effect of age-gender on the pharmacokinetic and pharmacodynamic profiles of bia 5 1058

Conditions: Pulmonary Arterial Hypertension

Summary: the purpose of this study is to determine the effect of age on the pharmacokinetics (pk) profile of bia 5-1058 at steady state after multiple oral doses

this was a single-centre, open-label, parallel group, non-randomised, two-part multiple dose 10-day study in healthy young and elderly male and female subjects. the study comprised a screening evaluation between 2 and 28 days before the first investigational medicinal product (imp) administration, a hospitalisation period of 15 days comprising a treatment period of 10 days, and a follow-up visit approximately 7 days after discharge. part 1: subjects received 1200 mg of bia 5-1058 once a day (od), in fasting conditions, for 10 days part 2 : subjects received 400 mg of bia 5-1058 od, in fasting conditions, for 10 days.

Eligibility criteria:
inclusion criteria: all subjects (young and elderly): 1. a signed and dated informed consent form before any study-specific screening procedure was performed; 2. healthy male and female subjects as determined by the investigator on the basis of medical history, physical examination, clinical laboratory test results, vital signs and digital 12-lead electrocardiogram (ecg); 3. non-smoker or ex-smokers for at least 3 months at screening; 4. bmi between 18 and 30 kg/m2, inclusive; 5. negative tests for hepatitis b surface antigen (hbsag), anti-hepatitis c virus antibodies (hcv ab) and anti-human immunodeficiency virus antibodies (hiv-1 and hiv-2 ab) at screening; 6. clinical laboratory test results clinically acceptable at screening and admission to the study; 7. negative screen for alcohol and drugs of abuse at screening and admission to the study; if male: 8. using an effective method of contraception with a pregnant partner or partner of childbearing potential (condom or occlusive cap \[diaphragm or cervical or vault caps\] with spermicidal foam or gel or film or cream or suppository; true abstinence; or vasectomy) throughout the study; 9. refraining from donating sperm throughout the study. young subjects only: 10. males and females aged between 18 and 40 years, inclusive. if female: 11. no childbearing potential by reason of surgery or at least 1 year post-menopause (i.e., 12 months post last menstrual period), or menopause confirmed by follicle-stimulating hormone (fsh) testing; 12. if of childbearing potential, using an effective non-hormonal method of contraception \[intrauterine device or intrauterine system; condom or occlusive cap (diaphragm or cervical or vault caps) with spermicidal foam or gel or film or cream or suppository; true abstinence; or vasectomized male partner, provided that he is the sole partner of that subject\] for all the duration of the study; 13. if of childbearing potential, negative serum pregnancy test at screening and negative urine pregnancy test on admission to the study. elderly subjects only: 14. males and females older than 65 years, inclusive. exclusion criteria: all subjects (young and elderly): 1. clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders; 2. clinically relevant surgical history; 3. history of relevant atopy or drug hypersensitivity; 4. history of alcoholism or drug abuse; 5. consumption of more than 14 units of alcohol a week \[1 unit corresponds to 1 glass of 12° wine (10 cl), 1 glass of 45° pastis (2.5 cl), 1 glass of 40° whisky (2.5 cl), 1 glass of 12° champagne (10 cl), 1 glass of 18°aperitif drink (7 cl) or one 25-cl glass of 5°beer\]; 6. significant infection or known inflammatory process at screening or admission to study; 7. acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to the study; 8. previous use of bia 5-1058; 9. use of any investigational drug or participation in any clinical trial within 90 days prior to screening; 10. participation in more than 2 clinical trials within the 12 months prior to screening; 11. donation or reception of any blood or blood products within the 3 months prior to screening; 12. vegetarians, vegans or other medical dietary restrictions; 13. not able to communicate reliably with the investigator; 14. unlikely to co-operate with the requirements of the study. if male: 15. not using an accepted effective method of contraception; 16. refusing to refrain from donating sperm throughout the study. young subjects only: 17. use of medicines within 2 weeks of admission that could affect the safety or other study assessments, in the investigator's opinion; if female of childbearing potential: 18. pregnant or breastfeeding; 19. not using an accepted effective contraceptive method or using oral contraceptives. elderly subjects only: 20. for elderly subjects, previously prescribed medications that interfered with absorption, distribution, metabolism, and excretion or safety/tolerability evaluation of bia 5-1058 and adrenal or renal function were prohibited; however, previously prescribed medications that did not interfere with absorption, distribution, metabolism, and excretion or safety/tolerability evaluation of bia 5-1058, adrenal or renal function and which could not interfere with the objectives of the study were allowed if the dose regimen had been stable for at least 4 weeks and was expected to remain stable throughout the study. such concomitant medications were to be reviewed and mutually agreed upon by the sponsor and the investigator.