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

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

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

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease; Atherosclerosis; Dyslipidemia; Acute Coronary Syndrome
• Intervention / Treatment: Drug: RVX000222; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Covance Clinical Research Unit, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who meet the following criteria may be enrolled:

  1. Be men or women between 18 and 65 years old, inclusive
  2. Weigh between 60 kg and 110 kg, inclusive, and have a BMI ≥25 kg/m2.
  3. Healthy volunteers with normal or low HDL
  4. 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:

  1. 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.
  2. 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).
  3. Have had a clinically significant illness, in the opinion of the Investigator, within 30 days prior to Check-in.
  4. Have hypertension that is currently being treated, or uncontrolled hypertension
  5. Have a serum creatinine >1.5 mg/dL, hemoglobin <11.2 g/dL, or white blood cell count <4000/μL.
  6. Have positive test results for HIV, hepatitis A, B, or C.
  7. Have a positive result on drug screen testing.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Low-dose apabetalone (RVX000222) or placebo	Drug: RVX000222; RVX000222 twice daily (b.i.d.) for 28 days; Other Names: apabetalone; RVX-208; Drug: Placebo; Placebo twice daily (b.i.d.) for 28 days
Experimental: Arm B; apabetalone (RVX000222) Dose-escalation or placebo	Drug: RVX000222; RVX000222 twice daily (b.i.d.) for 28 days; Other Names: apabetalone; RVX-208; Drug: Placebo; Placebo twice daily (b.i.d.) for 28 days
Experimental: Arm C; high-dose apabetalone (RVX000222) or placebo	Drug: RVX000222; RVX000222 twice daily (b.i.d.) for 28 days; Other Names: apabetalone; RVX-208; Drug: Placebo; Placebo twice daily (b.i.d.) for 28 days

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Resverlogix Corp
• Investigators: Study Director: Allan Gordon, MD, PhD, Resverlogix Corp

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: October 7, 2008
• First Submitted That Met QC Criteria: October 7, 2008
• First Posted (Estimate): October 8, 2008

Study Record Updates

• Last Update Posted (Actual): November 4, 2022
• Last Update Submitted That Met QC Criteria: November 1, 2022
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Cholesterol; Dyslipidemia; Atherosclerosis; Apolipoprotein A-I; High density lipoprotein
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Vascular Diseases; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Lipid Metabolism Disorders; Cardiovascular Diseases; Dyslipidemias; Atherosclerosis; Acute Coronary Syndrome
• Other Study ID Numbers: RVX222-CS-003