Effect of BIA 9-1067 on the Pharmacokinetics of Repaglinide

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bial - Portela C S.A.
ClinicalTrials.gov Identifier:
NCT01536366
First received: January 23, 2012
Last updated: June 20, 2012
Last verified: June 2012
  Purpose

The purpose of this study is to investigate the CYP2C8 inhibition by BIA 9-1067.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of BIA 9-1067 on the Pharmacokinetics of Repaglinide in Healthy Volunteers

Resource links provided by NLM:


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

Primary Outcome Measures:
  • maximum observed plasma concentration (Cmax) [ Time Frame: pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose. ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters to investigate CYP2C8 inhibition by BIA 9-1067 through the assessment of its effect on the pharmacokinetics of repaglinide, a substrate of CYP2C8.


Secondary Outcome Measures:
  • time of occurrence of Cmax (tmax) [ Time Frame: pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose. ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters to investigate CYP2C8 inhibition by BIA 9-1067 through the assessment of its effect on the pharmacokinetics of repaglinide, a substrate of CYP2C8.

  • area under the plasma concentration-time curve (AUC) [ Time Frame: pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose. ] [ Designated as safety issue: No ]
    area under the plasma concentration-time curve (AUC) from time zero to the last sampling time at which the drug concentration was at or above the lower limit of quantification (AUC0-t), calculated by the linear trapezoidal rule is a Pharmacokinetic parameters to investigate CYP2C8 inhibition by BIA 9-1067 through the assessment of its effect on the pharmacokinetics of repaglinide, a substrate of CYP2C8.

  • AUC from time zero to infinity (AUC0-∞) [ Time Frame: pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose. ] [ Designated as safety issue: No ]
    AUC from time zero to infinity (AUC0-∞), calculated from AUC0-t + (Clast/λz), where Clast is the last quantifiable concentration and λz the apparent terminal rate constant calculated by loglinear regression of the terminal segment of the drug plasma concentration versus time curve as a Pharmacokinetic parameters to investigate CYP2C8 inhibition by BIA 9-1067 through the assessment of its effect on the pharmacokinetics of repaglinide, a substrate of CYP2C8.

  • apparent terminal half-life (t½), calculated from ln 2/λz [ Time Frame: pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose. ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters to investigate CYP2C8 inhibition by BIA 9-1067 through the assessment of its effect on the pharmacokinetics of repaglinide, a substrate of CYP2C8.

  • apparent total body clearance (CL/F) [ Time Frame: pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose. ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters to investigate CYP2C8 inhibition by BIA 9-1067 through the assessment of its effect on the pharmacokinetics of repaglinide, a substrate of CYP2C8.

  • apparent volume of distribution (V/F) [ Time Frame: pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose. ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters to investigate CYP2C8 inhibition by BIA 9-1067 through the assessment of its effect on the pharmacokinetics of repaglinide, a substrate of CYP2C8

  • pulse rate & blood pressure [ Time Frame: Screening, admission, pre-dose, 1, 2, 4, 8, 12, 24 h post-dose and follow-up ] [ Designated as safety issue: Yes ]
    Evaluation of safety

  • 12-lead ECG parameters [ Time Frame: Screening, admission, 24 h post-dose and follow-up ] [ Designated as safety issue: Yes ]
    Evaluation of safety

  • haematology [ Time Frame: Screening, admission, 24 h post-dose and follow-up ] [ Designated as safety issue: Yes ]
    Evaluation of safety

  • plasma biochemistry tests [ Time Frame: Screening, admission, 24 h post-dose and follow-up ] [ Designated as safety issue: Yes ]
    Evaluation of safety

  • Number of adverse events/patient [ Time Frame: throughout the entire study period ] [ Designated as safety issue: Yes ]
    Evaluation of safety: All clinical adverse events will be monitored throughout the entire study period.


Enrollment: 28
Study Start Date: June 2009
Study Completion Date: January 2011
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIA 9-1067 Drug: BIA 9-1067
25 mg BIA 9-1067 (single-dose)
Active Comparator: repaglinide Drug: repaglinide
0.5 mg repaglinide (single-dose)

Detailed Description:

Single-centre, open-label, randomised, two-way crossover study in healthy young male and female volunteers

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Able and willing to give written informed consent.
  • Male or female subjects aged between 18 and 45 years, inclusive.
  • Subjects of body mass index (BMI) between 19 and 30 kg/m2, inclusive.
  • Healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG.
  • Negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab at screening.
  • Clinical laboratory test results clinically acceptable at screening and admission to each treatment period.
  • Negative screen for alcohol and drugs of abuse at screening and admission to each treatment period.
  • Non-smokers or ex-smokers for at least 3 months.
  • (If female) She was not of childbearing potential by reason of surgery or, if of childbearing potential, she used one of the following methods of contraception: double barrier or intrauterine device.
  • (If female) She had a negative urine pregnancy test at screening and admission to each treatment period.

Exclusion Criteria:

  • Clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders.
  • Clinically relevant surgical history.
  • Any abnormality in the coagulation tests.
  • Any abnormality in the liver function tests.
  • A history of relevant atopy or drug hypersensitivity.
  • History of alcoholism or drug abuse.
  • Consumed more than 14 units of alcohol a week.
  • Significant infection or known inflammatory process at screening or admission to each treatment period.
  • Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to each treatment period.
  • Had used medicines within 2 weeks of admission to first period that may have affected the safety or other study assessments, in the investigator's opinion.
  • Had previously received BIA 9-1067.
  • Had used any investigational drug or participated in any clinical trial within 6 months prior to screening.
  • Had participated in more than 2 clinical trials within the 12 months prior to screening.
  • Had donated or received any blood or blood products within the 3 months prior to screening.
  • Vegetarians, vegans or had medical dietary restrictions.
  • Cannot communicate reliably with the investigator.
  • Unlikely to co-operate with the requirements of the study.
  • Unwilling or unable to gave written informed consent.
  • Employees at BIAL - Portela & Cª, S.A.
  • (If female) She was pregnant or breast-feeding.
  • (If female) She was of childbearing potential and she did not used an approved effective contraceptive method (double-barrier or intra-uterine device) or she used oral contraceptives.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01536366

Locations
Portugal
Bial - Portela & Cª, S.A.
S. Mamede do Coronado, Portugal, 4745-457
Sponsors and Collaborators
Bial - Portela C S.A.
Investigators
Principal Investigator: Manuel Vaz-da-Silva, MD, PhD BIAL - Portela & Cª S.A.
  More Information

No publications provided

Responsible Party: Bial - Portela C S.A.
ClinicalTrials.gov Identifier: NCT01536366     History of Changes
Other Study ID Numbers: BIA-91067-115
Study First Received: January 23, 2012
Last Updated: June 20, 2012
Health Authority: Portugal: National Pharmacy and Medicines Institute

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
Repaglinide
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 21, 2014