Pharmacokinetics of BIA 9-1067 in Subjects With Hepatic Impairment
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease
Intervention: BIA 9-1067
Intervention description: Opicapone, OPC
Intervention MeSH terms: Opicapone
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: BIA 9-1067; Opicapone; catechol-O-methyltransferase (COMT)

Summary:

      The purpose of this study is to assess the pharmacokinetics (PK) of BIA 9-1067 in patients
      with moderate chronic hepatic impairment and in matched healthy subjects.
    

Eligibility criteria:

        Inclusion Criteria:

        All subjects:

          1. Men or non-lactating and non-pregnant women,

          2. Women of non-childbearing potential (WONCBP), expected to be surgically sterile
             (hysterectomy, oophorectomy, or tubal ligation) or postmenopausal for >1 year,

          3. 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,

          4. 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),

          5. Expected to have a high probability for compliance with and completion of the study,
             Hepatic Impaired Patients only:

          6. Aged 18 to 65 years,

          7. Body weight ≥ 50 kg,

          8. 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,

          9. Hepatic impairment should not have been associated to an underlying systemic disease,

         10. 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:

         11. Aged 18 to 65 years,

         12. Body weight ≥ 50 kg,

         13. 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:

          1. Presence or history of any disorder that may prevent the successful completion of the
             study. Allergies and Adverse Drug Reactions

          2. History of multiple and/or severe allergies to drugs or foods or a history of
             anaphylactic reactions.

          3. Known or suspected allergy or other adverse drug reactions to the trial product or
             related products (e.g tolcapone or entacapone).

          4. Positive pregnancy test result (serum Beta-HCG) for women of childbearing potential
             only.

          5. 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.

          6. Involvement in other investigational studies of any type within 30 days of BIA 9-1067
             administration.

          7. Donation of blood within 90 days of study day 1.

          8. 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).

          9. Recent history or presence of any disorder that may interfere with the absorption,
             distribution, metabolism, or excretion of BIA 9-1067 (except hepatic impairment).

         10. Patients with severe encephalopathy.

         11. 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), significant
             abdominal pain, persistent nausea and vomiting, or a worsening of total bilirubin or
             prothrombin time by >50%).

         12. Presence of a hepatocellular carcinoma, or an acute hepatic disease caused by
             infection or drug toxicity.

         13. Presence of surgically created portal-systemic shunt.

         14. Positive serologic finding for human immunodeficiency virus (HIV) antibodies.

         15. Prescription and over-the-counter (OTC) medication doses must be stable for 7 days
             before IMP administration.

             Healthy Matched Subjects only:

         16. History of alcoholism or excessive daily alcohol consumption within the past year.
             Excessive alcohol consumption is regarded as an average weekly intake of more than 14
             units for women and 21 units for men (1 unit of alcohol = 8 to 10 g and is
             approximately equivalent to 1 glass of wine or 250 mL of beer or a standard measure of
             spirits).

         17. Any significant cardiovascular, hepatic, renal, respiratory, gastrointestinal,
             endocrine, immunologic, dermatologic, hematologic, neurologic, or psychiatric disease.

         18. Any clinically important deviation from normal limits in physical examination, vital
             signs, or 12-lead ECGs.

         19. Acute disease state (e.g., nausea, vomiting, fever, diarrhea) within 7 days of study
             day 1.

         20. Positive serologic findings for HIV antibodies, hepatitis B surface antigen (Hbs Ag),
             and/or hepatitis C virus (HCV) antibodies.

         21. Recent history or presence of any disorder that may interfere with the absorption,
             distribution, metabolism, or excretion of BIA 9-1067.

         22. Use of any prescription drug within 30 days of IMP administration.

         23. Use of any OTC drugs including herbal supplements (except for the occasional use of
             acetaminophen and vitamins ≤100% recommended daily allowance) within 14 days of study
             day 1.