Effect of BIA 9-1067 at Steady-state on the Pharmacokinetics of Levodopa/Carbidopa and Levodopa/Benserazide

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bial - Portela C S.A.
ClinicalTrials.gov Identifier:
NCT01533116
First received: January 24, 2012
Last updated: June 20, 2012
Last verified: June 2012
  Purpose

To investigate the effect of BIA 9-1067 in steady-state conditions on the levodopa pharmacokinetics


Condition Intervention Phase
Parkinson Disease
Drug: BIA 9-1067
Drug: Placebo
Drug: levodopa/carbidopa
Drug: levodopa/benserazide
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Effect of BIA 9-1067 at Steady-state on the Pharmacokinetics of a Single-dose of Immediate-release 100/25 mg Levodopa/Carbidopa and 100/25 mg Levodopa/Benserazide in Healthy Subjects

Resource links provided by NLM:


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

Primary Outcome Measures:
  • time of occurrence of Cmax (tmax) [ Time Frame: pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h ] [ Designated as safety issue: No ]
    Pharmacokinetic and pharmacodynamic assessments


Secondary Outcome Measures:
  • 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 (AUC 0-t) [ Time Frame: pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters

  • AUC from time zero to 24 h post-dose (AUC0-24) [ Time Frame: pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters

  • AUC from time zero to infinity (AUC0-∞) [ Time Frame: pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters

  • Maximum observed effect on COMT activity, Emax [ Time Frame: pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h ] [ Designated as safety issue: No ]
    Pharmacodynamic parameters

  • Time to occurrence of Emax, tEmax [ Time Frame: pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h ] [ Designated as safety issue: No ]
    Pharmacodynamic parameters

  • Area under the effect-time curve, AUEC [ Time Frame: pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h ] [ Designated as safety issue: No ]
    Pharmacodynamic parameters

  • Maximum percent inhibition of COMT activity, calculated as [(E0-Emax)/E0]*100, where E0 is the baseline (pre-dose of Day 1) value [ Time Frame: pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h ] [ Designated as safety issue: No ]
    Pharmacodynamic parameters

  • Number of Participants with Adverse Events [ Time Frame: monitored throughout the study ] [ Designated as safety issue: No ]
    Safety analysis: 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: 48
Study Start Date: March 2009
Study Completion Date: March 2010
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIA 9-1067 Drug: BIA 9-1067
5 mg, 15 mg and 30 mg of BIA 9-1067 (once-daily)
Placebo Comparator: Placebo Drug: Placebo
Placebo (once-daily)
Active Comparator: levodopa/carbidopa Drug: levodopa/carbidopa
levodopa/carbidopa 100/25 mg (single-dose)
Active Comparator: levodopa/benserazide Drug: levodopa/benserazide
levodopa/benserazide 100/25 mg (single-dose).

Detailed Description:

Single centre, randomized, double-blind, gender-balanced, placebo-controlled study in 4 groups of healthy subjects

  Eligibility

Ages Eligible for Study:   25 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 25 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 and admission to the treatment period.
  • 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.
  • 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01533116

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: NCT01533116     History of Changes
Other Study ID Numbers: BIA-91067-118
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
Benserazide
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 April 21, 2014