Parkinson's Disease (PD)
Conditions
Brief summary
The purpose of this study is to determine the effect of three single oral doses of nebicapone (50 mg, 100 mg and 200 mg) on the levodopa pharmacokinetics when administered in combination with a single-dose of controlled release levodopa 100 mg/benserazide 25 mg (Madopar® HBS 125).
Detailed description
STUDY DESIGN AND METHODOLOGY: Single centre, double-blind, randomised, placebo-controlled, 4-way crossover study with 4 single-dose treatment periods. The washout period between doses was 5 days or more. Screening: Subjects were screened for eligibility within 28 and 7 days before first admission. The screening consisted of: medical history; physical examination, vital signs; complete neurological examination; 12-lead ECG; haematology, coagulation, plasma biochemistry and urinalysis tests; HIV, hepatitis B and hepatitis C serology; drugs of abuse and alcohol screen; urine pregnancy test in women of childbearing potential; and review of the selection criteria. Treatment periods: In each treatment period, eligible subjects were admitted to the UFH on the day prior to receiving the study medication for: vital signs; medical history and physical examination updates; 12-lead ECG; haematology and plasma biochemistry; drugs of abuse and alcohol screen; and urine pregnancy test in women of childbearing potential. On first admission, subjects had a review of the selection criteria and were randomly assigned to one of the treatment sequences. On the morning of the dosing day, subjects received a dose of nebicapone/placebo concomitantly with a dose of Madopar® HBS 125 in fasting conditions (at least 8 hours) and remained in the UFH until at least 24 h post-dose; then, they left and returned for the next period or the follow-up visit. At given time-points between pre-dose and discharge, subjects were submitted to vital signs recording, brief neurological examination, 12-lead ECG, and blood sampling for plasma drug determination and erythrocyte S-COMT activity assay. At discharge, vital signs and ECG were recorded, and haematology and plasma biochemistry tests were performed. Blood samples (7 mL) for the determination of plasma concentration of levodopa, 3-O-methyldopa (3-OMD) and nebicapone, and for the assay of the erythrocyte S-COMT activity were taken at the following times: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose. Follow-up: A follow-up visit occurred approximately 7-10 days after discharge of last treatment period or early discontinuation for: medical history and physical examination updates; vital signs; 12-lead ECG; haematology, plasma biochemistry and urinalysis tests; and pregnancy test in women of childbearing potential.
Interventions
DRUGBIA 3-202
nebicapone 50 mg tablets; oral use
DRUGPlacebo
Nebicapone matching placebo tablets
DRUGlevodopa 100 mg / benserazide 25 mg
Madopar® HBS 125 (levodopa 100 mg / benserazide 25 mg) capsules; oral use
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Subjects were eligible for entry into the study if they fulfilled the following inclusion criteria: * Male or female subjects aged between 18 and 45 years, inclusive. * Subjects of body mass index (BMI) between 19 and 30 kg/m2, inclusive. * Subjects who were healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG. * Subjects who had clinical laboratory test results clinically acceptable at screening and admission to first treatment period. * Subjects who had negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab at screening. * Subjects who had a negative screen for alcohol and drugs of abuse at screening and admission to each treatment period. * Subjects who were non-smokers or who smoked ≤ 10 cigarettes or equivalent per day. * Subjects who were able and willing to give written informed consent. * (If female) 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. * (If female) She had a negative urine pregnancy test at screening and admission to each treatment period.
Exclusion criteria
Subjects were not eligible for entry into the study if they fulfilled the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed plasma drug concentration (Cmax) | pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose | Mean Cmax pharmacokinetic parameters of levodopa following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or nebicapone |
| Time of occurrence of Cmax (tmax) | pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose | Mean tmax pharmacokinetic parameters of levodopa following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or nebicapone |
| 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) | pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose | Mean AUC0-t pharmacokinetic parameters of levodopa following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or nebicapone |
| Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞) | pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose | Mean AUC0-00 pharmacokinetic parameters of levodopa following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or nebicapone |
| Apparent terminal half-life, calculated from ln 2/λz (t1/2) | pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose | Mean t1/2 pharmacokinetic parameters of levodopa following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or nebicapone |
Countries
Portugal
Outcome results
None listed