Pharmacokinetics of BIA 9-1067 in Subjects With Hepatic Impairment

NCT02101190 | Completed Phase 1 Results

• 1 other identifier: BIA-91067-106
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 3

Brief 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.

Conditions

Parkinson's Disease

Keywords

BIA 9-1067; Opicapone; catechol-O-methyltransferase (COMT)

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (2)

Group 1 - Hepatic impaired subjects

EXPERIMENTAL

Group 1 - subjects with moderate chronic hepatic impairment treated with BIA 9-1067

Drug: BIA 9-1067

Group 2 - Healthy subjects

EXPERIMENTAL

Group 2 - healthy subjects treated with BIA 9-1067

Drug: BIA 9-1067

Interventions

BIA 9-1067 DRUG

Opicapone, OPC

Also known as: Opicapone

Group 1 - Hepatic impaired subjects; Group 2 - Healthy subjects

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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), significant abdominal pain, persistent nausea and vomiting, or a worsening of total bilirubin or prothrombin time by \>50%).
• Presence of a hepatocellular carcinoma, or an acute hepatic disease caused by infection or drug toxicity.
• Presence of surgically created portal-systemic shunt.
• Positive serologic finding for human immunodeficiency virus (HIV) antibodies.
• Prescription and over-the-counter (OTC) medication doses must be stable for 7 days before IMP administration.

Sponsors & Collaborators

• Bial - Portela C S.A.: lead

Study Sites (3)

Biotrial, 7-9 rue Jean-Louis Bertrand

Rennes, F-35000, France

Location

City clinical Hospital N°64

Moscow, Moscow, 17292, Russia

Location

City clinical Hospital N°3

Moscow, Moscow, Russia

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

opicapone

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Results Point of Contact

• Title: Head of Clinical Research
• Organization: Bial - Portela & Cª, S.A.

jose.rocha@bial.com

+351 229 866 100

Study Officials

• Patricio Soares-da-Silva, MD, PhD

  BIAL - Portela & Cª, S.A.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2012
• First Posted: April 2, 2014
• Study Start: March 1, 2010
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: January 15, 2015
• Results First Posted: January 15, 2015

Record last verified: 2015-01

Locations

FR (1); RU (2)