Pharmacokinetics of BIA 9-1067 in Subjects With Hepatic Impairment

Open-label, Single-dose, Multi-center Study, Investigating the Pharmacokinetics of BIA 9-1067 in Subjects With Hepatic Impairment

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.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: BIA 9-1067

Detailed Description

This was an open-label, single-dose, parallel-group, in-patient, nonrandomized study conducted in 8 patients with moderate chronic hepatic impairment and in 8 healthy matched subjects matched by origin, age, sex, weight, and smoking habits.

Each hepatic impaired patient and matched healthy subject participated in the study for approximately one month, including a 21-day screening period and a 4-day/4-night inpatient period. The inpatient period covered the period from Day -1 to Day 4 morning (through 72 hours after administration). The final study evaluation was performed for all subjects in the morning of the day of discharge, Day 4.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Rennes, France, F-35000
    • Biotrial, 7-9 rue Jean-Louis Bertrand
• Russian Federation
  • Moscow, Russian Federation, 17292
    • City clinical Hospital N°64
  • Moscow, Russian Federation
    • City clinical Hospital N°3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 - Hepatic impaired subjects; Group 1 - subjects with moderate chronic hepatic impairment treated with BIA 9-1067	Drug: BIA 9-1067; Opicapone, OPC; Other Names: Opicapone
Experimental: Group 2 - Healthy subjects; Group 2 - healthy subjects treated with BIA 9-1067	Drug: BIA 9-1067; Opicapone, OPC; Other Names: Opicapone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax - Maximum Plasma Concentration of BIA 9-1067	BIA 9-1067 Cmax following a single dose of 50mg BIA 9-1067	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	BIA 9-1067 Tmax following a single dose of 50mg BIA 9-1067	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
Area Under the Curve (AUC0-t)	BIA 9-1067 AUC0-t following a single dose of 50mg BIA 9-1067	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

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.
• Investigators: Study Director: Patricio Soares-da-Silva, MD, PhD, Bial - Portela & Cª, S.A.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: January 20, 2012
• First Submitted That Met QC Criteria: March 28, 2014
• First Posted (Estimate): April 2, 2014

Study Record Updates

• Last Update Posted (Estimate): January 15, 2015
• Last Update Submitted That Met QC Criteria: January 8, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Opicapone; BIA 9-1067; catechol-O-methyltransferase (COMT)
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antiparkinson Agents; Anti-Dyskinesia Agents; Catechol O-Methyltransferase Inhibitors; Opicapone
• Other Study ID Numbers: BIA-91067-106