A Double-blind, Randomised, Placebo-controlled, Rising Multiple Dose Study in Healthy Volunteers to Investigate the Effect of BIA 6-512 at Steady-state on the Levodopa Pharmacokinetics When Administered in Combination With a Single-dose of Levodopa/Benserazide 200/50 mg or With a Single-dose of Levodopa/Benserazide 200/50 mg Plus a Single-dose of Nebicapone 150 mg
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Day 4 - AUC from time zero to 8 h post-dose (AUC0-τ)
研究概览
简要总结
The purpose of this study was to determine whether the administration of BIA 6-512 (25 mg, 50 mg, 75 mg and 100 mg) at steady-state affects the pharmacokinetics of levodopa when administered in combination with a single-dose of immediate release levodopa/benserazide 200/50 mg or with a single-dose of immediate release levodopa/benserazide 200/50 mg plus a single-dose of nebicapone 150 mg.
详细描述
Single centre, double-blind, randomised, placebo-controlled, rising multiple dose study in four sequential groups of healthy male and female subjects. Eligible subjects were admitted to the Human Pharmacology Unit (UFH)on the day prior to receiving the first study medication. Starting in the morning of Day 1 (first dose), subjects received BIA 6-512/Placebo thrice daily until the morning of Day 5 (last dose). Concomitantly with the morning dose of BIA 6-512/Placebo on Day 4, a levodopa/benserazide 200/50 mg (Madopar® 250) single-dose was administered. On Day 5, a Madopar® 250 single-dose and a nebicapone 150 mg single-dose were administered concomitantly with the morning dose of BIA 6-512/Placebo. In the morning of Day 4 and Day 5, products were administered in fasting conditions of at least 8 hours and subjects remained fasted until 2 h post-dose. Subjects were resident in the UFH from admission (Day 0) until at least 24 h post last dose (Day 6); then, they were discharged and returned for the follow-up visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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 or female subjects aged between 18 and 45 years, inclusive.
- •Subjects of body mass index (BMI) between 19 and 30 kg/m2, inclusive.
- •Subjects who were healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG.
- •Subjects who had negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab at screening
- •Subjects who had clinical laboratory test results clinically acceptable at screening and admission.
- •Subjects who had a negative screen for alcohol and drugs of abuse at screening and admission.
- •Subjects who were non-smokers or who smoked ≤ 10 cigarettes or equivalent per day.
- •Subjects who were able and willing to gave 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.
- •(If female) She had a negative urine pregnancy test at screening and admission.
排除标准
- •Subjects who had a 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.
- •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 14 units of alcohol a week.
- •Subjects who had a significant infection or known inflammatory process on screening or admission.
- •Subjects who had acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission.
- •Subjects who had used medicines within 2 weeks of admission that may affect the safety or other study assessments, in the investigator's opinion.
- •Subjects who had previously participated in a clinical trial with BIA 6-
- •Subjects who had used any investigational drug or participated in any clinical trial within 6 months prior to screening.
- •Subjects who had participated in more than 2 clinical trials within the 12 months prior to screening.
- •Subjects who had donated or received any blood or blood products within the 3 months prior to screening.
- •Subjects who were vegetarians, vegans or have medical dietary restrictions.
- •Subjects who cannot communicate reliably with the investigator.
- •Subjects who were unlikely to co-operate with the requirements of the study.
- •Subjects who were unwilling or unable to give written informed consent.
- •(If female) She was pregnant or breast-feeding.
- •(If female) She was of childbearing potential and she did not use an effective contraceptive method (double-barrier, intra-uterine device or abstinence) or she used oral contraceptives.
研究组 & 干预措施
Group 1: BIA 6-512 25 mg or placebo
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
干预措施: Placebo (Drug)
Group 1: BIA 6-512 25 mg or placebo
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
干预措施: BIA 6-512 (Drug)
Group 1: BIA 6-512 25 mg or placebo
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
干预措施: Madopar® 250 (Drug)
Group 1: BIA 6-512 25 mg or placebo
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
干预措施: Nebicapone (Drug)
Group 2: BIA 6-512 50 mg or placebo
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
干预措施: Placebo (Drug)
Group 2: BIA 6-512 50 mg or placebo
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
干预措施: BIA 6-512 (Drug)
Group 2: BIA 6-512 50 mg or placebo
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
干预措施: Madopar® 250 (Drug)
Group 2: BIA 6-512 50 mg or placebo
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
干预措施: Nebicapone (Drug)
Group 3: BIA 6-512 75 mg or placebo
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
干预措施: Placebo (Drug)
Group 3: BIA 6-512 75 mg or placebo
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
干预措施: BIA 6-512 (Drug)
Group 3: BIA 6-512 75 mg or placebo
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
干预措施: Madopar® 250 (Drug)
Group 3: BIA 6-512 75 mg or placebo
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
干预措施: Nebicapone (Drug)
Group 4: BIA 6-512 100 mg or placebo
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
干预措施: Placebo (Drug)
Group 4: BIA 6-512 100 mg or placebo
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
干预措施: BIA 6-512 (Drug)
Group 4: BIA 6-512 100 mg or placebo
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
干预措施: Madopar® 250 (Drug)
Group 4: BIA 6-512 100 mg or placebo
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
干预措施: Nebicapone (Drug)
结局指标
主要结局
Day 4 - AUC from time zero to 8 h post-dose (AUC0-τ)
时间窗: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose.
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 4
Day 5 - Area under the plasma concentration-time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification (AUC0-t)
时间窗: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 5
Day 5 - AUC from time zero to 8 h post-dose (AUC0-τ)
时间窗: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 5
Day 5 - Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞)
时间窗: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 5
Day 4 - Time of occurrence of Cmax (tmax)
时间窗: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose.
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 4
Day 5 - Maximum observed plasma drug concentration (Cmax)
时间窗: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 5
Day 4 - Apparent terminal elimination half-life, calculated from ln 2/λz (t1/2)
时间窗: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose.
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 4
Day 4 - Area under the plasma concentration-time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification (AUC0-t)
时间窗: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose.
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 4
Day 5 - Time of occurrence of Cmax (tmax)
时间窗: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 5
Day 4 - Maximum observed plasma drug concentration (Cmax)
时间窗: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose.
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 4
Day 4 - Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞)
时间窗: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose.
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 4
Day 5 - Apparent terminal elimination half-life, calculated from ln 2/λz (t1/2)
时间窗: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 5
次要结局
未报告次要终点