Effect of BIA 6-512 at Steady-state on the Levodopa Pharmacokinetics
Effect of BIA 6-512 at Steady-state on the Levodopa Pharmacokinetics
The purpose of the study was to To investigate 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 entacapone 200 mg.
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 (UFHBIAL - Portela & Cª, SA) 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 entacapone 200 mg
 (Comtan®) 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 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.
Inclusion Criteria:

 -  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.

 Exclusion Criteria:

 -  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 6-512.

 -  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.