Pharmacokinetics and Safety Study of Probucol by Multiple Administration in Healthy Male Subjects

The Pharmacokinetics and Safety Study of Probucol by Multiple Administration in Healthy Male Subjects

The Objectives of this study is to evaluate the pharmacokinetics and safety of multiple oral doses of probucol in healthy male subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Probucol

Detailed Description

This is a single dose, single period, multiple administration, open-labeled trial in one investigation center.

The screening examination will be completed from Day -14 to Day -2 before investigational medicinal product (IMP) administration. The subjects will be hospitalized on Day -1. From Day 1 (the next day), the subjects will receive probucol twice daily (BID). for 14 consecutive days. On Day 18, the subjects can be discharged after the safety evaluation. The follow-up visit will occur on Day 6, 9, 12, 15, 19, 27 (totally 41 days) after the final dosing day.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Clinical Pharmacology Research Center, Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Chinese.
2. Gender: Male.
3. Age 20 to 40 years, (at time of informed consent).
4. Body mass index [BMI, body weight (kg) / height (m)2] between 19 and 26 kg/m2, inclusive.
5. Nonsmokers (or former smokers): Urinary cotinine level satisfying the criteria for a nonsmoker established by the trial site (at time of screening examination).
6. Subjects judged by the investigator to be healthy based on the medical history, physical examination, vital signs, 12 lead ECG, the results of serological test (HIV/HCV Ab, HBsAg and Syphilis Ab) and clinical laboratory tests, etc.

Exclusion Criteria:

1. Subjects with hypersensitivity or a history of hypersensitivity to any drug (any prescription or over-the-counter [OTC] drug)

2. Subjects who meet any of the following lipid criteria in the fasting state (at time of screening examination)

   • LDL-C: ≥ 140 mg/dL
   • TC: ≥ 220 mg/dL
   • HDL-C: < 40 mg/dL

   • TG: ≥ 150 mg/dL

     • LDL-C value will be directly measured or calculated by the Friedewald formula. Friedewald Formula: LDL-C = TC - HDL-C - TG/5 (When TG value is less than 400 mg/dL) LDL-C value will be directly measured when TG value is 400 mg/dL or greater.
3. Subjects with electrocardiogram (ECG) results showing AV block or with both QTc and QRS width outside the standard values of the ECG laboratory (at time of screening examination)
4. Subjects with alcohol or drug dependence or a history of drug abuse
5. Subjects who have a positive result in an infectious disease test or urine drug test (at time of screening examination)

6. Use of any of the following within the specified period prior to scheduled investigational medicinal product (IMP) administration

   • All other prescription and OTC drugs (within 2 weeks prior to scheduled IMP administration)
   • Alcohol and caffeine-containing products (within 1 week prior to scheduled IMP administration)
7. Use of any other investigational drug within 16 weeks prior to scheduled IMP administration in the present trial
8. Plasmapheresis or plateletpheresis within 2 weeks or whole blood collection (blood donation, etc) cumulatively exceeding 200 mL within 4 weeks, 400 mL within 12 weeks, or 1200 mL within 1 year prior to scheduled IMP administration
9. Subjects whose body weight is less than 50 kg (at time of screening examination)
10. Subjects who are scheduled for examination or treatment at any other hospital or clinic during the trial period
11. Subjects otherwise judged by the investigator or sub investigator to be inappropriate for inclusion in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: probucol in healthy male subjects; multiple oral doses of probucol in single group of healthy male subjects	Drug: Probucol; 250mg (1 tablet) bid. p.o for 14 consecutive days; Other Names: Lorelco

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameters	Pharmacokinetic parameters: Day 1 (Plasma PK parameters over the 24h dosing period)： Cmax, Cmax1, Cmax2, tmax1, tmax2, AUC (0-10)h, AUC (10-24)h, AUC24h, C24h; Day3，5，7，9，11，12，13：C24h; Day 14： Cmax, Cmax1, Cmax2, tmax1, tmax2, AUC (0-10)h, AUC (10-24)h, AUC24h, C24h, Clast, tlast, t1/2,z,Lambdaz, DF, CL/F, Vz/F, AUC_%Extrap; Accumulation evaluation parameters: Rpred, R14,ac(AUC24h), R14,ac(Cmax), R14,ac(C24h), R14,ac[AUC(0-10h)], R14,ac[AUC(10-24h)], R14,ac(Cmax1), R14,ac(Cmax2).	Day 1, 3, 5, 7, 9, 11, 12, 13, 14

Collaborators and Investigators

• Sponsor: Otsuka Beijing Research Institute
• Investigators: Principal Investigator: Pei Hu, PHD, Clinical Pharmacology Research Center of Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (ACTUAL): April 1, 2012
• Study Completion (ACTUAL): January 1, 2013

Study Registration Dates

• First Submitted: January 11, 2012
• First Submitted That Met QC Criteria: May 1, 2012
• First Posted (ESTIMATE): May 3, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): June 5, 2013
• Last Update Submitted That Met QC Criteria: June 4, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Pharmacokinetics; healthy male subjects; Probucol
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Protective Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Antioxidants; Probucol
• Other Study ID Numbers: 009-11-803-01