Pharmacokinetics of BIA 9-1067 in Subjects With Hepatic Impairment

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT02101190
• Date of registration: 20/01/2012
• Prospective Registration: No
• Primary sponsor: Bial - Portela C S.A.
• Public title: Pharmacokinetics of BIA 9-1067 in Subjects With Hepatic Impairment
• Scientific title: Open-label, Single-dose, Multi-center Study, Investigating the Pharmacokinetics of BIA 9-1067 in Subjects With Hepatic Impairment
• Date of first enrolment: March 2010
• Target sample size: 16
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02101190
• Study type: Interventional
• Phase: Phase 1

Countries of recruitment

France, Russian Federation

Contacts

• Name: Patricio Soares-da-Silva, MD, PhD
• Affiliation: BIAL - Portela & Cª, S.A.

Key inclusion & exclusion 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 [ß-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.



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Parkinson's Disease

Intervention(s)

Drug: BIA 9-1067

Primary Outcome(s)

Area Under the Curve (AUC0-t) [Time Frame: pre-dose (within 1 hour before dose administration) and then at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 hours post-dose]

Cmax - Maximum Plasma Concentration of BIA 9-1067 [Time Frame: pre-dose (within 1 hour before dose administration) and then at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 hours post-dose]

Tmax - Time to Reach Cmax [Time Frame: pre-dose (within 1 hour before dose administration) and then at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 hours post-dose]

Secondary ID(s)

BIA-91067-106

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 15/01/2015
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02101190