Effect of Food on Opicapone

Effect of Food on Opicapone Bioavailability and Pharmacodynamics in Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Opicapone (OPC)

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).

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 50 mg 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)	Drug: Opicapone (OPC); 50 mg OPC capsules; oral route; Other Names: Ongentys; BIA 9-1067

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed effect on COMT activity (Emax) - Day 9 (fasted state)	Pharmacodynamic parameters for opicapone	Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose
Time to occurrence of Emax (tEmax) - Day 9 (fasted state)	Pharmacodynamic parameters for opicapone	Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose
Area under the effect-time curve (AUEC) - Day 9 (fasted state)	Pharmacodynamic parameters for opicapone	Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose
Maximum observed effect on COMT activity (Emax) - Day 10 (fed state)	Pharmacodynamic parameters for opicapone	Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose
Time to occurrence of Emax (tEmax) - Day 10 (fed state)	Pharmacodynamic parameters for opicapone	Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose
Area under the effect-time curve (AUEC) - Day 10 (fed state)	Pharmacodynamic parameters for opicapone	Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed plasma concentration (Cmax) - Day 9 (fasted state)	Pharmacokinetic parameters for opicapone	Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose
Time of occurrence of Cmax (tmax) - Day 9 (fasted state)	Pharmacokinetic parameters for opicapone	Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose
Maximum observed plasma concentration (Cmax) - Day 10 (fed state)	Pharmacokinetic parameters for opicapone	Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose
Time of occurrence of Cmax (tmax) - Day 10 (fed state)	Pharmacokinetic parameters for opicapone	Before and ½, 1, 2, 3, 4, 6, 12 and 24 h post-dose

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2014
• Primary Completion (Actual): January 28, 2015
• Study Completion (Actual): January 28, 2015

Study Registration Dates

• First Submitted: April 12, 2017
• First Submitted That Met QC Criteria: April 12, 2017
• First Posted (Actual): April 17, 2017

Study Record Updates

• Last Update Posted (Actual): April 17, 2017
• Last Update Submitted That Met QC Criteria: April 12, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antiparkinson Agents; Anti-Dyskinesia Agents; Catechol O-Methyltransferase Inhibitors; Opicapone
• Other Study ID Numbers: BIA-91067-128

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No