Relative Bioavailability and Bioequivalence of Opicapone

A Phase I, Open-Label, Randomised, Three-Period, Three-Sequence, Partial Replicate Crossover Study to Investigate the Relative Bioavailability and Bioequivalence of Opicapone Obtained From Two Different Sources, Under Fasting Conditions After Single-dose Administration in Healthy Subjects

the purpose assess the relative bioavailability and bioequivalence of two active pharmaceutical ingredient (API) sources of opicapone (OPC, Ongentys® and BIA 9-1067) following single 50 mg dose administration under fasting conditions in healthy volunteers

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Ongentys; Drug: BIA 9-1067 (test)

Detailed Description

This will be a Phase I, open label, randomized, partial-replicate, three-period, three-sequence crossover study to investigate the relative bioavailability and bioequivalence of 2 API sources of OPC (BIA 9-1067 [Test] and Ongentys® [Reference]) in healthy adult subjects.

Subjects will be randomized in a 3-period, 3-sequence crossover design; each subject will receive 2 single oral 50 mg doses of the Reference API source of OPC, and a single 50 mg dose of the Test API source of OPC under fasting conditions.

Potential subjects will be screened to assess their eligibility to enter the study within 28 days prior to the first dose administration. Subjects will be admitted into the Clinical Research Unit (CRU) on Day 1 and be confined to the CRU until discharge on Day 3. There will be a washout period of at least 14 days between each dose. A follow-up visit will be performed 7 to 14 days after dosing in the last treatment period or early discontinuation.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS2 9LH
    • Covance Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males or females, between 18 and 55 years of age, inclusive.
2. Body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive.
3. Healthy subjects as determined by no clinically significant findings from medical history, physical examination, complete neurological examination, 12 lead ECG, vital signs measurements, and clinical laboratory evaluations (congenital nonhaemolytic hyperbilirubinemia [eg, suspicion of Gilbert's syndrome based on total and direct bilirubin] is not acceptable) at Screening and Check in as assessed by the Investigator (or designee).
4. Females will not be pregnant (i.e. the the pregnancy test at screening and at admission to each treatment period must be negative), or lactating, and females of childbearing potential and males will agree to use contraception.
5. Able to comprehend and willing to sign and date an Informed Consent Form (ICF) before any study-specific screening procedure is performed, and to abide by the study restrictions.

Exclusion Criteria:

1. Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, haematological, lymphatic, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, genitourinary, immunological, connective tissue diseases or disorders, musculoskeletal, psychiatric disorder, or have a clinically relevant surgical history as determined by the Investigator (or designee).
2. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
3. History of febrile illness within 10 days prior to the each dose of study drug, or subjects with evidence of active infection
4. Acute gastrointestinal symptoms (eg nausea, vomiting, diarrhoea, heartburn) as determined by the Investigator (or designee).

5. Significantly impaired hepatic function, defined as any of the following (confirmed by repeat):

   1. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 x upper limit of normal (ULN)
   2. Total bilirubin (TBL) > 2 x ULN
6. Significant personal or family history of haemostatic disorders
7. History of galactose intolerance (eg the Lapp lactase deficiency or glucose-galactose malabsorption)
8. Symptomatic orthostatic hypotension (drop of > 20 mmHg in systolic blood pressure and/or > 10 mmHg in diastolic blood pressure) when moving from supine to standing position, together with other symptoms, e.g., dizziness.
9. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed).
10. History of alcoholism or drug/chemical abuse within 2 years prior to Check in to the first treatment period.
11. Alcohol consumption of >21 units per week for males and >14 units for females. One unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of spirits.
12. Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) at Screening or Check in to each treatment period.
13. Positive hepatitis panel and/or positive human immunodeficiency virus test
14. Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 90 days prior to first dose of study drug.
15. Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to Check-in of the first treatment period, unless deemed acceptable by the Investigator (or designee).
16. Use or intend to use any prescription medications/products within 14 days prior to dosing, unless deemed acceptable by the Investigator (or designee).
17. Use or intend to use slow release medications/products considered to still be active within 14 days prior to Check in, unless deemed acceptable by the Investigator (or designee).
18. Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant derived preparations within 7 days prior to Check in, unless deemed acceptable by the Investigator (or designee).
19. Use of tobacco or nicotine containing products within 3 months prior to Check in, or positive cotinine at Screening or Check-in.
20. Receipt of blood products within 2 months prior to Check in.
21. Donation of blood from 3 months prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.
22. Subjects who are vegetarians, vegans or have medical dietary restrictions
23. Poor peripheral venous access.
24. Have previously completed or withdrawn from this study or any other study investigating opicapone, and have previously received the investigational product.
25. Subjects who, in the opinion of the Investigator (or designee), should not participate in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: OPC, Ongentys; Single oral doses of 50 mg opicapone, administered using the reference (Ongentys ®) active pharmaceutical ingredient (API) source	Drug: Ongentys; single oral 50 mg (capsule containing 50 mg OPC) under fasting conditions
Experimental: BIA 9-1067; Single oral doses of 50 mg opicapone, administered using the test (BIA 9-1067)	Drug: BIA 9-1067 (test); single oral 50 mg (capsule containing 50 mg OPC) under fasting conditions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
area under the plasma concentration-time curve from time zero to infinity (AUC0 ∞)	PK parameters from Blood samples to be be collected for the analysis of plasma concentrations of opicapone.	Day 1 up to day 14
area under the plasma concentration-time curve from time zero to the last observable concentration at time t (AUC0 t)	PK parameters from Blood samples to be be collected for the analysis of plasma concentrations of opicapone.	Day 1 up to day 14
maximum observed plasma concentration (Cmax)	PK parameters from Blood samples to be be collected for the analysis of plasma concentrations of opicapone.	Day 1 up to day 14

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2019
• Primary Completion (Actual): June 9, 2019
• Study Completion (Actual): June 9, 2019

Study Registration Dates

• First Submitted: January 25, 2019
• First Submitted That Met QC Criteria: January 25, 2019
• First Posted (Actual): January 29, 2019

Study Record Updates

• Last Update Posted (Actual): December 31, 2020
• Last Update Submitted That Met QC Criteria: December 30, 2020
• Last Verified: December 1, 2020

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-91067-132

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