None listed
Conditions
Interventions
Drug : Before randomizing a subject on Day 1, the Investigator or designee should check if subjects comply with all inclusion/exclusion criteria. Each subject will receive an incremental identificatio
Sponsors
Sanofi-Aventis Korea
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Demography I 01. East Asian (ethnic Chinese, Japanese or Korean) male subjects, between 20 and 45 years of age, inclusive. I 02. Chinese, Japanese or Korean ethnicity, according to the following criteria: - Chinese; born in China or ethnic Chinese born outside of China, and a descendent of 4 ethnic Chinese grandparents who were all born in China - Japanese; born in Japan, have lived outside of Japan <10 years, and have parents and grandparents who are Japanese - Korean; born in Korea or ethnic Korean born outside of Korea, and a descendent of 4 ethnic Korean grandparents who were all born in Korea I 03. Body weight between 50.0 and 100.0 kg, inclusive, body mass index between 18.0 and 30.0 kg/m2, inclusive. Health status I 04. Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination). I 05. Normal vital signs after 10 minutes resting in supine position: - 95 mmHg < systolic bloodasymptotic pressure (SBP) <140 mmHg - 45 mmHg < diastolic blood pressure (DBP) <90 mmHg - 40 bpm < heart rate (HR) <100 bpm I 06. Standard 12-lead ECG parameters after 10 minutes resting in supine position in the following ranges; 120 ms < PR <220 ms, QRS <120 ms, QTc (Fridericia algorithm recommended) =450 ms, and normal ECG tracing unless the Investigator considers an ECG tracing abnormality to be not clinically relevant. I 07. Laboratory parameters within the normal range (or defined screening threshold for the Investigator site), unless the Investigator considers an abnormality to be clinically irrelevant for healthy subjects; however serum creatinine, alkaline phosphatase (ALP), hepatic enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT]), should not exceed the upper laboratory norm. Total bilirubin out of normal range can be acceptable if total bilirubin does not exceed 1.5 the upper limit with normal conjugated bilirubin values (unless the subject has documented Gilbert syndrome). Regulations I 08. Having given written informed consent prior to undertaking any study-related procedure. I 09. Not under any administrative or legal supervision. Specific to the study I 10. Male subject, whose partners are of childbearing potential (including lactating women), must accept to use, during sexual intercourse, a double contraception method according to the following algorithm: (condom) plus (intra-uterine device or hormonal contraceptive) from the inclusion up to 90 days after the last dosing. (See contraceptive guidance in Appendix A of the protocol) I 11. Male subject, whose partners are pregnant, must use, during sexual intercourse, a condom from the inclusion up to 90 days after the last dosing. (See contraceptive guidance in Appendix A of the protocol) I 12. Male subject has agreed not to donate sperm from the inclusion up to 3 months after the last dosing. (See contraceptive guidance in Appendix A of the protocol)
Exclusion criteria
Exclusion criteria: Medical history and clinical status E 01. Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, or infectious disease, or signs of acute illness. E 02. Frequent headaches and/or migraine, recurrent nausea and/or vomiting (for vomiting only: more than twice a month). E 03. Blood donation, any volume, within 2 months before inclusion. E 04. Symptomatic postural hypotension, irrespective of the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in systolic blood pressure =30 mmHg within 3 minutes when changing from supine to standing position. E 05. Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician. E 06. History or presence of drug or alcohol abuse (alcohol consumption more than 40 g per day on a regular basis). E 07. Smoking regularly more than 5 cigarettes or equivalent per week, unable to stop smoking during the study (occasional smoker can be enrolled). E 08. Excessive consumption of beverages containing xanthine bases (more than 4 cups or glasses per day). Interfering substance E 09. Any medication within 14 days or 5 times the elimination half-life or pharmacodynamic half-life of the medication, any medication which induces or inhibits drug metabolizing enzymes (DME) including but not limited to barbiturate and St John’s Wort within 1 month, any vaccination within the last 28 days, and any biologics (antibody or its derivatives) given within 4 months, before inclusion. General conditions E 10. 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. E 11. Any subject enrolled in or having participated, in [this or] any other clinical study involving an investigational medicinal product or in any other type of medical research within 6 months before inclusion. E 12. Any subject who cannot be contacted in case of emergency. E 13. Any subject who is the Investigator or any subinvestigator, research assistant, pharmacist, study coordinator, or other staff thereof, directly involved in conducting the study. Biological status E 14. Positive result on any of the following tests: hepatitis B surface antigen (HBs Ag), anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti HIV2 Ab), and tuberculosis. E 15. Positive result on urine drug screen (amphetamines, methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates). E 16. Positive alcohol breath test.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics: Primary endpoints: SAR442168 Pharmacokinetics (PK) parameters including Cmax, AUClast, AUC;Safety: Assessment of adverse events (AE) /treatment-emergent adverse events (TEAE), Physical examination and body weight, Clinical laboratory evaluations including hematology, biochemistry, coagulation, urinalysis, Vital signs (blood pressure and heart rate [HR] supine and standing), 12-lead electrocardiogram (ECG). | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics: Secondary endpoints: PRN2677 (metabolite) PK parameters including Cmax, AUClast, AUC;Exploratory Endpoints - Pharmacodynamics: Bruton's tyrosine kinase (BTK) occupancy of pre-dose and at 24 hours post-dose | — |
Countries
Korea, Republic of
Contacts
Public ContactIn-Jin Jang
Seoul National University Hospital
Outcome results
None listed