Parkinson Disease
Conditions
Brief summary
The purpose of this study is to investigate the effect of food on the catechol-O-Methyltransferase (COMT) activity after repeated doses of opicapone (OPC, development code BIA 9-1067) in healthy subjects and to characterize the effects of food on the pharmacokinetics (PK) and tolerability of OPC after repeated doses.
Detailed description
Single-centre, open-label, single-arm study in 28 healthy subjects. Subjects received a single-dose of 50 mg OPC once-daily (QD) in the evening for 12 days. On Day 1 (D1), 50 mg OPC was orally administered in the evening (reference hour for all other administrations) after a minimum of 6 hours fast. From D2 to D8 subjects were in ambulatory and received 50 mg OPC once-daily (evening administration after 2 hours fast). On D9, 50 mg OPC was orally administered in the evening after a minimum of 6 hours fast. On D10, 50 mg OPC was orally administered in the evening, thirty minutes after the start of a moderate meal (with a previous 6 hours fast). On D11 and D12 subjects received the last doses of 50 mg OPC (evening administration after 2 hours fast).
Interventions
DRUGOpicapone (OPC)
50 mg OPC capsules; oral route
Sponsors
Bial - Portela C S.A.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Able and willing to give written informed consent and to comply with the study restrictions. * Male or female subjects aged between 18 and 45 years, inclusive. * 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-HCV Ab and HIV-1 and HIV-2 Ab at screening. * Clinical laboratory test results clinically acceptable at screening and admission. * Negative screen for alcohol and drugs of abuse at screening and admission. * Non-smokers or ex-smokers for at least 3 months. * If female: * 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. * Negative serum pregnancy test at screening and a negative urine pregnancy test on admission.
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. * Clinically relevant abnormality in the coagulation tests. * Clinically relevant abnormality in the liver function tests. * History of relevant atopy or drug hypersensitivity, particularly to any COMT inhibitor. * History of alcoholism or drug abuse. * Consume more than 14 units of alcohol a week. * Significant infection or known inflammatory process at screening or admission. * Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission. * Used medicines within 2 weeks of admission that may affect the safety or other study assessments, in the investigator's opinion. * Previously received OPC. * Used any investigational drug or participated in any clinical trial within 90 days prior to screening. * Participated in more than 2 clinical trials within the 12 months prior to screening. * Donated or received any blood or blood products within the 3 months prior to screening. * Vegetarians, vegans or have medical dietary restrictions. * Cannot communicate reliably with the investigator. * Unlikely to co-operate with the requirements of the study. * If female: * Pregnant or breast-feeding. * Of childbearing potential and not used an approved effective contraceptive method or she uses oral contraceptives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed effect on COMT activity (Emax) - Day 10 (fed state) | Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose | Pharmacodynamic parameters for opicapone |
| Area under the effect-time curve (AUEC) - Day 10 (fed state) | Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose | Pharmacodynamic parameters for opicapone |
| Maximum observed effect on COMT activity (Emax) - Day 9 (fasted state) | Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose | Pharmacodynamic parameters for opicapone |
| Time to occurrence of Emax (tEmax) - Day 9 (fasted state) | Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose | Pharmacodynamic parameters for opicapone |
| Area under the effect-time curve (AUEC) - Day 9 (fasted state) | Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose | Pharmacodynamic parameters for opicapone |
| Time to occurrence of Emax (tEmax) - Day 10 (fed state) | Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose | Pharmacodynamic parameters for opicapone |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time of occurrence of Cmax (tmax) - Day 9 (fasted state) | Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose | Pharmacokinetic parameters for opicapone |
| Maximum observed plasma concentration (Cmax) - Day 10 (fed state) | Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose | Pharmacokinetic parameters for opicapone |
| Time of occurrence of Cmax (tmax) - Day 10 (fed state) | Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose | Pharmacokinetic parameters for opicapone |
| Maximum observed plasma concentration (Cmax) - Day 9 (fasted state) | Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose | Pharmacokinetic parameters for opicapone |
Outcome results
None listed