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Pharmacokinetics of BIA 9-1067 in Healthy Japanese and Caucasian Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bial - Portela C S.A.
ClinicalTrials.gov Identifier:
NCT01520987
First received: January 26, 2012
Last updated: May 12, 2016
Last verified: May 2016
  Purpose
To assess the pharmacokinetics of BIA 9-1067 in healthy Japanese subjects

Condition Intervention Phase
Parkinson Disease
Drug: BIA 9-1067
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Randomized, Double-Blinded, Placebo-Controlled, Multiple Ascending Dose Study to Compare the Pharmacokinetics of BIA 9-1067 in Healthy Japanese and Caucasian Subjects

Resource links provided by NLM:


Further study details as provided by Bial - Portela C S.A.:

Primary Outcome Measures:
  • Cmax of BIA 9-1067 - Maximum Observed Plasma Concentration of BIA 9-1067 (Day 1) [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]
    Cmax - maximum observed plasma concentration following single (Day 1) oral administrations of 5, 25 and 50 mg OPC in healthy Japanese and matched healthy Caucasian subjects Blood samples collected for PK analysis at the following timepoints: on Day 1 at pre-dose (within 1 hour before dose administration) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours post-dose.

  • Cmax of BIA 9-1067 - Maximum Observed Plasma Concentration of BIA 9-1067 (Day 10) [ Time Frame: Day 10 ] [ Designated as safety issue: Yes ]

    Cmax - maximum observed plasma concentration following Last (Day 10) oral administrations of 5, 25 and 50 mg OPC in healthy Japanese and matched healthy Caucasian subjects.

    Blood samples collected for PK analysis at the following timepoints: Day 10 at pre-dose (within 1 hour before dose administration) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose


  • AUC0-t - Area Under the Concentration-time Curve (AUC) From Time Zero to Last Time Point With Concentrations Above the Lower Limit of Quantitation of BIA 9-1067 (Day 1) [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]

    AUC0-t - area under the concentration-time curve (AUC) from time zero to last time point with concentrations above the lower limit of quantitation of BIA 9-1067 following single (Day 1) oral administrations of 5, 25 and 50 mg OPC in healthy Japanese and matched healthy Caucasian subjects.

    Blood samples collected for PK analysis at the following timepoints: on Day 1 at pre-dose (within 1 hour before dose administration) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours post-dose.


  • AUC0-t - Area Under the Concentration-time Curve (AUC) From Time Zero to Last Time Point With Concentrations Above the Lower Limit of Quantitation of BIA 9-1067 (Day 10) [ Time Frame: Day 10 ] [ Designated as safety issue: Yes ]

    AUC0-t - Area Under the Concentration-time Curve (AUC) From Time Zero to Last Time Point With Concentrations Above the Lower Limit of Quantitation of BIA 9-1067 following Last (Day 10) oral administrations of 5, 25 and 50 mg OPC in healthy Japanese and matched healthy Caucasian subjects.

    Blood samples collected for PK analysis at the following timepoints: Day 10 at pre-dose (within 1 hour before dose administration) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose


  • AUC0-∞ - Area Under the Concentration of BIA 9-1067-time Curve (AUC) From Time Zero to Infinity (Day 1) [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]
    AUC0-∞ - area under the concentration of BIA 9-1067-time curve (AUC) from time zero to infinity following single (Day 1) oral administrations of 5, 25 and 50 mg OPC in healthy Japanese and matched healthy Caucasian subjects Blood samples collected for PK analysis at the following timepoints: on Day 1 at pre-dose (within 1 hour before dose administration) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours post-dose

  • AUC0-∞ - Area Under the Concentration of BIA 9-1067-time Curve (AUC) From Time Zero to Infinity (Day 10) [ Time Frame: Day 10 ] [ Designated as safety issue: Yes ]

    AUC0-∞ - Area Under the Concentration of BIA 9-1067-time Curve (AUC) From Time Zero to Infinity following Last (Day 10) oral administrations of 5, 25 and 50 mg OPC in healthy Japanese and matched healthy Caucasian subjects.

    Blood samples collected for PK analysis at the following timepoints: Day 10 at pre-dose (within 1 hour before dose administration) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose


  • Tmax of BIA 9-1067 - Time Taken to Reach Maximum Observed Plasma Concentration of BIA 9-1067 (Day 1) [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]

    Tmax of BIA 9-1067 - time taken to reach maximum observed plasma concentration following single (Day 1) oral administrations of 5, 25 and 50 mg OPC in healthy Japanese and matched healthy Caucasian subjects.

    Blood samples collected for PK analysis at the following timepoints: on Day 1 at pre-dose (within 1 hour before dose administration) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours post-dose


  • Tmax of BIA 9-1067 - Time Taken to Reach Maximum Observed Plasma Concentration of BIA 9-1067 (Day 10) [ Time Frame: Day 10 ] [ Designated as safety issue: Yes ]

    Tmax of BIA 9-1067 - Time Taken to Reach Maximum Observed Plasma Concentration of BIA 9-1067 following Last (Day 10) oral administrations of 5, 25 and 50 mg OPC in healthy Japanese and matched healthy Caucasian subjects.

    Blood samples collected for PK analysis at the following timepoints: Day 10 at pre-dose (within 1 hour before dose administration) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose



Enrollment: 105
Study Start Date: May 2011
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Caucasian 5 mg OPC
OPC, opicapone, BIA 9-1067
Drug: BIA 9-1067
5 mg, 25 mg, and 50 mg of BIA 9-1067 (once-daily).
Experimental: Caucasian 25 mg OPC
OPC, opicapone, BIA 9-1067
Drug: BIA 9-1067
5 mg, 25 mg, and 50 mg of BIA 9-1067 (once-daily).
Experimental: Caucasian 50 mg OPC
OPC, opicapone, BIA 9-1067
Drug: BIA 9-1067
5 mg, 25 mg, and 50 mg of BIA 9-1067 (once-daily).
Placebo Comparator: Caucasian Placebo
Placebo, PLC
Drug: Placebo
once-daily
Experimental: Japanese 5 mg OPC
OPC, opicapone, BIA 9-1067
Drug: BIA 9-1067
5 mg, 25 mg, and 50 mg of BIA 9-1067 (once-daily).
Experimental: Japanese 25 mg OPC
OPC, opicapone, BIA 9-1067
Drug: BIA 9-1067
5 mg, 25 mg, and 50 mg of BIA 9-1067 (once-daily).
Experimental: Japanese 50 mg OPC
OPC, opicapone, BIA 9-1067
Drug: BIA 9-1067
5 mg, 25 mg, and 50 mg of BIA 9-1067 (once-daily).
Placebo Comparator: Japanese Placebo
Placebo, PLC
Drug: Placebo
once-daily

Detailed Description:
Randomized, double-blind, placebo-controlled, multiple ascending dose, parallel-group, pharmacokinetic (PK) and pharmacodynamic (PD) study
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Men or nonlactating and nonpregnant women;
  • Caucasian or Japanese subjects. Caucasian subjects are subjects of European descent; Japanese subjects must be first or second generation. Generations will be defined as follows:

    1. First generation Japanese are subjects who may be living outside Japan but were born in Japan to parents of Japanese descent.
    2. Second generation Japanese are subjects who were born outside of Japan to first generation Japanese parents.
  • Aged 18 to 65 years;
  • Body weight ≥50 kg;
  • Within BMI range 18.5 to 30 kg/m2, inclusive;
  • Healthy, as determined by the Investigator on the basis of medical history, physical examination, clinical laboratory test results, vital signs, and 12-lead ECG. Creatinine and ALT levels must be strictly within the normal range for eligibility at Check-in;
  • Women of nonchildbearing potential must be surgically sterile (hysterectomy, oophorectomy, or tubal ligation) or postmenopausal for ≥1 year;
  • Women of childbearing potential must be using an effective nonhormonal method of contraception (intrauterine device or intrauterine system; condom or occlusive cap [diaphragm or cervical or vault caps] with spermicidal foam or gel or film or cream or suppository; true abstinence; or vasectomized male partner, provided that he is the sole partner of that subject) for a period of at least 1 month before and after dose administration. Women of childbearing potential must have a negative pregnancy test result within 48 hours before the start of the first investigational medicinal product (IMP) administration. Hormonal contraceptives will not be allowed because the effect of BIA 9 1067 on the metabolism of hormonal contraceptives and vice versa is not yet known;
  • Nonsmokers, defined as having smoked ≤10 cigarettes per week for the 3 months prior to dosing, abstained from smoking for 7 days prior to Check-in, and having a negative cotinine level ≤500 ng/mL at Check-in;
  • Have a high probability for compliance with and completion of the study, in the opinion of the Investigator;
  • Able to comprehend and willing to sign an ICF.

Exclusion Criteria:

  • Presence or history of any disorder that may prevent the successful completion of the study;
  • 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 (eg, tolcapone or entacapone);
  • 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);
  • Any significant cardiovascular, hepatic, renal, respiratory, gastrointestinal, endocrine, immunologic, dermatologic, hematologic, neurologic, or psychiatric disease, as judged by the Investigator or Sponsor's Medical Monitor;
  • Any clinically important deviation from normal limits in physical examination, vital signs, or 12-lead ECGs, as judged by the Investigator or Sponsor's Medical Monitor;
  • Acute disease state (eg, nausea, vomiting, fever, diarrhea) within 7 days of Study Day 1;
  • Positive serologic findings for HIV antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus antibodies (anti-HCV);
  • Positive screen for drugs of abuse and alcohol;
  • Recent history or presence of any disorder that may interfere with the absorption, distribution, metabolism, or excretion of BIA 9 1067;
  • Positive pregnancy test result for WOCBP 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 Discharge (Day 16);
  • 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;
  • Use of any prescription drug within 30 days of IMP administration unless deemed acceptable by the Principal Investigator (PI) and Medical Monitor;
  • Use of any over-the-counter drugs including herbal supplements (except for the occasional use of acetaminophen and vitamins ≤100% recommended daily allowance) within 14 days of Study Day 1 unless deemed acceptable by the PI and Medical Monitor.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01520987

Locations
United States, Hawaii
Covance Clinical Research Unit, Inc.
Honolulu, Hawaii, United States, 96813
Sponsors and Collaborators
Bial - Portela C S.A.
Investigators
Principal Investigator: Haejung Marr, MD Covance
  More Information

Responsible Party: Bial - Portela C S.A.
ClinicalTrials.gov Identifier: NCT01520987     History of Changes
Other Study ID Numbers: BIA-91067-126 
Study First Received: January 26, 2012
Results First Received: July 22, 2015
Last Updated: May 12, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Bial - Portela C S.A.:
Parkinson Disease
BIA 9-1067

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Opicapone
Catechol O-Methyltransferase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antiparkinson Agents
Anti-Dyskinesia Agents

ClinicalTrials.gov processed this record on September 23, 2016