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Effect of Food on Opicapone

Phase 1
Completed
Conditions
Parkinson Disease
Interventions
Registration Number
NCT03116308
Lead Sponsor
Bial - Portela C S.A.
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).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
28
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
50 mg OPCOpicapone (OPC)Subjects received 50 mg OPC once-daily in the evening for 12 days. On D9 subjects were to receive 50 mg OPC in the evening after a minimum 6 hours fast. On D10 subjects were to receive the QD dose of 50 mg OPC thirty minutes after the start of moderate meal (with a previous 6 hours fast)
Primary Outcome Measures
NameTimeMethod
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

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

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

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

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

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

Secondary Outcome Measures
NameTimeMethod
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

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

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