To Compare the Effect of Concomitant Administration of Probucol and Cilostazol With Probucol Single Treatment on the Atherosclerosis Related Markers (Including the Thickness of the Achilles Tendon) and Evaluate Safety (Based on Atorvastatin Treatment) in Severe Hypercholesterolemia Subject

To evaluate the effect of concomitant administration of Probucol and Cilostazol (based on Atorvastatin treatment) on the atherosclerosis related markers (including the thickness of the Achilles tendon) in severe hypercholesterolemia subject, through the observation of the thickness of the Achilles tendon, the thickness of mean carotid intima-media, anti-oxidation biomarkers and serum lipid profile.

Study Overview

• Status: Unknown
• Conditions: Severe Hypercholesterolemia
• Intervention / Treatment: Drug: Atorvastatin, Probucol, Cilostazol

Detailed Description

Multicenter, randomized, controlled, single-blinded, three parallel arms study. Group A: Atorvastatin + Probucol-placebo + Cilostazol-placebo Group B: Atorvastatin + Probucol + Cilostazol-placebo Group C: Atorvastatin + Probucol + Cilostazol

• Study Type: Interventional
• Enrollment (Anticipated): 250
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Anzhen hospital
    • Contact: Jie Lin, Dr; Phone Number: 00861064412431
    • Principal Investigator: Jie Lin, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The subject whose voluntary written informed consent is obtained for participation in this study;
2. 18≤age≤70；
3. The subject with low-density lipoprotein cholesterol (LDL-C) ≥ 4.66 mmol/L (180 mg/dL) (the highest level either pre-treatment or on treatment);
4. The subject with ATT≥9mm.

Exclusion Criteria:

1. The subject with homozygous familial hyperlipidemia;
2. The subject who took Probucol within 6 months before the screening test;
3. The subject who took Cilostazol within 1 month before the screening test;
4. The subject who took Ezetimibe within 1 month before the screening test;
5. The subject who hoped to treat with Ezetimibe within this study period;
6. The subject being treated with Cyclosporine;
7. The subject with a history of hypersensitivity to Probucol and Cilostazol;
8. The subject with a triglyceride (TG) level greater than 4.52 mmol/L (400 mg/dL);
9. The subject with diabetes: HbA1c level greater than 8.4% (NGSP);
10. The subject with New York Heart Association (NYHA) classification: Class III and IV;
11. The subject with a QTc interval greater than 450 msec (male) or 470 msec (female);
12. The subject with serious ventricular arrythmias (frequent episodes of multifocal ventricular extrasystole);
13. The subject with atrial fibrillation (including paroxysmal atrial fibrillation);
14. The subject with congestive cardiac failure or unstable angina;

15. The subject with liver and renal functions that satisfy the following criteria within 28 days prior to start of the investigational medicinal product (IMP) administration.

    • AST ≥100 IU/L, ALT≥100 IU/L
    • Serum creatinine ≥1.5 mg/dL (133 µmol/L)
16. The subject who are participating in another clinical trial;
17. Woman during pregnancy or potential pregnancy, and breastfeeding;
18. Women of childbearing potential who are not agree to use an appropriate method of contraception;
19. The subject who are not considered by the Investigators to be appropriate to participate in this study for any other reasons.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Probucol,Cilostazol; Atorvastatin + Probucol-placebo + Cilostazol-placebo
Placebo Comparator: Cilostazol; Atorvastatin + Probucol+ Cilostazol-placebo	Drug: Atorvastatin, Probucol, Cilostazol
Active Comparator: Probucol, Cilostazol; Atorvastatin + Probucol + Cilostazol	Drug: Atorvastatin, Probucol, Cilostazol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the effect of concomitant administration of Probucol and Cilostazol on the mean achilles tendon thickness (ATT)	at Month 6, 12 and 24

Secondary Outcome Measures

Outcome Measure	Time Frame
the additional effect of concomitant administration of Probucol and Cilostazol on mean carotid intima-media thickness (IMT)	at Month 12 and 24
the preventive effect of concomitant administration of Probucol and Cilostazol on the incidence of cerebrovascular and cardiovascular events (including intervention)	2 years
the effect of concomitant administration of Probucol and Cilostazol on biomarkers	2 years
the safety of Probucol or concomitant administration of Probucol and Cilostazol as determined by physical examination, vital signs, adverse events (AEs), laboratory examinations and 12-lead electrocardiogram (ECGs)	2 years

Collaborators and Investigators

• Sponsor: Otsuka Beijing Research Institute
• Investigators: Principal Investigator: Jie Lin, Dr, Anzhen hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Anticipated): April 1, 2017
• Study Completion (Anticipated): April 1, 2017

Study Registration Dates

• First Submitted: March 25, 2014
• First Submitted That Met QC Criteria: March 25, 2014
• First Posted (Estimate): March 28, 2014

Study Record Updates

• Last Update Posted (Estimate): March 31, 2014
• Last Update Submitted That Met QC Criteria: March 27, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: intima-media thickness; the Achilles tendon
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Antimetabolites; Neuroprotective Agents; Protective Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antioxidants; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Atorvastatin; Cilostazol; Probucol
• Other Study ID Numbers: 260-13-806-01