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Pharmacokinetic Interaction Between BIA 9-1067 and Standard-release Levodopa/Carbidopa

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bial - Portela C S.A.
ClinicalTrials.gov Identifier:
NCT01533077
First received: January 24, 2012
Last updated: June 20, 2012
Last verified: June 2012

January 24, 2012
June 20, 2012
March 2009
October 2009   (final data collection date for primary outcome measure)
maximum observed plasma concentration (Cmax) [ Time Frame: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose. ] [ Designated as safety issue: No ]
Pharmacokinetic parameters
maximum observed plasma concentration (Cmax) [ Time Frame: expected average of 4 days ] [ Designated as safety issue: Yes ]
Pharmacokinetic parameters
Complete list of historical versions of study NCT01533077 on ClinicalTrials.gov Archive Site
  • time of occurrence of Cmax (tmax) [ Time Frame: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose. ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters
  • area under the plasma concentration-time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification (AUC0-t), calculated by the linear trapezoidal rule [ Time Frame: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose. ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters
  • AUC from time zero to infinity (AUC0-∞) [ Time Frame: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose. ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters
  • Maximum observed effect on COMT activity (Emax) [ Time Frame: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose. ] [ Designated as safety issue: No ]
    Pharmacodynamic parameters
  • Time to occurrence of Emax (tEmax) [ Time Frame: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose. ] [ Designated as safety issue: No ]
    Pharmacodynamic parameters
  • Area under the effect-time curve (AUEC) [ Time Frame: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose. ] [ Designated as safety issue: No ]
    Pharmacodynamic parameters
  • Maximum percent inhibition of COMT activity [ Time Frame: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose. ] [ Designated as safety issue: No ]
    Pharmacodynamic parameters
  • Number of Participants with Adverse Events [ Time Frame: throughout the study. ] [ Designated as safety issue: Yes ]
    evaluation of safety: This evaluation will take into account the adverse events recorded and the results of the clinical laboratory safety tests, vital signs, 12-lead ECG and any other relevant parameter.
  • time of occurrence of Cmax (tmax) [ Time Frame: expected average of 4 days ] [ Designated as safety issue: Yes ]
    Pharmacokinetic parameters
  • area under the plasma concentration-time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification (AUC0-t), calculated by the linear trapezoidal rule [ Time Frame: expected average of 4 days ] [ Designated as safety issue: Yes ]
    Pharmacokinetic parameters
  • AUC from time zero to infinity (AUC0-∞), calculated from AUC0-t + (C last/λz) [ Time Frame: expected average of 4 days ] [ Designated as safety issue: Yes ]
    Pharmacokinetic parameters
  • t1/2, calculated from ln 2/λz [ Time Frame: expected average of 4 days ] [ Designated as safety issue: Yes ]
    Pharmacokinetic parameters
  • Maximum observed effect on COMT activity, Emax [ Time Frame: expected average of 4 days ] [ Designated as safety issue: Yes ]
    Pharmacodynamic parameters
  • Time to occurrence of Emax, tEmax [ Time Frame: expected average of 4 days ] [ Designated as safety issue: Yes ]
    Pharmacodynamic parameters
  • Area under the effect-time curve, AUEC [ Time Frame: expected average of 4 days ] [ Designated as safety issue: Yes ]
    Pharmacodynamic parameters
  • Maximum percent inhibition of COMT activity, calculated as [(E0-Emax)/E0]*100, where E0 is the baseline (pre-dose) value [ Time Frame: expected average of 4 days ] [ Designated as safety issue: Yes ]
    Pharmacodynamic parameters
  • Individual and summary blood pressure, heart rate, 12-lead ECG parameters, hematology, and biochemistry tests, and adverse events will be included in the evaluation of safety [ Time Frame: expected average of 4 days ] [ Designated as safety issue: Yes ]
    evaluation of safety
Not Provided
Not Provided
 
Pharmacokinetic Interaction Between BIA 9-1067 and Standard-release Levodopa/Carbidopa
Pharmacokinetic Interaction Between BIA 9-1067 and Standard-release Levodopa/Carbidopa in Healthy Subjects

To investigate the pharmacokinetics of levodopa when administered concomitantly with BIA 9-1067 or 1 hour after.

Single-centre, open-label, randomized, gender-balanced, crossover study with four consecutive single-dose treatment periods.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Parkinson Disease
  • Drug: BIA 9-1067
    50 mg of BIA 9-1067 (single-dose)
  • Drug: levodopa/carbidopa
    immediate-release levodopa/carbidopa 100/25 (single-dose).
  • Experimental: BIA 9-1067
    Intervention: Drug: BIA 9-1067
  • Active Comparator: levodopa/carbidopa
    Intervention: Drug: levodopa/carbidopa
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
18
February 2010
October 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Availability for the entire study period and willingness to adhere to the protocol requirements as evidenced by the informed consent form (ICF) duly read, signed and dated by the volunteer prior to participation in the study.
  • Male or female volunteers.
  • Volunteers of at least 18 years of age but not older than 45 years.
  • Volunteers with body mass index (BMI) greater than or equal to 19 and below 30 kg/m2.
  • Volunteers who were healthy as determined by pre-study (at screening) medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG.
  • Volunteers who had clinical laboratory test results judged clinically acceptable (within the laboratory's stated normal range; if not within this range, they must had been without any clinical significance) at screening and admission to first treatment period.
  • Volunteers who had negative tests for hepatitis B surface antigen (HBsAg), anti-hepatitis C antibodies (HCV Ab), and Human immunodeficiency viruses -1 and -2 antibodies (HIV-1 and HIV-2 Ab) at screening.
  • Volunteers who had negative screen of ethyl alcohol and drugs of abuse at screening.
  • Volunteers who were non- or ex-smokers. For the purpose of this study, an ex-smoker is defined as someone who completely stopped smoking for at least 3 months before day 1 of this study.
  • Due to unknown risks and potential harm to the unborn fetus, sexually active men or women must have agreed to use a medically acceptable form of contraception throughout the study.
  • If female of childbearing potential, she had a negative HCG beta serum pregnancy test at screening and admission to each treatment period
  • The informed consent form must have been signed by all volunteers, prior to their participation in the study.

Exclusion Criteria:

  • Volunteers who did not conform to the above inclusion criteria, or in case of
  • Volunteers who had a clinically relevant surgical history.
  • Volunteers who had a clinically relevant family history.
  • Volunteers who had a history of relevant atopy.
  • Volunteers who had a significant infection or known inflammatory process at screening or admission to the treatment period.
  • Volunteers who had acute gastrointestinal symptoms at the time of screening or admission to the treatment period (e.g., nausea, vomiting, diarrhoea, heartburn).
  • Volunteers who were vegetarians, vegans or have medical dietary restrictions.
  • Volunteers who could not communicate reliably with the investigator.
  • Volunteers who were unlikely to co-operate with the requirements of the study.
  • History of hypersensitivity to BIA 9-1067, tolcapone, entacapone, levodopa, benserazide or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs.
  • Presence of significant gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects.
  • History of significant gastrointestinal, liver or kidney disease that may affect drug bioavailability.
  • Presence or history of significant cardiovascular, pulmonary, hematologic, neurologic, psychiatric, lymphatic, musculoskeletal, genitourinary, endocrine, immunologic, dermatologic or connective tissue disease.
  • Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases.
  • Presence of significant heart disease or disorder according to ECG.
  • Presence of suspicious undiagnosed skin lesions or a history of melanoma.
  • Previous history of Neuroleptic Malignant Syndrome (NMS) and/or nontraumatic rhabdomyolysis.
  • History of significant glaucoma.
  • Used of prescription medications including monoamine oxidase (MAO) inhibitors within 28 days before day 1 of the study.
  • Used of over-the-counter (OTC) products within 7 days before day 1 of the study.
  • Maintenance therapy with any drug, or significant history of drug dependency (drug abuse) or alcohol abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic).
  • Any clinically significant illness in the previous 28 days before day 1 of this study.
  • Volunteers who took an Investigational Product (in another clinical trial) or donated 50 mL or more of blood in the previous 28 days before day 1 of this study.
  • Poor motivation, intellectual problems likely to limit the validity of consent to participate in the study or limit the ability to comply with the protocol requirements or inability to cooperate adequately, inability to understand and to observe the instructions of the physician.
  • Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the previous 56 days before day 1 of this study.
  • Positive urine screening of ethyl alcohol or drugs of abuse at admission to the treatment period.
  • Any history of tuberculosis and/or prophylaxis for tuberculosis.
  • Positive results to HIV, HBsAg or anti-HCV tests.
  • Participation in any previous clinical study with BIA 9-1067 within 84 days before day 1 of the study.
  • Females who were pregnant according to a positive serum pregnancy test or were lactating.
  • Females of childbearing potential who refused to use an acceptable contraceptive regimen throughout the study.
Both
18 Years to 45 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT01533077
BIA-91067-117
No
Bial - Portela C S.A.
Bial - Portela C S.A.
Not Provided
Principal Investigator: Eric Sicard, MD Algorithme Pharma Inc
Bial - Portela C S.A.
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP