A Double-blind, Randomised, Placebo-controlled, Rising Multiple Dose Study to Investigate the Tolerability, Steady-state Pharmacokinetics and Erythrocyte COMT Inhibition of BIA 3-202 in Healthy Volunteers.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Time of maximum observed concentration (tmax) - 3-O-methylnebicapone (BIA 3-270)
研究概览
简要总结
The purpose of this study is to investigate the tolerability and safety of three multiple dose regimens of nebicapone (BIA 3-202 100 mg, 200 mg, and 300 mg 6 times daily) in healthy volunteers. To characterise the steady-state pharmacokinetic and erythrocyte COMT inhibition profiles of nebicapone in healthy volunteers.
详细描述
Study design and methodology:
This was a single centre, human pharmacology (phase I), double-blind, randomised, placebo-controlled study of three multiple rising doses in three sequential groups of healthy volunteers. Subjects were screened for eligibility within 28 days of admission.
Screening:
Screening consisted of review of medical history, physical examination, neurological examination, vital signs, 12-lead ECG, clinical laboratory safety tests (haematology, coagulation, plasma biochemistry, urinalysis, HBsAg, anti-HCV Ab, anti-HIV-1 and anti-HIV-2 Ab), drugs of abuse and alcohol screen, and written informed consent. A pregnancy test was performed in all female subjects. The investigator was informed of the screening results prior to the subject's admission.
Treatment 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
- All
- 接受健康志愿者
- 是
入选标准
- •Male and female subjects aged between 18 and 45 years, inclusive.
- •Subjects of body mass index (BMI) between 19 and 28 kg/m2, inclusive.
- •Subjects who were healthy as determined by pre study medical history, physical examination, and 12- lead ECG.
- •Subjects who had clinical laboratory tests acceptable to the investigator.
- •Subjects who were negative for HBsAg, anti-HCV Ab and HIV-1 and HIV-2 Ab tests at screening.
- •Subjects who were negative for drugs of abuse and alcohol at screening and admission.
- •Subjects who were non-smokers or who smoke less than 10 cigarettes or equivalent per day.
- •Subjects who were able and willing to give written informed consent.
- •(If female) She was not of childbearing potential by reason of surgery or, if of childbearing potential, she used one of the following methods of contraception: double barrier, intrauterine device or abstinence.
排除标准
- •Subjects who did not conform to the above inclusion criteria, or
- •Subjects who had a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders.
- •Subjects who had a clinically relevant surgical history.
- •Subjects who had a clinically relevant family history.
- •Subjects who had a history of relevant atopy.
- •Subjects who had a history of relevant drug hypersensitivity.
- •Subjects who had a history of alcoholism or drug abuse.
- •Subjects who consumed more than 21 units of alcohol a week.
- •Subjects who had a significant infection or known inflammatory process on screening and/or admission.
- •Subjects who had acute gastrointestinal symptoms at the time of screening and/or admission (e.g., nausea, vomiting, diarrhoea, heartburn).
- •Subjects who had an acute infection such as influenza at the time of screening and/or admission.
- •Subjects who had used prescription drugs within 4 weeks of first dosing.
- •Subjects who had used oral contraceptives or over the counter medication excluding oral routine vitamins but including mega dose vitamin therapy within one week of first dosing.
- •Subjects who had used any investigational drug and/or participated in any clinical trial within 3 months of their first admission to this study.
- •Subjects who had previously received BIA 3-
- •Subjects who had donated and/or received any blood or blood products within the previous 2 months prior to screening.
- •Subjects who were vegetarians, vegans and/or have medical dietary restrictions.
- •Subjects who could not communicate reliably with the investigator.
- •Subjects who were unlikely to co-operate with the requirements of the study.
- •(If female) She was pregnant or breast-feeding.
- •(If female) She was of childbearing potential and she did not use an approved effective contraceptive method or she used oral contraceptives.
- •Subjects who were unwilling or unable to give written informed consent.
研究组 & 干预措施
Nebicapone 100 mg / Placebo
Treatment consisted of nebicapone/placebo repeated administration: one dose at 4-h intervals, for 7 full days: first dose at approximately 08 h (±1 h) on Day 1 and final dose at approximately 08 h (±1 h) on Day 8. Within each group (n=8), 2 volunteers were be randomised to receive placebo and the remaining 6 volunteers to receive nebicapone.
干预措施: Nebicapone (Drug)
Nebicapone 100 mg / Placebo
Treatment consisted of nebicapone/placebo repeated administration: one dose at 4-h intervals, for 7 full days: first dose at approximately 08 h (±1 h) on Day 1 and final dose at approximately 08 h (±1 h) on Day 8. Within each group (n=8), 2 volunteers were be randomised to receive placebo and the remaining 6 volunteers to receive nebicapone.
干预措施: Placebo (Drug)
Nebicapone 200 mg / Placebo
Treatment consisted of nebicapone/placebo repeated administration: one dose at 4-h intervals, for 7 full days: first dose at approximately 08 h (±1 h) on Day 1 and final dose at approximately 08 h (±1 h) on Day 8. Within each group (n=8), 2 volunteers were be randomised to receive placebo and the remaining 6 volunteers to receive nebicapone.
干预措施: Nebicapone (Drug)
Nebicapone 200 mg / Placebo
Treatment consisted of nebicapone/placebo repeated administration: one dose at 4-h intervals, for 7 full days: first dose at approximately 08 h (±1 h) on Day 1 and final dose at approximately 08 h (±1 h) on Day 8. Within each group (n=8), 2 volunteers were be randomised to receive placebo and the remaining 6 volunteers to receive nebicapone.
干预措施: Placebo (Drug)
Nebicapone 300 mg / Placebo
Treatment consisted of nebicapone/placebo repeated administration: one dose at 4-h intervals, for 7 full days: first dose at approximately 08 h (±1 h) on Day 1 and final dose at approximately 08 h (±1 h) on Day 8. Within each group (n=8), 2 volunteers were be randomised to receive placebo and the remaining 6 volunteers to receive nebicapone.
干预措施: Nebicapone (Drug)
Nebicapone 300 mg / Placebo
Treatment consisted of nebicapone/placebo repeated administration: one dose at 4-h intervals, for 7 full days: first dose at approximately 08 h (±1 h) on Day 1 and final dose at approximately 08 h (±1 h) on Day 8. Within each group (n=8), 2 volunteers were be randomised to receive placebo and the remaining 6 volunteers to receive nebicapone.
干预措施: Placebo (Drug)
结局指标
主要结局
Time of maximum observed concentration (tmax) - 3-O-methylnebicapone (BIA 3-270)
时间窗: Day 8
Mean 3-O-methylnebicapone (BIA 3-270) plasma concentration-time profiles following the last dose (Day 8) of a multiple-dose oral administration of nebicapone (100 mg, 200 mg or 300 mg, at 4-h intervals)
Time of maximum observed concentration (tmax) - Nebicapone
时间窗: Day 8
Mean nebicapone plasma concentration-time profiles following the last dose (Day 8) of a multiple-dose oral administration of nebicapone (100 mg, 200 mg or 300 mg, at 4-h intervals)
Area under the plasma concentration time curve extrapolated to infinity (AUC0-∞) - Nebicapone
时间窗: Day 8
Mean nebicapone plasma concentration-time profiles following the last dose (Day 8) of a multiple-dose oral administration of nebicapone (100 mg, 200 mg or 300 mg, at 4-h intervals)
Apparent terminal elimination half-life (t1/2) - Nebicapone
时间窗: Day 8
Mean nebicapone plasma concentration-time profiles following the last dose (Day 8) of a multiple-dose oral administration of nebicapone (100 mg, 200 mg or 300 mg, at 4-h intervals)
Maximum observed plasma concentration (Cmax) - Nebicapone
时间窗: Day 8
Mean nebicapone plasma concentration-time profiles following the last dose (Day 8) of a multiple-dose oral administration of nebicapone (100 mg, 200 mg or 300 mg, at 4-h intervals)
Maximum observed plasma concentration (Cmax) - 3-O-methylnebicapone (BIA 3-270)
时间窗: Day 8
Mean 3-O-methylnebicapone (BIA 3-270) plasma concentration-time profiles following the last dose (Day 8) of a multiple-dose oral administration of nebicapone (100 mg, 200 mg or 300 mg, at 4-h intervals)
Area under the plasma concentration time curve extrapolated to infinity (AUC0-∞) - 3-O-methylnebicapone (BIA 3-270)
时间窗: Day 8
Mean 3-O-methylnebicapone (BIA 3-270) plasma concentration-time profiles following the last dose (Day 8) of a multiple-dose oral administration of nebicapone (100 mg, 200 mg or 300 mg, at 4-h intervals)
Apparent terminal elimination half-life (t1/2) - 3-O-methylnebicapone (BIA 3-270)
时间窗: Day 8
Mean 3-O-methylnebicapone (BIA 3-270) plasma concentration-time profiles following the last dose (Day 8) of a multiple-dose oral administration of nebicapone (100 mg, 200 mg or 300 mg, at 4-h intervals)
次要结局
未报告次要终点