Study of BIA 9-1067 to Investigate Its Effect on Levodopa Pharmacokinetic

• pharmacokinetics [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
  To investigate the effect of repeated dosing of BIA 9-1067 (5 mg, 15 mg and 30 mg; once-daily) on the 3-O-methyldopa (3-OMD) pharmacokinetics, in comparison to placebo and entacapone (200 mg; thrice-daily)
• pharmacokinetics [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
  To investigate the effect of repeated dosing of BIA 9-1067 (5 mg, 15 mg and 30 mg; once-daily) on the carbidopa pharmacokinetics, in comparison to placebo and entacapone (200 mg; thrice-daily);
• erythrocyte soluble catechol-O-methyltransferase (S-COMT) activity [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
  To investigate the effect of repeated dosing of BIA 9-1067 (5 mg, 15 mg and 30 mg; once-daily) on erythrocyte soluble catechol-O-methyltransferase (S-COMT) activity, in comparison with placebo and entacapone 200 mg (thrice-daily), in healthy subjects
• pharmacokinetics [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
  To investigate the pharmacokinetics of BIA 9-1067 following repeated dosing (5 mg, 15 mg and 30 mg; once-daily) in healthy subjects
• tolerability and safety [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
  To investigate the tolerability and safety of repeated dosing of BIA 9-1067 (5 mg, 15 mg and 30 mg; once-daily), in comparison with placebo and entacapone (200 mg; thrice-daily), in healthy subjects.

To investigate the effect of repeated dosing of BIA 9-1067 on the levodopa pharmacokinetics, in comparison to placebo and entacapone.

Single-centre, double-blind, randomised, parallel-group study in 80 young male and female healthy subjects.

• Drug: BIA 9-1067
  5 mg, 15 mg, and 30 mg of BIA 9-1067 (once-daily)
• Drug: entacapone
  200 mg entacapone (thrice-daily)
• Drug: Placebo
  placebo (four times a day)
• Drug: levodopa/carbidopa
  standard release levodopa/carbidopa 100/25 mg (single-dose)

• Experimental: BIA 9-1067
  Intervention: Drug: BIA 9-1067
• Active Comparator: entacapone
  Intervention: Drug: entacapone
• Placebo Comparator: placebo
  Intervention: Drug: Placebo
• Active Comparator: levodopa/carbidopa
  Intervention: Drug: levodopa/carbidopa

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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 9-1067.
• 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.