effect of bia 6-512 at steady-state on the levodopa pharmacokinetics

Conditions: Parkinson Disease

Summary: 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.

Eligibility criteria:
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.