Pharmacokinetics of BIA 9-1067 in Subjects With Hepatic Impairment

Inclusion Criteria

All subjects:

• Men or non-lactating and non-pregnant women,
• Women of non-childbearing potential (WONCBP), expected to be surgically sterile (hysterectomy, oophorectomy, or tubal ligation) or postmenopausal for >1 year,
• Women of childbearing potential (WOCBP), expected to be using an acceptable method of contraception (sexual abstinence, implants, IUD, injectables, vasectomised partner or association of condom + spermicide, diaphragm + spermicide, diaphragm + condom) for a period of at least 1 month before and after dose administration. WOCBP were expected to have a negative pregnancy test (serum beta-human chorionic gonadotropin [β-HCG]) result within 48 hours before the start of the first IMP administration. Hormonal contraceptives were not allowed because the effect of BIA 9-1067 on the metabolism of oral contraceptives and vice versa is not yet known,
• Male subjects should not have been planning to father a child or donate sperm, during the study and 1 month after the end of the study. Acceptable methods of contraception comprised condom and a medically accepted contraceptive method for the female partner (intra-uterine device with spermicide, hormonal contraceptive for the last 2 months),
• Expected to have a high probability for compliance with and completion of the study, Hepatic Impaired Patients only:
• Aged 18 to 65 years,
• Body weight ≥ 50 kg,
• Child Pugh class B (score at 7, 8 or 9) calculated according to the Child-Pugh classification based on history, physical examination, and laboratory test results at screening and on Day -1,
• Hepatic impairment should not have been associated to an underlying systemic disease,
• Medications necessary for the management of the hepatic disease or concomitant conditions were permitted if the therapeutic regimen has been stable for at least 7 days before BIA 9-1067 administration and if they did not interfere with the kinetics of the tested product,

Matched Healthy Subjects only:

• Aged 18 to 65 years,
• Body weight ≥ 50 kg,
• Healthy as determined by the investigator on the basis of medical history, physical examination, clinical laboratory test results, vital signs, and 12-lead electrocardiogram (ECG). Alanine aminotransferase (ALT) and creatinine levels should have been strictly within the normal range for eligibility.

Exclusion Criteria

• Presence or history of any disorder that may prevent the successful completion of the study. Allergies and Adverse Drug Reactions
• History of multiple and/or severe allergies to drugs or foods or a history of anaphylactic reactions.
• Known or suspected allergy or other adverse drug reactions to the trial product or related products (e.g tolcapone or entacapone).
• Positive pregnancy test result (serum Beta-HCG) for women of childbearing potential only.
• Consumption of any caffeine-containing products (eg, coffee, tea, chocolate, or cola), grapefruit, grapefruit-containing products, or alcoholic beverages from 48 hours before study day 1 until the end of the inpatient confinement period.
• Involvement in other investigational studies of any type within 30 days of BIA 9-1067 administration.
• Donation of blood within 90 days of study day 1.
• Evidence of unstable clinically significant disease other than impaired hepatic function (e.g., cardiovascular, cerebrovascular, respiratory, renal disease, or any serious disorder that currently requires a physician's care).
• Recent history or presence of any disorder that may interfere with the absorption, distribution, metabolism, or excretion of BIA 9-1067 (except hepatic impairment).
• Patients with severe encephalopathy.
• Acute exacerbation of hepatic disease, as indicated by worsening of clinical and/or laboratory signs of hepatic impairment, within the 2 weeks before BIA 9-1067 administration (eg, advanced ascites, infection of ascites, fever, hepatic encephalopathy or active gastrointestinal bleeding (hematemesis, melena), signif