A double-blind, randomized, placebo-controlled, sequential ascending single-dose study to evaluate the pharmacokinetic and tolerability profiles of teriflunomide in healthy Korean subjects
- Conditions
- Diseases of the nervous system
- Registration Number
- KCT0000539
- Lead Sponsor
- Sanofi-Aventis Korea
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 36
1.Male or female Korean subjects, between 20 and 45 years of age, inclusive.
2. Body weight between 50.0 and 95.0 kg, inclusive, if male, and between 40.0 and 85.0 kg, inclusive, if female, body mass index between 18.0 and 30.0 kg/m2, inclusive.
3. Certified as healthy by a comprehensive clinical assessment (detailed medical history and
complete physical examination).
4. Normal vital signs after 10 minutes resting in supine position:
- 90 mmHg = systolic blood pressure (SBP) =139 mmHg
- 45 mmHg < diastolic blood pressure (DBP) <90 mmHg
- 40 bpm < heart rate (HR) <100 bpm
5. Normal standard 12-lead electrocardiogram (ECG) after 10 minutes resting in supine position; 120 ms6. Laboratory parameters within the normal range, unless the Investigator considers an abnormality to be clinically irrelevant for healthy subjects; however serum creatinine,alkaline phosphatase, hepatic enzymes (aspartate aminotransferases [AST] and ALT), and total bilirubin should not exceed the upper laboratory norm.
7. Women of child bearing potential and male subjects must agree that they will take means to reduce reproductive risk by agreeing to use a double method of contraception.Acceptable methods of contraception are defined for this protocol as:
* For male:
- True abstinence: when this is in line with the preferred and usual lifestyle of the subject (Periodic abstinence [eg, calendar, ovulation, symptothermal, post ovulation methods] and withdrawal are not acceptable methods of contraception).
- Male sterilization (with the appropriate post vasectomy documentation of the absence of sperm in the ejaculate).
- Use of condoms throughout the study, in addition to spermicides is recommended.
* For women of child bearing potential:
- True abstinence: when this is in line with the preferred and usual lifestyle of the subject (Periodic abstinence [eg, calendar, ovulation, symptothermal, post ovulation methods] and withdrawal are not acceptable methods of contraception).
- Highly effective oral contraceptives, such as biphasic and triphasic oral contraceptives are considered adequate. Progestogene only pills or mini pills” which have demonstrated lower high efficacy will not be acceptable.
- Injectable hormones (ie, Depo-Provera), hormonal implants, transdermal patches or intrauterine device (IUD) or intrauterine systems (IUS) or intravaginal ring(NuvaRing) which have demonstrated efficacy comparable to high efficacy oral contraceptives are adequate.
8. Having given written informed consent prior to undertaking any study-related procedure.
9. In compliance with the recommendations of the national laws in force relating to biomedical research.
10. Not under any administrative or legal supervision.
01. Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynecologic (if female), or infectious disease, or signs of acute illness.
2. Frequent headaches and/or migraine, recurrent nausea and/or vomiting (more than twice a month).
3. Blood donation, any volume, within 3 months before inclusion.
4. Symptomatic postural hypotension, irrespective of the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in SBP =20 mmHg within 3 minutes when changing from supine to standing position.
5. Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician.
6. History or presence of drug or alcohol abuse (alcohol consumption more than 40 g per day).
7. Smoking more than 5 cigarettes or equivalent per day, unable to stop smoking during the study.
8. Excessive consumption of beverages containing xanthine bases (more than 4 cups or glasses per day).
9. If female, pregnancy (defined as positive ß-HCG blood test), breast-feeding.
10. Any medication (including St John’s Wort) within 14 days before inclusion or within 5 times the elimination half-life or pharmacodynamic half-life of the medication, with the exception of hormonal contraception; any vaccination within the last 28 days.
11. Any subject who, in the judgment of the Investigator, is likely to be noncompliant during the study, or unable to cooperate because of a language problem or poor mental development.
12. Any subject in the exclusion period of a previous study according to applicable regulations.
13. Any subject who cannot be contacted in case of emergency.
14. Any subject who is the Investigator or any subinvestigator, research assistant, pharmacist,study coordinator, or other staff thereof,directly involved in conducting the study.
15. Positive result on any of the following tests: hepatitis B surface antigen, anti-hepatitis C virus antibodies, anti-human immunodeficiency virus antibodies.
16. Positive result on urine drug screen (amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates).
17. Positive alcohol breath test.
18. Any consumption of citrus (grapefruit, orange, etc) or their juices within 5 days before inclusion.
19. Subjects (male or female) who disagree to use an appropriate contraception method during the study until the plasma teriflunomide concentrations are equal to or less than 0.25 µg/mL at the end of the study or beyond.
20. Although the risk of male-mediated embryo-fetal toxicity through teriflunomide treatment is low, male subject wishing to father a child or having a partner of child bearing potential not protected by effective contraceptive method.(If a female partner of a male subject who is required to adopt contraceptive measures becomes pregnant during the trial, she must be followed up until the outcome of the pregnancy is known).
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The pharmacokinetics of teriflunomide after ascending single oral doses of 7 mg, 14 mg, 28mg
- Secondary Outcome Measures
Name Time Method The tolerability and safety of teriflunomide after ascending single oral doses of 7 mg, 14mg, 28mg