Effect of BIA 9-1067 at Steady-state on the Pharmacokinetics of Levodopa/Carbidopa and Levodopa/Benserazide

Inclusion Criteria

• Availability for the entire study period and willingness to adhere to the protocol requirements as evidenced by the informed consent form (ICF) duly read, signed and dated by the volunteer prior to participation in the study.
• Male or female volunteers.
• Volunteers of at least 25 years of age but not older than 45 years.
• Volunteers with body mass index (BMI) greater than or equal to 19 and below 30 kg/m2.
• Volunteers who were healthy as determined by pre-study (at screening) medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG.
• Volunteers who had clinical laboratory test results judged clinically acceptable (within the laboratory's stated normal range; if not within this range, they must had been without any clinical significance) at screening and admission to first treatment period.
• Volunteers who had negative tests for hepatitis B surface antigen (HBsAg), anti-hepatitis C antibodies (HCV Ab), and Human immunodeficiency viruses -1 and -2 antibodies (HIV-1 and HIV-2 Ab) at screening.
• Volunteers who had negative screen of ethyl alcohol and drugs of abuse at screening and admission to the treatment period.
• Volunteers who were non- or ex-smokers. For the purpose of this study, an ex-smoker is defined as someone who completely stopped smoking for at least 3 months before day 1 of this study.
• Due to unknown risks and potential harm to the unborn fetus, sexually active men or women must have agreed to use a medically acceptable form of contraception throughout the study.
• If female of childbearing potential, she had a negative HCG beta serum pregnancy test at screening and admission to each treatment period.
• The informed consent form must have been signed by all volunteers, prior to their participation in the study.

Exclusion Criteria

• Volunteers who did not conform to the above inclusion criteria, or in case of
• Volunteers who had a clinically relevant surgical history.
• Volunteers who had a clinically relevant family history.
• Volunteers who had a history of relevant atopy.
• Volunteers who had a significant infection or known inflammatory process at screening or admission to the treatment period.
• Volunteers who had acute gastrointestinal symptoms at the time of screening or admission to the treatment period (e.g., nausea, vomiting, diarrhoea, heartburn).
• Volunteers who were vegetarians, vegans or have medical dietary restrictions.
• Volunteers who could not communicate reliably with the investigator.
• Volunteers who were unlikely to co-operate with the requirements of the study.
• History of hypersensitivity to BIA 9-1067, tolcapone, entacapone, levodopa, benserazide or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs.
• Presence of significant gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects.
• History of significant gastrointestinal, liver or kidney disease that may affect drug bioavailability.
• Presence or history of significant cardiovascular, pulmonary, hematologic, neurologic, psychiatric, lymphatic, musculoskeletal, genitourinary, endocrine, immunologic, dermatologic or connective tissue disease.
• Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases.
• Presence of significant heart disease or disorder according to ECG.
• Presence of suspicious undiagnosed skin lesions or a history of melanoma.
• Previous history of Neuroleptic Malignant Syndrome (NMS) and/or nontraumatic rhabdomyolysis.
• History of significant glaucoma.
• Used of prescription medications including monoamine oxidase (MAO) inhibitors within 28 days before day 1 of the study.
• Used of over-the-counter (OTC) products within 7 days before day