J, Ballantyne CM, Barter PJ, Brewer HB, Kastelein JJ, Wong NC, Borgman MR, Nissen SE. ApoA-I induction as a potential cardioprotective strategy: rationale for the SUSTAIN and ASSURE studies. Cardiovasc Drugs Ther. 2012 Apr;26(2):181-7. doi: 10.1007/s10557-012-6373-5.

  PMID: 22349989 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Dyslipidemias; Atherosclerosis

Interventions

apabetalone

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Steve Nicholls, MBBS, PhD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2011
• First Posted: August 25, 2011
• Study Start: August 1, 2011
• Primary Completion: June 1, 2012
• Study Completion: August 1, 2012
• Last Updated: September 20, 2012

Record last verified: 2012-09

Locations

ZA (25)