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
  Purpose

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


Condition Intervention Phase
Parkinson Disease
Drug: BIA 9-1067
Drug: levodopa/carbidopa
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: Pharmacokinetic Interaction Between BIA 9-1067 and Standard-release Levodopa/Carbidopa in Healthy Subjects

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, 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


Secondary Outcome Measures:
  • 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.


Enrollment: 18
Study Start Date: March 2009
Study Completion Date: February 2010
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIA 9-1067 Drug: BIA 9-1067
50 mg of BIA 9-1067 (single-dose)
Active Comparator: levodopa/carbidopa Drug: levodopa/carbidopa
immediate-release levodopa/carbidopa 100/25 (single-dose).

Detailed Description:

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

  Eligibility

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

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.
  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: NCT01533077

Locations
Canada, Quebec
Algorithme Pharma Inc.
Mount-Royal, Quebec, Canada, H3P 3P1
Sponsors and Collaborators
Bial - Portela C S.A.
Investigators
Principal Investigator: Eric Sicard, MD Algorithme Pharma Inc
  More Information

No publications provided

Responsible Party: Bial - Portela C S.A.
ClinicalTrials.gov Identifier: NCT01533077     History of Changes
Other Study ID Numbers: BIA-91067-117
Study First Received: January 24, 2012
Last Updated: June 20, 2012
Health Authority: Canada: Health Canada

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
Carbidopa
Levodopa
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014