Parkinson's Disease
Conditions
Brief summary
Single-centre, open-label, randomised, two-way cross-over study consisting of 2 periods separated by a washout period of 14 days or more.
Detailed description
Single-centre, open-label, randomised, two-way cross-over study consisting of 2 periods separated by a washout period of 14 days or more. In one period, subjects received three single-doses of 1 g paracetamol separated by 6 hours and 1.5 hours after the last paracetamol dose a single-dose of 50 mg OPC was administered.In the other period, a single-dose of 50 mg OPC was administered alone.
Interventions
DRUGBIA 9-1067
BIA 9-1067 50 mg
DRUGParacetamol
Paracetamol 1g
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects who are 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 19.0 and 30.0 kg/m2, inclusive. * Subjects who are healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG. * Subjects who have negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab at screening. * Subjects who have clinical laboratory test results clinically acceptable at screening and admission to each treatment period. * Subjects who have a negative screen for alcohol and drugs of abuse at screening and admission to each treatment period. * Subjects who are non-smokers or ex-smokers for at least 3 months. * (If female) She is not of childbearing potential by reason of surgery or, if of childbearing potential, she uses an effective non-hormonal method of contraception (intrauterine device or intrauterine system; condom or occlusive cap \[diaphragm or cervical or vault caps\] with spermicidal foam or gel or film or cream or suppository; true abstinence; or vasectomized male partner, provided that he is the sole partner of that subject) for all the duration of the study. * (If female) She has a negative serum pregnancy test at screening and a negative urine pregnancy test on Day -1 of each treatment period.
Exclusion criteria
* Subjects who have 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 have a clinically relevant surgical history. * Subjects who have any clinically relevant abnormality in the coagulation tests. * Subjects who have any clinically relevant abnormality in the liver function tests (a case-by-case decision for any abnormality must be discussed with the Sponsor before inclusion). * Subjects who have a history of relevant atopy or drug hypersensitivity, particularly to paracetamol or any COMT inhibitor. * Subjects who have a history of alcoholism or drug abuse. * Subjects who consume more than 14 units of alcohol a week. * Subjects who have a significant infection or known inflammatory process at screening or admission to each treatment period. * Subjects who have acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to each treatment period. * Subjects who have received paracetamol within 2 weeks of admission to the first period. * Subjects who have used any other medicines within 2 weeks of admission to first period that may affect the safety or other study assessments, in the investigator's opinion. * Subjects who have previously received OPC. * Subjects who have used any investigational drug or participated in any clinical trial within 90 days prior to screening. * Subjects who have participated in more than 2 clinical trials within the 12 months prior to screening. * Subjects who have donated or received any blood or blood products within the 3 months prior to screening. * Subjects who are vegetarians, vegans or have medical dietary restrictions. * Subjects who cannot communicate reliably with the investigator. * Subjects who are unlikely to co-operate with the requirements of the study. * Subjects who are unwilling or unable to give written informed consent. * (If female) She is pregnant or breast-feeding. * (If female) She is of childbearing potential and she does not use an approved effective contraceptive method or she uses oral contraceptives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Plasma Concentration | before and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hour post-OPC dose | Cmax - Maximum plasma concentration of opicapone on Day 12 following an oral single-dose of 50 mg OPC administered alone or 1.5 h after last 1 g Paracetamol administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax - Time of Occurrence of Cmax | before and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hour post-OPC dose | Tmax - time of occurrence of Cmax following an oral single-dose of 50 mg OPC administered alone or 1.5 h after last 1 g Paracetamol administration. |
| AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification | before and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hour post-OPC dose | AUC0-t - area under the plasma concentration-time curve (AUC) from time zero to the last sampling time following an oral single-dose of 50 mg OPC administered alone or 1.5 h after last 1 g Paracetamol administration |
| AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity. | before and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hour post-OPC dose | AUC0-∞ - AUC from time 0 to infinity following an oral single-dose of 50 mg OPC administered alone or 1.5 h after last 1 g Paracetamol administration. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Period 1 OPC + Paracetamol; Period 2 OPC Period 1 BIA 9-1067 (Opicapone, OPC) + Paracetamol; Period 2 BIA 9-1067 (Opicapone, OPC)
BIA 9-1067: BIA 9-1067 50 mg
Paracetamol: Paracetamol 1g | 14 |
| Period 1 OPC; Period 2 OPC+ Paracetamol Period 1 BIA 9-1067 (Opicapone, OPC) Period 2 BIA 9-1067 (Opicapone, OPC) + Paracetamol;
BIA 9-1067: BIA 9-1067 50 mg
Paracetamol: Paracetamol 1g | 14 |
| Total | 28 |
Baseline characteristics
| Characteristic | Period 1 OPC + Paracetamol; Period 2 OPC | Period 1 OPC; Period 2 OPC+ Paracetamol | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 14 Participants | 28 Participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 28 | 1 / 28 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 |
Outcome results
Primary
Cmax - Maximum Plasma Concentration
Cmax - Maximum plasma concentration of opicapone on Day 12 following an oral single-dose of 50 mg OPC administered alone or 1.5 h after last 1 g Paracetamol administration
Time frame: before and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hour post-OPC dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Opicapone Alone | Cmax - Maximum Plasma Concentration | 895 ng/mL | Standard Deviation 375.9 |
| Opicapone Plus Paracetamol | Cmax - Maximum Plasma Concentration | 986 ng/mL | Standard Deviation 355 |
Secondary
AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity.
AUC0-∞ - AUC from time 0 to infinity following an oral single-dose of 50 mg OPC administered alone or 1.5 h after last 1 g Paracetamol administration.
Time frame: before and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hour post-OPC dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Opicapone Alone | AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity. | 2451 ng.h/mL | Standard Deviation 882 |
| Opicapone Plus Paracetamol | AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity. | 2850 ng.h/mL | Standard Deviation 1188 |
Secondary
AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) 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) from time zero to the last sampling time following an oral single-dose of 50 mg OPC administered alone or 1.5 h after last 1 g Paracetamol administration
Time frame: before and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hour post-OPC dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Opicapone Alone | AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification | 2416 ng.h/mL | Standard Deviation 884.3 |
| Opicapone Plus Paracetamol | AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification | 2818 ng.h/mL | Standard Deviation 1194 |
Secondary
Tmax - Time of Occurrence of Cmax
Tmax - time of occurrence of Cmax following an oral single-dose of 50 mg OPC administered alone or 1.5 h after last 1 g Paracetamol administration.
Time frame: before and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hour post-OPC dose
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Opicapone Alone | Tmax - Time of Occurrence of Cmax | 2.0 hours |
| Opicapone Plus Paracetamol | Tmax - Time of Occurrence of Cmax | 2.0 hours |