Coronary Artery DiseasePhase 2SUSTAINNCT01423188
The Study of Quantitative Serial Trends in Lipids With ApolpoproteinA-I Stimulation
A Phase 2 study testing RVX000222 in people with Coronary Artery Disease and Dyslipidemia, run by Resverlogix Corp at 25 sites in South Africa.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease, Dyslipidemia
- What is being tested?
- RVX000222
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 176 participants
- Where
- 25 sitesSouth Africa
- Study dates
- Aug 2011to Aug 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 30Show fewer
- 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.
- 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.
- 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.
- A total bilirubin that is >ULN by central lab at screening, Visit 1.
- 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.
- History or evidence of drug or alcohol abuse within the last 12 months.
- 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.
- 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.
- History of noncompliance to medical regimens or unwillingness to comply with the study protocol.
- Any condition that in the opinion of the investigator would confound the evaluation and interpretation of efficacy and/or safety data.
- Persons directly involved in the execution of this protocol
Trial locations and contacts
25 sites in 1 country.
25 sites in 1 country
South Africa25 sites
Study site
Bloemfontein, 9301
Study site
Cape Town, 7505
Study site
Cape Town, 7925
Study site
Chatsworth, Durban, 4092'
Study site
Die Wilgers, Pretoria, 0041
Study site
East Burger Street, Bloemfontein, 9301
Study site
Eloffsdal, Pretoria, 0084
Study site
Goodwood, Cape Town, 7460
Study site
Halfway House, Midrand, 1685
Study site
Johannesburg, 1460
Study site
Kraaifontein, Cape Town, 7570
Study site
Kuils River, Western Cape, 7580
Study site
KwaKhangela, Durban, 4001
Study site
Lenasia, Johannesburg, 1827
Study site
Merebank, Durban, 4052
Study site
Parow, Western Cape, 7500
Study site
Pinelands, Cape Town, 7405
Study site
Somerset West, Western Cape, 7130
Study site
Stellenbosch, Western Cape, 7600
Study site
Sydenham, Durban, 4091
Study site
Tongaat, Durban, 4400
Study site
Umhlanga, Durban, 4321
Study site
Westdene, Bloemfontein, 9301
Study site
Western Cape, 7646
Study site
Worcester, Western Cape, 6850
About this study
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
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.
Read the 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.
- Conditions
- Coronary Artery Disease, Dyslipidemia
- Being tested
- RVX000222, Placebo RVX000222
- Keywords
- ApolipoproteinA1, HDL-C, Atherosclerosis
- Medical subject headings
- Coronary Artery Disease, Dyslipidemias, Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RVX000222Drug
capsule, 200 mg, administer with food, 100 mg twice daily 10-12 hrs apart, 24 weeks
Placebo RVX000222Drug
capsule, administer with food, twice daily 10-12 hrs apart, 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| RVX000222, 200 mg daily | Experimental | Not described Receives: Drug: RVX000222 |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo RVX000222 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 weeks
Secondary outcomes (6)
Within treatment group percent change in HDL-C from baseline to 24 weeks for RVX000222 and placebo groups.
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.
Measured: 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).
To evaluate changes in plasma levels of apoA-I over time within and between treatment groups.
Measured: 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)
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.
Measured: 4, 12 and 24 weeks
Incidence of adverse events by treatment group
To evaluate the safety and tolerability of RVX000222.
Measured: 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)
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.
Measured: 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).
To evaluate changes in hs-CRP over time within and between treatment groups.
Measured: 12, 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2011 (estimated)
- Study startAug 2011
- Primary completionJun 2012
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- 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
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 176 participants (actual)
Sponsor and investigators
- Lead sponsor
- Resverlogix Corp
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- The Cleveland Clinic
- Responsible party
- Sponsor
- Investigators
- Steve Nicholls, MBBS, PhD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01423188
- Sponsor's protocol ID
- RVX222-CS-008
- Acronym
- SUSTAIN
- Status last verified
- Sep 2012
- First submitted
- 22 Aug 2011
- Last updated
- 20 Sep 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 22349989
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01423188
- Acronym / sponsor ID
- SUSTAIN / RVX222-CS-008
- Conditions
- Coronary Artery Disease, Dyslipidemia
- Keywords
- ApolipoproteinA1, HDL-C, Atherosclerosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 176 participants (actual)
- Lead sponsor
- Resverlogix CorpIndustry (pharma, biotech, devices)
- Collaborators
- The Cleveland Clinic
- Study start
- Aug 2011
- Primary completion
- Jun 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 25 Aug 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RVX000222, 200 mg daily | Experimental | Drug: RVX000222 |
| Placebo | Placebo comparator | Drug: Placebo RVX000222 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (30 listed)
- 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:
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 |
|---|---|---|
| RVX000222capsule, 200 mg, administer with food, 100 mg twice daily 10-12 hrs apart, 24 weeks | Drug | RVX000222, 200 mg daily |
| Placebo RVX000222capsule, administer with food, twice daily 10-12 hrs apart, 24 weeks | Drug | Placebo |
Primary outcome
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.
6 secondary outcomes
Within treatment group percent change in HDL-C from baseline to 24 weeks for RVX000222 and placebo groups.
Time frame: 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
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
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)
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2012.
- Derived from this study: PubMed 22349989Nicholls 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.
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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.
Steve Nicholls, MBBS, PhD principal investigator
The Cleveland Clinic
25 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RVX000222 in people with Coronary Artery Disease and Dyslipidemia, run by Resverlogix Corp at 25 sites in South Africa.
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 5 inclusion and 30 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: finished, as of the sponsor's last update on 20 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in South Africa. 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The percent change in HDL-C from baseline to 24 weeks for RVX000222 200 mg daily compared to placebo (time frame: 24 weeks). 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 NCT01423188, which also lists 1 linked publication.
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 20 Sep 2012.