Clinical trial NCT01533116: Effect of BIA 9-1067 at Steady-state on the Pharmacokinetics of Levodopa/Carbidopa and Levodopa/Benserazide
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson Disease
Keywords: Parkinson Disease
BIA 9-1067
Lead sponsor: Bial - Portela C S.A.
Sponsor class: INDUSTRY
First posted: 2012-02-15
Enrollment: 52
Sex: ALL
Minimum age (years): 25
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Eligibility 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.

Primary outcomes:
measure: Cmax - Maximum Plasma Concentration
timeFrame: pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h
measure: Tmax - Time to Maximum Plasma Concentration
timeFrame: pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h
measure: AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point
timeFrame: pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h
measure: tEmax - Time of Occurrence of Maximum Observed Effect on S-COMT Activity
timeFrame: pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h
measure: AUEC0-24 - Area Under the Effect-time Curve (AUEC) to 24 h Post-dose
timeFrame: pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h
Secondary outcomes:
Other outcomes:
Locations:
city: Mount-Royal
country: Canada
facility: Algorithme Pharma Inc.
state: Quebec
Study officials:
affiliation: Algorithme Pharma Inc
name: Eric Sicard, MD
role: PRINCIPAL_INVESTIGATOR
References: