Effect of Age-gender on the Pharmacokinetic and Pharmacodynamic Profiles of BIA 5 1058. An Open-label, Parallel Group, Multiple Dose 10-day Study.
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 61
- 主要终点
- Maximum observed plasma concentration (Cmax)
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All subjects (young and elderly):
- •A signed and dated informed consent form before any study-specific screening procedure was performed;
- •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);
- •Non-smoker or ex-smokers for at least 3 months at screening;
- •BMI between 18 and 30 kg/m2, inclusive;
- •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;
- •Clinical laboratory test results clinically acceptable at screening and admission to the study;
- •Negative screen for alcohol and drugs of abuse at screening and admission to the study;
- •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;
- •Refraining from donating sperm throughout the study.
- •Young subjects only:
- •Males and females aged between 18 and 40 years, inclusive.
- •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;
- •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;
- •If of childbearing potential, negative serum pregnancy test at screening and negative urine pregnancy test on admission to the study.
- •Elderly subjects only:
- •Males and females older than 65 years, inclusive.
排除标准
- •All subjects (young and elderly):
- •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;
- •Clinically relevant surgical history;
- •History of relevant atopy or drug hypersensitivity;
- •History of alcoholism or drug abuse;
- •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];
- •Significant infection or known inflammatory process at screening or admission to study;
- •Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to the study;
- •Previous use of BIA 5-1058;
- •Use of any investigational drug or participation in any clinical trial within 90 days prior to screening;
- •Participation in more than 2 clinical trials within the 12 months prior to screening;
- •Donation or reception of any blood or blood products within the 3 months prior to screening;
- •Vegetarians, vegans or other medical dietary restrictions;
- •Not able to communicate reliably with the Investigator;
- •Unlikely to co-operate with the requirements of the study.
- •Not using an accepted effective method of contraception;
- •Refusing to refrain from donating sperm throughout the study.
- •Young subjects only:
- •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:
- •Pregnant or breastfeeding;
- •Not using an accepted effective contraceptive method or using oral contraceptives.
- •Elderly subjects only:
- •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.
研究组 & 干预措施
BIA 5-1058 1200 mg (Part I)
Subjects received 1200 mg of BIA 5-1058 once a day (od), in fasting conditions, for 10 days
干预措施: BIA 5-1058 (Drug)
BIA 5-1058 400 mg (Part II)
Subjects received 400 mg of BIA 5-1058 od, in fasting conditions, for 10 days.
干预措施: BIA 5-1058 (Drug)
结局指标
主要结局
Maximum observed plasma concentration (Cmax)
时间窗: Up to 4 weeks
Pharmacokinetic analysis Blood samples for PK analysis were taken at the following times: On D1: before BIA 5-1058 dosing (pre-dose), and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h post-dose (before the second administration on D2). On D3, D7, D8 and D9: before BIA 5-1058 dosing. From D10 to D13: before BIA 5-1058 dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (D11), 36 (D11), 48 (D12), 60 (D12) and 72h post-dose (D13).
Time of occurrence of Cmax (tmax)
时间窗: Up to 4 weeks
Pharmacokinetic analysis Blood samples for PK analysis were taken at the following times: On D1: before BIA 5-1058 dosing (pre-dose), and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h post-dose (before the second administration on D2). On D3, D7, D8 and D9: before BIA 5-1058 dosing. From D10 to D13: before BIA 5-1058 dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (D11), 36 (D11), 48 (D12), 60 (D12) and 72h post-dose (D13).
Area under the plasma concentration-time curve from time zero to 24 hours after last dosing (AUC0-24)
时间窗: Up to 4 weeks
Pharmacokinetic analysis Blood samples for PK analysis were taken at the following times: On D1: before BIA 5-1058 dosing (pre-dose), and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h post-dose (before the second administration on D2). On D3, D7, D8 and D9: before BIA 5-1058 dosing. From D10 to D13: before BIA 5-1058 dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (D11), 36 (D11), 48 (D12), 60 (D12) and 72h post-dose (D13).
Apparent total body clearance (CL/F)
时间窗: Up to 4 weeks
Pharmacokinetic analysis Blood samples for PK analysis were taken at the following times: On D1: before BIA 5-1058 dosing (pre-dose), and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h post-dose (before the second administration on D2). On D3, D7, D8 and D9: before BIA 5-1058 dosing. From D10 to D13: before BIA 5-1058 dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (D11), 36 (D11), 48 (D12), 60 (D12) and 72h post-dose (D13).
Area under the plasma concentration-time curve (AUC) from time zero to the last sampling time at which the drug concentration was at or above the lower limit of quantification (AUC0-t)
时间窗: Up to 4 weeks
Pharmacokinetic analysis Blood samples for PK analysis were taken at the following times: On D1: before BIA 5-1058 dosing (pre-dose), and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h post-dose (before the second administration on D2). On D3, D7, D8 and D9: before BIA 5-1058 dosing. From D10 to D13: before BIA 5-1058 dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (D11), 36 (D11), 48 (D12), 60 (D12) and 72h post-dose (D13).
Apparent terminal half-life (t½)
时间窗: Up to 4 weeks
Pharmacokinetic analysis Blood samples for PK analysis were taken at the following times: On D1: before BIA 5-1058 dosing (pre-dose), and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h post-dose (before the second administration on D2). On D3, D7, D8 and D9: before BIA 5-1058 dosing. From D10 to D13: before BIA 5-1058 dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (D11), 36 (D11), 48 (D12), 60 (D12) and 72h post-dose (D13).
次要结局
未报告次要终点