Parkinson's Disease (PD)
Conditions
Keywords
Parkinson's disease (PD), Opicapone, BIA 9-1067
Brief summary
To investigate the effect of three single oral doses of BIA 9-1067 (25 mg, 50 mg and 100 mg) on the levodopa pharmacokinetics when administered in combination with a single-dose of controlled-release levodopa 100 mg/benserazide 25 mg (Madopar HBS).
Detailed description
Single centre, double-blind, randomized, placebo-controlled, crossover study with four consecutive single-dose treatment periods. The washout period between doses was to be at least10 days. On each treatment period (25, 50 and 100 mg BIA 9-1067 or placebo), after completion of pre-dose assessments, BIA 9-1067-Placebo was to be administered concomitantly with the dose of Madopar HBS; post-dose assessments were to be completed and subjects were to be discharged 72 h post-dose.
Interventions
DRUGPlacebo
PLC, Placebo
DRUGMadopar® HBS
controlled-release levodopa 100 mg/benserazide 25 mg
DRUGBIA 9-1067
OPC, Opicapone
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Male subjects 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 that were clinically acceptable at screening and admission to first treatment period. * Subjects 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. * Subjects who had/were negative for 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.
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, endocrine, 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 glaucoma. * Subjects who had a history of alcoholism or drug abuse. * Subjects who consumed more than 21 units of alcohol a week. * Subjects who had a significant infection or known inflammatory process on screening or first admission. * Subjects who had acute gastrointestinal symptoms at the time of screening or first admission (e.g., nausea, vomiting, diarrhoea, heartburn). * Subjects who used medicines within 2 weeks of first admission that, in the opinion of the investigator, may affect the safety or other study assessments. * Subjects who used any investigational drug or participated in any clinical trial within 2 months of their first admission. * Subjects who donated or received any blood or blood products within the previous 2 months prior to screening. * Subjects who were vegetarians, vegans or have 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. * Subjects who were unwilling or unable to give written informed consent. * Subjects who were BIAL - Portela & Cª, SA employees.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-t - Area Under the Plasma Concentration-time Curve | pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose. | Primary pharmacokinetic parameter: Area under the plasma concentration-time curve for levodopa |
| Cmax - Maximum Observed Plasma Concentration of Levodopa | pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose. | Primary pharmacokinetic parameter: Levodopa maximum observed plasma concentration (Cmax) (ng/mL) |
| AUC0-∞ - AUC From Time Zero to Infinity | pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose. | Primary pharmacokinetic parameter: Area under the plasma concentration-time curve from time zero to infinity for levodopa |
| Tmax - Time to Cmax | pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose. | Primary pharmacokinetic parameter: tmax - time to Cmax |
Countries
Portugal
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BIA 9-1067: 25, 50, 100, Placebo Period 1: BIA 9-1067 25 mg Period 2: BIA 9-1067 50 mg Period 3: BIA 9-1067 100 mg Period 4: Placebo
BIA 9-1067/Placebo was to be administered concomitantly with the dose of Madopar® HBS (Single-dose of controlled-release levodopa/benserazide 100/25 mg: 1 capsule of Madopar® HBS.)
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Madopar® HBS: controlled-release levodopa 100 mg/benserazide 25 mg | 6 |
| BIA 9-1067: 50, 100, Placebo, 25 Period 1: BIA 9-1067 50 mg Period 2: BIA 9-1067 100 mg Period 3: Placebo Period 4: BIA 9-1067 25 mg
BIA 9-1067/Placebo was to be administered concomitantly with the dose of Madopar® HBS (Single-dose of controlled-release levodopa/benserazide 100/25 mg: 1 capsule of Madopar® HBS.)
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Madopar® HBS: controlled-release levodopa 100 mg/benserazide 25 mg | 6 |
| BIA 9-1067: 100, Placebo, 25, 50 Period 1: BIA 9-1067 100 mg Period 2: Placebo Period 3: BIA 9-1067 25 mg Period 4: BIA 9-1067 50 mg
BIA 9-1067/Placebo was to be administered concomitantly with the dose of Madopar® HBS (Single-dose of controlled-release levodopa/benserazide 100/25 mg: 1 capsule of Madopar® HBS.)
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Madopar® HBS: controlled-release levodopa 100 mg/benserazide 25 mg | 5 |
| BIA 9-1067: Placebo, 25, 50, 100 Period 1: Placebo Period 2: BIA 9-1067 25 mg Period 3: BIA 9-1067 50 mg Period 4: BIA 9-1067 100 mg
BIA 9-1067/Placebo was to be administered concomitantly with the dose of Madopar® HBS (Single-dose of controlled-release levodopa/benserazide 100/25 mg: 1 capsule of Madopar® HBS.)
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Madopar® HBS: controlled-release levodopa 100 mg/benserazide 25 mg | 5 |
| Total | 22 |
Baseline characteristics
| Characteristic | BIA 9-1067: 25, 50, 100, Placebo | BIA 9-1067: 50, 100, Placebo, 25 | BIA 9-1067: 100, Placebo, 25, 50 | BIA 9-1067: Placebo, 25, 50, 100 | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 5 Participants | 5 Participants | 22 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 5 Participants | 5 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 21 | 4 / 22 | 3 / 22 | 2 / 21 |
| serious Total, serious adverse events | 0 / 21 | 0 / 22 | 0 / 22 | 0 / 21 |
Outcome results
Primary
AUC0-∞ - AUC From Time Zero to Infinity
Primary pharmacokinetic parameter: Area under the plasma concentration-time curve from time zero to infinity for levodopa
Time frame: pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose.
Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid data for all treatment periods.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIA 9-1067 25 mg | AUC0-∞ - AUC From Time Zero to Infinity | 1190 ng.h/mL | Standard Deviation 441 |
| BIA 9-1067 50 mg | AUC0-∞ - AUC From Time Zero to Infinity | 1181 ng.h/mL | Standard Deviation 373 |
| BIA 9-1067 100 mg | AUC0-∞ - AUC From Time Zero to Infinity | 1326 ng.h/mL | Standard Deviation 604 |
| Placebo | AUC0-∞ - AUC From Time Zero to Infinity | 1086 ng.h/mL | Standard Deviation 380 |
Primary
AUC0-t - Area Under the Plasma Concentration-time Curve
Primary pharmacokinetic parameter: Area under the plasma concentration-time curve for levodopa
Time frame: pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose.
Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid data for all treatment periods.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIA 9-1067 25 mg | AUC0-t - Area Under the Plasma Concentration-time Curve | 1084 ng.h/mL | Standard Deviation 398 |
| BIA 9-1067 50 mg | AUC0-t - Area Under the Plasma Concentration-time Curve | 1064 ng.h/mL | Standard Deviation 365 |
| BIA 9-1067 100 mg | AUC0-t - Area Under the Plasma Concentration-time Curve | 1140 ng.h/mL | Standard Deviation 592 |
| Placebo | AUC0-t - Area Under the Plasma Concentration-time Curve | 933 ng.h/mL | Standard Deviation 422 |
Primary
Cmax - Maximum Observed Plasma Concentration of Levodopa
Primary pharmacokinetic parameter: Levodopa maximum observed plasma concentration (Cmax) (ng/mL)
Time frame: pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose.
Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid data for all treatment periods.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIA 9-1067 25 mg | Cmax - Maximum Observed Plasma Concentration of Levodopa | 314 ng/mL | Standard Deviation 110 |
| BIA 9-1067 50 mg | Cmax - Maximum Observed Plasma Concentration of Levodopa | 266 ng/mL | Standard Deviation 77.5 |
| BIA 9-1067 100 mg | Cmax - Maximum Observed Plasma Concentration of Levodopa | 263 ng/mL | Standard Deviation 94.9 |
| Placebo | Cmax - Maximum Observed Plasma Concentration of Levodopa | 260 ng/mL | Standard Deviation 119 |
Primary
Tmax - Time to Cmax
Primary pharmacokinetic parameter: tmax - time to Cmax
Time frame: pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose.
Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid data for all treatment periods.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| BIA 9-1067 25 mg | Tmax - Time to Cmax | 2.50 hours |
| BIA 9-1067 50 mg | Tmax - Time to Cmax | 2.50 hours |
| BIA 9-1067 100 mg | Tmax - Time to Cmax | 2.00 hours |
| Placebo | Tmax - Time to Cmax | 2.00 hours |