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 immediate-release levodopa/carbidopa 100/25 mg (Sinemet® 100/25)
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 least 14 days. On each treatment period, after completion of pre-dose assessments, BIA 9-1067/Placebo was to be administered concomitantly with the dose of Sinemet® 100/25; post-dose assessments were to be completed and subjects were to be discharged 72 h post-dose. Subjects were to attend four treatment periods and were to receive a different dose of BIA 9-1067 (25 mg, 50 mg and 100 mg) or placebo during each of these treatment periods.
Interventions
DRUGBIA 9-1067
OPC, Opicapone
DRUGPlacebo
PLC, Placebo
DRUGSinemet® 100/25
Immediate-release levodopa/carbidopa 100/25 mg
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
1. 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. 2. Male volunteers. 3. Volunteers of at least 18 years of age but not older than 45 years. 4. Volunteers with body mass index (BMI) greater than or equal to 19 and below 30 kg/m2. 5. Volunteers who are non- or ex-smokers. An ex-smoker is defined as someone who completely stopped smoking for at least 12 months before day 1 of this study. 6. Volunteers who are healthy as determined by pre-study (at screening) medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG. 7. Volunteers who have clinical laboratory test results judged clinically acceptable (within the laboratory's stated normal range; if not within this range, they must be without any clinical significance) at screening and admission to first treatment period. 8. Volunteers who have 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. 9. Volunteers who have negative screen of ethyl alcohol and drugs of abuse at screening. 10. Due to unknown risks and potential harm to the unborn fetus, sexually active men must agree to use a medically acceptable form of contraception throughout the study.
Exclusion criteria
1. Volunteers who do not conform to the above inclusion criteria, or in case of 2. Volunteers who have a clinically relevant surgical history. 3. Volunteers who have a clinically relevant family history. 4. Volunteers who have a history of relevant atopy. 5. Volunteers who have a significant infection or known inflammatory process at screening or first admission. 6. Volunteers who have acute gastrointestinal symptoms at the time of screening or first admission (e.g., nausea, vomiting, diarrhoea, heartburn). 7. Volunteers who are vegetarians, vegans or have medical dietary restrictions. 8. Volunteers who cannot communicate reliably with the investigator. 9. Volunteers who are unlikely to co-operate with the requirements of the study. 10. Significant history of hypersensitivity to BIA 9-1067, tolcapone, entacapone, levodopa, carbidopa or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs. 11. 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. 12. History of significant gastrointestinal, liver or kidney disease that may affect drug bioavailability. 13. Presence or history of significant cardiovascular, pulmonary, hematologic, neurologic, psychiatric, lymphatic, musculoskeletal, genitourinary, endocrine, immunologic, dermatologic or connective tissue disease. 14. Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases. 15. Presence of significant heart disease or disorder according to ECG. 16. Presence of suspicious undiagnosed skin lesions or a history of melanoma. 17. Previous history of Neuroleptic Malignant Syndrome (NMS) and/or nontraumatic rhabdomyolysis. 18. Presence or history of significant glaucoma. 19. Use of prescription medications including MAO inhibitors within 28 days before day 1 of the study. 20. Use of over-the-counter (OTC) products within 7 days before day 1 of the study. 21. 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). 22. Any clinically significant illness in the previous 28 days before day 1 of this study. 23. Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin and rifampin), in the previous 28 days before day 1 of this study. 24. 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. 25. 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. 26. 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. 27. Positive urine screening of ethyl alcohol or drugs of abuse at admission to any treatment period. 28. Any history of tuberculosis and/or prophylaxis for tuberculosis. 29. Positive results to HIV, HBsAg or anti-HCV tests. 30. Participation in any previous clinical study with BIA 9-1067 within 84 days before day 1 of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Plasma Concentration of Levodopa | pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose | Levodopa maximum observed plasma concentration (Cmax) (ng/mL) |
| Tmax - Time of Occurrence of Cmax of Levodopa | pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose | Tmax - time of occurrence of Cmax of levodopa. |
| AUC0-t - Area Under the Plasma Concentration-time Curve | pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose | Area under the plasma concentration-time curve for levodopa |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 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- 067/Placebo was to be administered concomitantly with the a single-dose of immediate-release levodopa/carbidopa 100/25 mg: 1 tablet of Sinemet® 100/25
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Sinemet® 100/25: Immediate-release levodopa/carbidopa 100/25 mg | 4 |
| Group 2 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- 067/Placebo was to be administered concomitantly with the a single-dose of immediate-release levodopa/carbidopa 100/25 mg: 1 tablet of Sinemet® 100/25
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Sinemet® 100/25: Immediate-release levodopa/carbidopa 100/25 mg | 4 |
| Group 3 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- 067/Placebo was to be administered concomitantly with the a single-dose of immediate-release levodopa/carbidopa 100/25 mg: 1 tablet of Sinemet® 100/25
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Sinemet® 100/25: Immediate-release levodopa/carbidopa 100/25 mg | 4 |
| Group 4 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- 067/Placebo was to be administered concomitantly with the a single-dose of immediate-release levodopa/carbidopa 100/25 mg: 1 tablet of Sinemet® 100/25
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Sinemet® 100/25: Immediate-release levodopa/carbidopa 100/25 mg | 4 |
| Total | 16 |
Baseline characteristics
| Characteristic | Group 1 | Group 2 | Group 3 | Group 4 | 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 | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 16 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 16 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 | 7 / 15 | 9 / 16 | 5 / 15 | 4 / 14 |
| serious Total, serious adverse events | 0 / 15 | 0 / 16 | 0 / 15 | 0 / 14 |
Outcome results
Primary
AUC0-t - Area Under the Plasma Concentration-time Curve
Area under the plasma concentration-time curve for levodopa
Time frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIA 9-1067 25 mg | AUC0-t - Area Under the Plasma Concentration-time Curve | 1629 ng.h/mL | Standard Deviation 394.2 |
| BIA 9-1067 50 mg | AUC0-t - Area Under the Plasma Concentration-time Curve | 1727 ng.h/mL | Standard Deviation 405.8 |
| BIA 9-1067 100 mg | AUC0-t - Area Under the Plasma Concentration-time Curve | 1853 ng.h/mL | Standard Deviation 361.3 |
| Placebo | AUC0-t - Area Under the Plasma Concentration-time Curve | 1629 ng.h/mL | Standard Deviation 438.2 |
Primary
Cmax - Maximum Observed Plasma Concentration of Levodopa
Levodopa maximum observed plasma concentration (Cmax) (ng/mL)
Time frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIA 9-1067 25 mg | Cmax - Maximum Observed Plasma Concentration of Levodopa | 896 ng/mL | Standard Deviation 300.2 |
| BIA 9-1067 50 mg | Cmax - Maximum Observed Plasma Concentration of Levodopa | 1088 ng/mL | Standard Deviation 315.5 |
| BIA 9-1067 100 mg | Cmax - Maximum Observed Plasma Concentration of Levodopa | 1014 ng/mL | Standard Deviation 267.7 |
| Placebo | Cmax - Maximum Observed Plasma Concentration of Levodopa | 889 ng/mL | Standard Deviation 307.6 |
Primary
Tmax - Time of Occurrence of Cmax of Levodopa
Tmax - time of occurrence of Cmax of levodopa.
Time frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BIA 9-1067 25 mg | Tmax - Time of Occurrence of Cmax of Levodopa | 0.5 hours |
| BIA 9-1067 50 mg | Tmax - Time of Occurrence of Cmax of Levodopa | 0.5 hours |
| BIA 9-1067 100 mg | Tmax - Time of Occurrence of Cmax of Levodopa | 0.5 hours |
| Placebo | Tmax - Time of Occurrence of Cmax of Levodopa | 0.5 hours |