Parkinson Disease
Conditions
Keywords
Parkinson Disease, BIA 9-1067
Brief summary
To investigate the effect of repeated dosing of BIA 9-1067 on the levodopa pharmacokinetics, in comparison to placebo and entacapone.
Detailed description
Single-centre, double-blind, randomised, parallel-group study in 80 young male and female healthy subjects.
Interventions
DRUGBIA 9-1067 5 mg
BIA 9-1067 OPC, Opicapone 5 mg
DRUGEntacapone
Entacapone 200 mg
DRUGPlacebo
placebo (four times a day)
standard release levodopa/carbidopa 100/25 mg (single-dose)
DRUGBIA 9-1067 15 mg
BIA 9-1067 OPC, Opicapone 15 mg
DRUGBIA 9-1067 30 mg
BIA 9-1067 OPC, Opicapone 30 mg
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Able and willing to give written informed consent. * Male or female subjects aged between 18 and 45 years, inclusive. * Subjects of body mass index (BMI) between 19 and 30 kg/m2, inclusive. * Healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG. * Negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab at screening. * Clinical laboratory test results clinically acceptable at screening and admission to the treatment period. * Negative screen for alcohol and drugs of abuse at screening and admission to the treatment period. * Non-smokers or ex-smokers for at least 3 months. * (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: intrauterine device (by the subject) and condoms (by the partner) or diaphragm (by the subject) and condoms (by the partner) or spermicide (by the subject) and condoms (by the partner). * (If female) She had a negative urine pregnancy test at screening and admission to the treatment period.
Exclusion criteria
* 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. * Clinically relevant surgical history. * Any abnormality in the coagulation tests. * Any abnormality in the liver function tests. * A history of relevant atopy or drug hypersensitivity. * A history or presence of narrow-angle glaucoma. * A suspicious undiagnosed skin lesions or a history of melanoma. * History of alcoholism or drug abuse. * Consumed more than 14 units of alcohol a week. * Significant infection or known inflammatory process at screening or admission to the treatment period. * Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to the treatment period. * Had used non-selective monoamine oxidase (MAO) inhibitors within 2 weeks of admission to the treatment period. * Had used medicines within 2 weeks of admission to the treatment period that may have affected the safety or other study assessments, in the investigator's opinion. * Had previously received BIA 9-1067. * Had used any investigational drug or participated in any clinical trial within 6 months prior to screening. * Had participated in more than 2 clinical trials within the 12 months prior to screening. * Had donated or received any blood or blood products within the 3 months prior to screening. * Vegetarians, vegans or had medical dietary restrictions. * Cannot communicate reliably with the investigator. * Unlikely to co-operate with the requirements of the study. * Unwilling or unable to gave written informed consent. * (If female) She was pregnant or breast-feeding. * (If female) She was of childbearing potential and she did not use an approved effective contraceptive method or she used oral contraceptives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Plasma Concentration of Levodopa | 8 days | Cmax - Maximum plasma concentration of levodopa following a single oral administration of Sinemet® 100/25 on Day 8, and 5 mg, 15 mg and 30 mg BIA 9-1067 once-daily (QD), 200 mg entacapone thrice-daily (TID), and placebo, for 8 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax - Time to Reach Maximum Plasma Concentration of Levodopa | 8 days | Tmax - Time to Reach maximum plasma concentration of levodopa following a single oral administration of Sinemet® 100/25 on Day 8, and 5 mg, 15 mg and 30 mg BIA 9-1067 once-daily (QD), 200 mg entacapone thrice-daily (TID), and placebo, for 8 days. |
| AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification. | 8 days | AUC0-t - Area under the plasma concentration-time curve (AUC) of levodopa from time zero to the last sampling time following a single oral administration of Sinemet® 100/25 on Day 8, and 5 mg, 15 mg and 30 mg BIA 9-1067 once-daily (QD), 200 mg entacapone thrice-daily (TID), and placebo, for 8 days |
| AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity | 8 days | AUC0-∞ - Area under the plasma concentration-time curve (AUC) of levodopa from time zero to infinity. |
Countries
Portugal
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Placebo at all the dosing times
Placebo: placebo (four times a day) | 16 |
| Group 2 Day 1 to 7:
BIA 9-1067 5 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose
Day 8:
BIA 9-1067 5 mg: 7 AM dose Placebo+ levodopa/carbidopa 100/25 mg: 8 AM dose
BIA 9-1067 5 mg: BIA 9-1067 OPC, Opicapone 5 mg
Placebo: placebo (four times a day)
levodopa/carbidopa: standard release levodopa/carbidopa 100/25 mg (single-dose) | 16 |
| Group 3 Day 1 to 7:
BIA 9-1067 15 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose
Day 8:
BIA 9-1067 15 mg: 7 AM dose Placebo+ levodopa/carbidopa 100/25 mg: 8 AM dose
Placebo: placebo (four times a day)
levodopa/carbidopa: standard release levodopa/carbidopa 100/25 mg (single-dose)
BIA 9-1067 15 mg: BIA 9-1067 OPC, Opicapone 15 mg | 18 |
| Group 4 Day 1 to 7:
BIA 9-1067 30 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose
Day 8:
BIA 9-1067 30 mg: 7 AM dose Placebo + levodopa/carbidopa 100/25 mg: 8 AM dose
Placebo: placebo (four times a day)
levodopa/carbidopa: standard release levodopa/carbidopa 100/25 mg (single-dose)
BIA 9-1067 30 mg: BIA 9-1067 OPC, Opicapone 30 mg | 16 |
| Group 5 Day 1 to 7:
Placebo: 7 AM dose; Entacapone 200 mg: 8 AM; 4 PM; 12 PM dose
Day 8:
Placebo: 7 AM dose Entacapone 200 mg + levodopa/carbidopa 100/25 mg: 8 AM dose
Entacapone: Entacapone 200 mg
Placebo: placebo (four times a day)
levodopa/carbidopa: standard release levodopa/carbidopa 100/25 mg (single-dose) | 16 |
| Total | 82 |
Baseline characteristics
| Characteristic | Group 1 | Group 2 | Group 3 | Group 4 | Group 5 | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 16 Participants | 18 Participants | 16 Participants | 16 Participants | 82 Participants |
| Sex: Female, Male Female | 8 Participants | 8 Participants | 9 Participants | 8 Participants | 8 Participants | 41 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 9 Participants | 8 Participants | 8 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 16 | 9 / 16 | 10 / 17 | 12 / 16 | 7 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 1 / 17 | 0 / 16 | 0 / 16 |
Outcome results
Primary
Cmax - Maximum Plasma Concentration of Levodopa
Cmax - Maximum plasma concentration of levodopa following a single oral administration of Sinemet® 100/25 on Day 8, and 5 mg, 15 mg and 30 mg BIA 9-1067 once-daily (QD), 200 mg entacapone thrice-daily (TID), and placebo, for 8 days
Time frame: 8 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 | Cmax - Maximum Plasma Concentration of Levodopa | 1076 ng/mL | Standard Deviation 292.7 |
| Group 2 | Cmax - Maximum Plasma Concentration of Levodopa | 1106 ng/mL | Standard Deviation 420.3 |
| Group 3 | Cmax - Maximum Plasma Concentration of Levodopa | 943 ng/mL | Standard Deviation 325.3 |
| Group 4 | Cmax - Maximum Plasma Concentration of Levodopa | 981 ng/mL | Standard Deviation 488.5 |
| Group 5 | Cmax - Maximum Plasma Concentration of Levodopa | 928 ng/mL | Standard Deviation 245 |
Secondary
AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity
AUC0-∞ - Area under the plasma concentration-time curve (AUC) of levodopa from time zero to infinity.
Time frame: 8 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 | AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity | 1649 ng.h/mL | Standard Deviation 313.3 |
| Group 2 | AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity | 1873 ng.h/mL | Standard Deviation 571.3 |
| Group 3 | AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity | 2233 ng.h/mL | Standard Deviation 578.3 |
| Group 4 | AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity | 2381 ng.h/mL | Standard Deviation 623.8 |
| Group 5 | AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity | 2253 ng.h/mL | Standard Deviation 540.7 |
Secondary
AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification.
AUC0-t - Area under the plasma concentration-time curve (AUC) of levodopa from time zero to the last sampling time following a single oral administration of Sinemet® 100/25 on Day 8, and 5 mg, 15 mg and 30 mg BIA 9-1067 once-daily (QD), 200 mg entacapone thrice-daily (TID), and placebo, for 8 days
Time frame: 8 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 | AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification. | 1578 ng.h/mL | Standard Deviation 320.3 |
| Group 2 | AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification. | 1785 ng.h/mL | Standard Deviation 574.8 |
| Group 3 | AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification. | 2102 ng.h/mL | Standard Deviation 569.6 |
| Group 4 | AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification. | 2202 ng.h/mL | Standard Deviation 605.6 |
| Group 5 | AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification. | 2146 ng.h/mL | Standard Deviation 538.6 |
Secondary
Tmax - Time to Reach Maximum Plasma Concentration of Levodopa
Tmax - Time to Reach maximum plasma concentration of levodopa following a single oral administration of Sinemet® 100/25 on Day 8, and 5 mg, 15 mg and 30 mg BIA 9-1067 once-daily (QD), 200 mg entacapone thrice-daily (TID), and placebo, for 8 days.
Time frame: 8 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 | Tmax - Time to Reach Maximum Plasma Concentration of Levodopa | 0.75 hours |
| Group 2 | Tmax - Time to Reach Maximum Plasma Concentration of Levodopa | 0.75 hours |
| Group 3 | Tmax - Time to Reach Maximum Plasma Concentration of Levodopa | 0.75 hours |
| Group 4 | Tmax - Time to Reach Maximum Plasma Concentration of Levodopa | 0.75 hours |
| Group 5 | Tmax - Time to Reach Maximum Plasma Concentration of Levodopa | 0.75 hours |