Characterization of Multi-dose RVX000222 in Combination With Statin Treatment in Dyslipidemia

NCT01863225 | Terminated Phase 2

• 1 other identifier: RVX222-CS-009
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to characterize the pharmacokinetics of multi-dose RVX000222 and atorvastatin and rosuvastatin when either statin is administered in combination with RVX000222 in subjects with dyslipidemia.

Conditions

Dyslipidemia; Coronary Artery Disease

Outcome Measures

Primary Outcomes (1)

• Characterization of the pharmacokinetics of RVX000222 capsule formulation in combination with either atorvastatin or rosuvastatin in patients with dyslipidemia.

  The plasma concentration-time profile of RVX000222 capsule formulation and its metabolites on Days 1 and 14 of 200 mg daily RVX000222 in combination with either atorvastatin or rosuvastatin, including pharmacokinetic parameters Cmax, Tmax, Cmin, AUC0-12, AUC12-24, AUC0 24, and metabolite ratio.

  14 days

Secondary Outcomes (2)

• Characterization of the pharmacokinetics of atorvastatin and rosuvastatin when either is administered in combination with RVX000222 capsule formulation to patients with dyslipidemia.

  14 days

• Evaluation of safety and tolerability of RVX000222 capsule formulation administered in combination with stable doses of either atorvastatin or rosuvastatin in patients with dyslipidemia.

  14

Study Arms (4)

Group A

EXPERIMENTAL

RVX000222 200 mg (100 mg b.i.d.) + Atorvastatin 40 mg

Drug: RVX000222; Drug: Atorvastatin

Group B

EXPERIMENTAL

RVX000222 200 mg (100 mg b.i.d.) + Rosuvastatin 20 mg

Drug: RVX000222; Drug: Rosuvastatin

Group C

EXPERIMENTAL

RVX000222 200 mg (100 mg b.i.d.) + Atorvastatin 80 mg

Drug: RVX000222; Drug: Atorvastatin

Group D

EXPERIMENTAL

RVX000222 200 mg (100 mg b.i.d.) + Rosuvastatin 40 mg

Drug: RVX000222; Drug: Rosuvastatin

Interventions

RVX000222 DRUG

capsule, 200 mg, administer with food, 100 mg twice daily 10-12 hrs apart, 14-days

Also known as: RVX-208

Group A; Group B; Group C; Group D

Rosuvastatin DRUG

20 mg daily, 28-42 days

Group B

Atorvastatin DRUG

40 mg daily, 28-42 days

Group A

Eligibility Criteria

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

You may qualify if:

• Male and female patients ≥ 18 to ≤ 65 years of age with or without documented coronary artery disease.
• Taking statin therapy for at least 30 days prior to Screening (Visit 1).
• In the opinion of the investigator, patient currently on statin therapy other than atorvastatin 40 mg or rosuvastatin 20 mg or atorvastatin 80 mg or rosuvastatin 40 mg who could be switched to one of these regimens at Visit 1 for the duration of the study.

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.
• Have a body mass index (BMI) greater than 36 kg/m2.
• Patients of East Asian descent (due to pharmacological food effect noted for rosuvastatin).
• 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
• Have hypertension that is uncontrolled defined as 2 consecutive measurements of sitting blood pressure of systolic \>160 mmHg or diastolic \> 95 mmHg at Visit 1.
• Women of child-bearing potential who do not agree to use two reliable methods of birth control during the study and for one month following the last dose of study drug, or 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 ß-hCG laboratory test (≥ 5 IU/L) at the time of enrollment. Where women of child-bearing potential are defined as women not surgically sterilized and between menarche and 1 year post menopause, and a reliable method of birth control includes use of oral contraceptives or levonorgestrel; or a reliable barrier method of birth control (diaphragms; cervical caps; condoms; intrauterine devices; partner with vasectomy; or abstinence).
• Current or recent (within 12 month prior to Visit 1) treatment with immunosuppressants (e.g., Cyclosporine).
• Triglycerides \> 4.5 mmol/L at screening Visit 1.
• Use of fibrates of 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
• A total bilirubin that is \> ULN by local laboratory at screening, Visit 1

Sponsors & Collaborators

• Resverlogix Corp: lead
• South Australian Health and Medical Research Institute: collaborator

Study Sites (1)

Royal Adelaide Hospital / CMAX

Adelaide, South Australia, 5000, Australia

Location

MeSH Terms

Conditions

Dyslipidemias; Coronary Artery Disease

Interventions

apabetalone; Rosuvastatin Calcium; Atorvastatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrroles; Azoles; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Dr. Sepehr Shakib

  Royal Adelaide Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2013
• First Posted: May 27, 2013
• Study Start: May 1, 2013
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: May 12, 2015

Record last verified: 2015-05

Locations

AU (1)