Clinical trial NCT02763852: Pharmacokinetic-Pharmacodynamic Interaction Between Four Different Single Doses of BIA 3-202 and a Single Dose of Levodopa/Benserazide (100/25 mg)
Official title: Pharmacokinetic-Pharmacodynamic Interaction Between Four Different Single Doses of BIA 3-202 and a Single Dose of Levodopa/Benserazide (100/25 mg): a Double-blind, Randomised, Crossover, Placebo Controlled Study in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson's Disease
Keywords: Parkinson's Disease
Nebicapone
Lead sponsor: Bial - Portela C S.A.
Sponsor class: INDUSTRY
First posted: 2016-05-05
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the tolerability, pharmacokinetic profile of BIA 3-202 and its metabolites, and the pharmacokinetic and pharmacodynamic interaction between 4 different single doses of BIA 3-202 (50 mg, 100 mg, 200 mg and 400 mg) and a single dose of standard levodopa 100 mg/benserazide 25 mg (Madopar® 125) in adult male and female healthy volunteers.

Detailed description: This was a single centre, double-blind, randomised, placebo-controlled, single-graded-dose, crossover study with five single-dose treatment periods. The washout period between doses was 15±2 days. For each of the five treatment periods, volunteers were to be admitted at the UFH on the day before the treatment day. On each treatment period, the pre-dose assessment were to be completed, BIA 3-202/Placebo was to be administered concomitantly with the dose of Madopar® 125 and post-dose assessments were to be completed. Subjects were discharged 30 h post-dose. Subjects should attend five treatment periods and were to receive a different dose of BIA 3-202 or placebo during each of these treatment periods.

Eligibility criteria: Inclusion Criteria:

* Male and female subjects aged between 18 and 45 years, inclusive.
* Subjects of body mass index (BMI) between 19 and 28 kg/m2, inclusive.
* Subjects who were healthy as determined by pre study medical history, physical examination, and 12- lead ECG.
* Subjects who had clinical laboratory tests acceptable to the investigator.
* Subjects who were negative for HBsAg, anti-HCV Ab and HIV-1 and HIV-2 Ab tests at screening.
* Subjects who were negative for drugs of abuse at screening and admission.
* Subjects who were non-smokers or who smoked less than 10 cigarettes or equivalent per day.
* Subjects who were able and willing to give written informed consent.
* (If a woman) 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, intrauterine device or abstinence.

Exclusion Criteria:

Subjects who did not conform to the above inclusion criteria, OR

* Subjects who had a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders.
* Subjects who had a clinically relevant surgical history.
* Subjects who had a clinically relevant family history.
* Subjects who had a history of relevant atopy.
* Subjects who had a history of relevant drug hypersensitivity.
* Subjects who had a history of alcoholism or drug abuse.
* Subjects who consumed more than 28 units of alcohol a week.
* Subjects who had a significant infection or known inflammatory process on screening and/or admission.
* Subjects who had acute gastrointestinal symptoms at the time of screening and/or admission (e.g., nausea, vomiting, diarrhoea, heartburn).
* Subjects who had an acute infection such as influenza at the time of screening and/or admission.
* Subjects who had used prescription drugs within 4 weeks of first dosing.
* Subjects who had used oral contraceptives or over the counter medication excluding oral routine vitamins but including mega dose vitamin therapy within one week of first dosing.
* Subjects who had used any investigational drug and/or participated in any clinical trial within 3 months of their first admission to the study.
* Subjects who had previously received BIA 3-202.
* Subjects who had donated and/or received any blood or blood products within the previous 3 months prior to screening.
* Subjects who were vegetarians, vegans and/or had medical dietary restrictions.
* Subjects who could not communicate reliably with the investigator.
* Subjects who were unlikely to co-operate with the requirements of the study.
* (If woman) She was pregnant or breast-feeding.
* (If woman) She was at childbearing potential and she did not use an approved effective contraceptive method or she used oral contraceptives.
* Subjects who were unwilling or unable to give written informed consent.

Primary outcomes:
measure: Maximum observed plasma concentration (Cmax)
timeFrame: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 18 and 24 h post-dose
measure: Area under the plasma concentration time curve extrapolated to infinity (AUC0-∞)
timeFrame: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 18 and 24 h post-dose
measure: Apparent terminal elimination half-life (t1/2)
timeFrame: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 18 and 24 h post-dose
Secondary outcomes:
Other outcomes:
Locations:
city: S. Mamede do Coronado
country: Portugal
facility: Human Pharmacology Unit - BIAL - Portela & Ca, S.A.
Study officials:
References: