A Double-blind, Randomised, Placebo- and Active-controlled Multiple-dose Study of BIA 9-1067 to Investigate Its Effect on Levodopa Pharmacokinetics Following a Levodopa/Carbidopa 100/25 mg Single-dose in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 82
- 试验地点
- 1
- 主要终点
- Cmax - Maximum Plasma Concentration of Levodopa
研究概览
简要总结
To investigate the effect of repeated dosing of BIA 9-1067 on the levodopa pharmacokinetics, in comparison to placebo and entacapone.
详细描述
Single-centre, double-blind, randomised, parallel-group study in 80 young male and female healthy subjects.
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
- •Able and willing to give written informed consent.
- •Male or female subjects aged between 18 and 45 years, inclusive.
- •Subjects of body mass index (BMI) between 19 and 30 kg/m2, inclusive.
- •Healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG.
- •Negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab at screening.
- •Clinical laboratory test results clinically acceptable at screening and admission to the treatment period.
- •Negative screen for alcohol and drugs of abuse at screening and admission to the treatment period.
- •Non-smokers or ex-smokers for at least 3 months.
- •(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: intrauterine device (by the subject) and condoms (by the partner) or diaphragm (by the subject) and condoms (by the partner) or spermicide (by the subject) and condoms (by the partner).
- •(If female) She had a negative urine pregnancy test at screening and admission to the treatment period.
排除标准
- •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.
- •Any abnormality in the coagulation tests.
- •Any abnormality in the liver function tests.
- •A history of relevant atopy or drug hypersensitivity.
- •A history or presence of narrow-angle glaucoma.
- •A suspicious undiagnosed skin lesions or a history of melanoma.
- •History of alcoholism or drug abuse.
- •Consumed more than 14 units of alcohol a week.
- •Significant infection or known inflammatory process at screening or admission to the treatment period.
- •Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to the treatment period.
- •Had used non-selective monoamine oxidase (MAO) inhibitors within 2 weeks of admission to the treatment period.
- •Had used medicines within 2 weeks of admission to the treatment period that may have affected the safety or other study assessments, in the investigator's opinion.
- •Had previously received BIA 9-
- •Had used any investigational drug or participated in any clinical trial within 6 months prior to screening.
- •Had participated in more than 2 clinical trials within the 12 months prior to screening.
- •Had donated or received any blood or blood products within the 3 months prior to screening.
- •Vegetarians, vegans or had medical dietary restrictions.
- •Cannot communicate reliably with the investigator.
- •Unlikely to co-operate with the requirements of the study.
- •Unwilling or unable to gave written informed consent.
- •(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.
研究组 & 干预措施
Group 2
Day 1 to 7:
BIA 9-1067 5 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose
Day 8:
BIA 9-1067 5 mg: 7 AM dose Placebo+ levodopa/carbidopa 100/25 mg: 8 AM dose
干预措施: levodopa/carbidopa (Drug)
Group 1
Placebo at all the dosing times
干预措施: Placebo (Drug)
Group 2
Day 1 to 7:
BIA 9-1067 5 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose
Day 8:
BIA 9-1067 5 mg: 7 AM dose Placebo+ levodopa/carbidopa 100/25 mg: 8 AM dose
干预措施: BIA 9-1067 5 mg (Drug)
Group 2
Day 1 to 7:
BIA 9-1067 5 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose
Day 8:
BIA 9-1067 5 mg: 7 AM dose Placebo+ levodopa/carbidopa 100/25 mg: 8 AM dose
干预措施: Placebo (Drug)
Group 3
Day 1 to 7:
BIA 9-1067 15 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose
Day 8:
BIA 9-1067 15 mg: 7 AM dose Placebo+ levodopa/carbidopa 100/25 mg: 8 AM dose
干预措施: Placebo (Drug)
Group 3
Day 1 to 7:
BIA 9-1067 15 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose
Day 8:
BIA 9-1067 15 mg: 7 AM dose Placebo+ levodopa/carbidopa 100/25 mg: 8 AM dose
干预措施: levodopa/carbidopa (Drug)
Group 3
Day 1 to 7:
BIA 9-1067 15 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose
Day 8:
BIA 9-1067 15 mg: 7 AM dose Placebo+ levodopa/carbidopa 100/25 mg: 8 AM dose
干预措施: BIA 9-1067 15 mg (Drug)
Group 4
Day 1 to 7:
BIA 9-1067 30 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose
Day 8:
BIA 9-1067 30 mg: 7 AM dose Placebo + levodopa/carbidopa 100/25 mg: 8 AM dose
干预措施: Placebo (Drug)
Group 4
Day 1 to 7:
BIA 9-1067 30 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose
Day 8:
BIA 9-1067 30 mg: 7 AM dose Placebo + levodopa/carbidopa 100/25 mg: 8 AM dose
干预措施: levodopa/carbidopa (Drug)
Group 4
Day 1 to 7:
BIA 9-1067 30 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose
Day 8:
BIA 9-1067 30 mg: 7 AM dose Placebo + levodopa/carbidopa 100/25 mg: 8 AM dose
干预措施: BIA 9-1067 30 mg (Drug)
Group 5
Day 1 to 7:
Placebo: 7 AM dose; Entacapone 200 mg: 8 AM; 4 PM; 12 PM dose
Day 8:
Placebo: 7 AM dose Entacapone 200 mg + levodopa/carbidopa 100/25 mg: 8 AM dose
干预措施: Entacapone (Drug)
Group 5
Day 1 to 7:
Placebo: 7 AM dose; Entacapone 200 mg: 8 AM; 4 PM; 12 PM dose
Day 8:
Placebo: 7 AM dose Entacapone 200 mg + levodopa/carbidopa 100/25 mg: 8 AM dose
干预措施: Placebo (Drug)
Group 5
Day 1 to 7:
Placebo: 7 AM dose; Entacapone 200 mg: 8 AM; 4 PM; 12 PM dose
Day 8:
Placebo: 7 AM dose Entacapone 200 mg + levodopa/carbidopa 100/25 mg: 8 AM dose
干预措施: levodopa/carbidopa (Drug)
结局指标
主要结局
Cmax - Maximum Plasma Concentration of Levodopa
时间窗: 8 days
Cmax - Maximum plasma concentration of levodopa following a single oral administration of Sinemet® 100/25 on Day 8, and 5 mg, 15 mg and 30 mg BIA 9-1067 once-daily (QD), 200 mg entacapone thrice-daily (TID), and placebo, for 8 days
次要结局
- Tmax - Time to Reach Maximum Plasma Concentration of Levodopa(8 days)
- AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification.(8 days)
- AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity(8 days)