A Rising Single Oral Dose Study to Investigate the Tolerability, Pharmacokinetics and Dopamine ß-hydroxylase (DßH) Inhibition Profile of BIA 5-453 in Healthy Male Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- % of subjects with at least one adverse event
研究概览
简要总结
The purpose of this study is to assess the safety and tolerability of BIA 5-453 after single oral doses
详细描述
Single centre, randomised, double-blind, placebo-controlled study of single ascending doses in 10 sequential groups of 8 healthy young male volunteers. Within each group (n=8), 6 volunteers were randomised to receive BIA 5-453 and the remaining 2 volunteers were randomised to receive placebo. A volunteer participated only in a single period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •A signed and dated informed consent form before any study-specific screening procedure was performed.
- •Aged between 18 and 45 years, inclusive.
- •Healthy 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).
- •Nonsmoker or smoker of fewer than 10 cigarettes per day as determined by history. Must have been able to abstain from smoking during the inpatient stay.
- •Have a high probability for compliance with and completion of the study.
排除标准
- •Medical History
- •Any significant cardiovascular (e.g. hypertension), hepatic, renal, respiratory (e.g. childhood asthma), gastrointestinal, endocrine (e.g. diabetes, dyslipidemia), immunologic, dermatological, haematological, neurologic, or psychiatric disease.
- •Acute disease state (e.g., nausea, vomiting, fever, diarrhoea) within 7 days before study day
- •History of drug abuse within 1 year before study day
- •History of alcoholism within 1 year before day
- •Consumption of more than 50 g of ethanol per day (12.5 cL glass of 10° [10%] wine = 12 g; 4 cL of aperitif, 42° [42%] whiskey = 17 g; 25 cL glass of 3° [3%] beer = 7.5 g; 25 cL glass of 6° [6%] beer = 15 g
- •History of any clinically important drug allergy.
- •Physical and Laboratory Findings
- •An automatic ECG QTc interval reading at screening or enrolment >450 ms.
- •Positive serologic findings for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies.
- •Positive findings of urine drug screen (eg, amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, MDMA [3,4-methylenedioxy-methamphetamine; ecstasy]).
- •Prohibited treatments
- •Prohibited Treatments: use of any investigational drug within 90 days or prescription drug within 30 days before investigational medical product (IMP) administration.
- •Consumption of any caffeine-containing products (e.g., coffee, tea, chocolate, or soda) in excess of 6 cups per day (or equivalent), of grapefruit, grapefruit-containing products, or alcoholic beverages within 72 before study day -
- •Use of any over-the-counter drugs including herbal supplements (except for the occasional use of acetaminophen [paracetamol], aspirin and vitamins ≤100% recommended daily allowance) within 7 days before IMP administration.
- •Donation of blood (ie 450 ml) within 90 days before study day 1.
研究组 & 干预措施
2 mg or placebo
BIA 5-453 or placebo
干预措施: BIA 5-453 (Drug)
2 mg or placebo
BIA 5-453 or placebo
干预措施: Placebo (Drug)
10 mg or placebo
BIA 5-453 or placebo
干预措施: BIA 5-453 (Drug)
10 mg or placebo
BIA 5-453 or placebo
干预措施: Placebo (Drug)
20 mg or placebo
BIA 5-453 or placebo
干预措施: BIA 5-453 (Drug)
20 mg or placebo
BIA 5-453 or placebo
干预措施: Placebo (Drug)
50 mg or placebo
BIA 5-453 or placebo
干预措施: BIA 5-453 (Drug)
50 mg or placebo
BIA 5-453 or placebo
干预措施: Placebo (Drug)
100 mg or placebo
BIA 5-453 or placebo
干预措施: BIA 5-453 (Drug)
100 mg or placebo
BIA 5-453 or placebo
干预措施: Placebo (Drug)
200 mg or placebo
BIA 5-453 or placebo
干预措施: BIA 5-453 (Drug)
200 mg or placebo
BIA 5-453 or placebo
干预措施: Placebo (Drug)
400 mg or placebo
BIA 5-453 or placebo
干预措施: BIA 5-453 (Drug)
400 mg or placebo
BIA 5-453 or placebo
干预措施: Placebo (Drug)
600 mg or placebo
BIA 5-453 or placebo
干预措施: BIA 5-453 (Drug)
600 mg or placebo
BIA 5-453 or placebo
干预措施: Placebo (Drug)
900 mg or placebo
BIA 5-453 or placebo
干预措施: BIA 5-453 (Drug)
900 mg or placebo
BIA 5-453 or placebo
干预措施: Placebo (Drug)
1200 mg or placebo
BIA 5-453 or placebo
干预措施: BIA 5-453 (Drug)
1200 mg or placebo
BIA 5-453 or placebo
干预措施: Placebo (Drug)
结局指标
主要结局
% of subjects with at least one adverse event
时间窗: through study completion, an average of 72 hours
Adverse events were continuously monitored from screening until the follow-up visit.
Time to reach Cmax (Tmax)
时间窗: Day 1 pre-dose then at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60, and 72 hours post-dose
Mean BIA 5-453 plasma pharmacokinetic parameters ± SD following single doses of 2, 10, 20, 50, 100, 200, 400, 600, 900 and 1200 mg of BIA 5-453 in 10 groups of 6 healthy volunteers each
Area under the plasma concentration-time curve from time 0 to the infinity (AUC0-∞)
时间窗: Day 1 pre-dose then at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60, and 72 hours post-dose
Mean BIA 5-453 plasma pharmacokinetic parameters ± SD following single doses of 2, 10, 20, 50, 100, 200, 400, 600, 900 and 1200 mg of BIA 5-453 in 10 groups of 6 healthy volunteers each
Maximum observed plasma concentration (Cmax)
时间窗: Day 1 pre-dose then at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60, and 72 hours post-dose
Mean BIA 5-453 plasma pharmacokinetic parameters ± SD following single doses of 2, 10, 20, 50, 100, 200, 400, 600, 900 and 1200 mg of BIA 5-453 in 10 groups of 6 healthy volunteers each
Area under the plasma concentration-time curve from time 0 to the time of last quantifiable concentration (AUC0-t)
时间窗: Day 1 pre-dose then at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60, and 72 hours post-dose
Mean BIA 5-453 plasma pharmacokinetic parameters ± SD following single doses of 2, 10, 20, 50, 100, 200, 400, 600, 900 and 1200 mg of BIA 5-453 in 10 groups of 6 healthy volunteers each
% of subjects by dose group with at least one treatment-emergent adverse event (TEAEs)
时间窗: through study completion, an average of 72 hours
Treatment emergent adverse events (TEAE) were defined as adverse events which did not exist before dosing and appeared in the 72 hours following treatment administration or which was present before administration and worsened in the 72 hours following treatment administration.
Apparent terminal elimination half-life (t1/2)
时间窗: Day 1 pre-dose then at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60, and 72 hours post-dose
Mean BIA 5-453 plasma pharmacokinetic parameters ± SD following single doses of 2, 10, 20, 50, 100, 200, 400, 600, 900 and 1200 mg of BIA 5-453 in 10 groups of 6 healthy volunteers each
次要结局
未报告次要终点