Safety, Pharmacokinetic Study of RVX000222 in Healthy Subjects and Subjects With Low HDL Cholesterol

Study Overview
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Brief Summary
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The purpose of this study is to investigate an oral formulation of RVX000222 for safety, pharmacokinetic and efficacy in healthy subjects.

Detailed Description
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One-third of the US population, almost 80 million adults, have cardiovascular disease and mortality associated with heart disease which still remains 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). 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. RVX000222 is a member of a novel class of small molecules that are candidates for the treatment of dyslipidemia by increasing plasma levels of ApoA-I and HDL.

Official Title
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A Safety, Pharmacokinetic, and Pharmacodynamic Assessment of 28-Day Oral Dosing of RVX000222 in Healthy Subjects and Subjects With Low High Density Lipoprotein (HDL)

Conditions
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Atherosclerosis, Dyslipidemia, Acute Coronary Syndrome, Cardiovascular Disease

Intervention / Treatment
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* Drug: RVX000222
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who meet the following criteria may be enrolled: Be men or women between 18 and 65 years old, inclusive Weigh between 60 kg and 110 kg, inclusive, and have a BMI ≥25 kg/m2. Healthy volunteers with normal or low HDL 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 an acceptable form of birth control. If male, be willing to practice an acceptable form of birth control. Exclusion Criteria: Subjects who meet any of the following criteria will not be enrolled: Have presently, or have a history of, clinically significant disease, including cardiovascular, gastrointestinal, renal, hepatic, pulmonary, endocrine, hematologic, vascular, immunologic, metabolic, neurological, or collagen disease, as judged by the Investigator. Have active cholecystitis or gallbladder symptoms within 60 days prior to Check-in (subjects who have had a cholecystectomy are not excluded from this study). Have had a clinically significant illness, in the opinion of the Investigator, within 30 days prior to Check-in. Have hypertension that is currently being treated, or uncontrolled hypertension Have a serum creatinine >1.5 mg/dL, hemoglobin <11.2 g/dL, or white blood cell count <4000/μL. Have positive test results for HIV, hepatitis A, B, or C. Have a positive result on drug screen testing.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Low-dose apabetalone (RVX000222) or placebo | Drug: RVX000222<br>* RVX000222 twice daily (b.i.d.) for 28 days<br>* Other names: apabetalone;Drug: Placebo<br>* Placebo twice daily (b.i.d.) for 28 days<br>|
| Experimental: Arm B<br>apabetalone (RVX000222) Dose-escalation or placebo | Drug: RVX000222<br>* RVX000222 twice daily (b.i.d.) for 28 days<br>* Other names: apabetalone;Drug: Placebo<br>* Placebo twice daily (b.i.d.) for 28 days<br>|
| Experimental: Arm C<br>high-dose apabetalone (RVX000222) or placebo | Drug: RVX000222<br>* RVX000222 twice daily (b.i.d.) for 28 days<br>* Other names: apabetalone;Drug: Placebo<br>* Placebo twice daily (b.i.d.) for 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety, pharmacokinetics and changes in lipid parameters from baseline and placebo. |  | 1-month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cholesterol, High density lipoprotein, Dyslipidemia, Atherosclerosis, Apolipoprotein A-I