Relative Bioavailability and Bioequivalence Of Different Formulations of Opicapone in Healthy Volunteers

Single-centre, open-label, randomised, three-part, two-way crossover study in 84 healthy volunteers. In each part, the study consisted of two consecutive single-dose treatment periods separated by a washout period of at least 14 days.

Study Overview

• Status: Completed
• Conditions: Parkinson
• Intervention / Treatment: Drug: BIA 9-1067 (clinical micronized, CM); Drug: BIA 9-1067 (to-be-marketed, TBM)

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A signed and dated informed consent form before any study-specific screening procedure was performed;
• Male or female subjects aged 18 to 45 years, inclusive;
• Body mass index (BMI) between 18 and 30 kg/m2 inclusive;
• Healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead electrocardiogram (ECG);
• Negative tests for hepatitis B surface antigen (HBsAg), anti- hepatitis C virus antibodies (HCV Ab) and anti-human immunodeficiency virus antibodies (HIV-1 and HIV-2 Ab) at screening;
• Clinical laboratory test results clinically acceptable at screening and admission to each treatment period;
• Negative screen for alcohol and drugs of abuse at screening and admission to each treatment period;
• Non-smokers or ex-smokers for at least 3 months;
• Able to participate, and willing to give written informed consent and comply with the study restrictions.
• If female:
• She was not of childbearing potential by reason of surgery or, if of childbearing potential, she used 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 was the sole partner of that subject] for all the duration of the study;
• She had a negative serum pregnancy test at screening and a negative urine pregnancy test at admission to each treatment period.

Exclusion Criteria:

• Subjects who had 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, or had a clinically relevant surgical history;
• Had clinically relevant findings in laboratory tests, particularly any abnormality in the coagulation tests, or any abnormality in the liver function tests;
• Had a history of relevant atopy or drug hypersensitivity;
• Had a history of alcoholism and/or drug abuse;
• Consumed more than 14 units of alcohol per week [1 unit of alcohol = 280 mL beer (3-4°) = 100 mL wine (10-12°) = 30 mL spirits (40°)];
• Had a significant infection or known inflammatory process on screening or admission to each treatment period;
• Had acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to each treatment period;
• Had used medicines within 2 weeks of admission to first period that could affect the safety or other study assessments, in the Investigator's opinion;
• Had previously received opicapone;
• Had used any investigational drug or participated in any clinical trial within 90 days prior to screening;
• Had participated in more than 2 clinical trials within the 12 months prior to screening;
• Had donated or received any blood or blood products within the 3 months prior to screening;
• Were vegetarians, vegans or had medical dietary restrictions;
• Could not communicate reliably with the Investigator;
• Were unlikely to co-operate with the requirements of the study;
• Were unwilling or unable to give written informed consent;

If female:

• She was pregnant or breast-feeding.

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

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIA 9-1067 5 mg Sequence 1; volunteers received a single oral dose of 5 mg BIA 9-1067: Period 1: CM Formulation Period 2: TBM Formulation CM - clinical micronized TBM - to-be-marketed	Drug: BIA 9-1067 (clinical micronized, CM); Other Names: OPC, Opicapone; Drug: BIA 9-1067 (to-be-marketed, TBM); Other Names: OPC, Opicapone
Experimental: BIA 9-1067 25 mg Sequence 1; volunteers received a single oral dose of 25 mg BIA 9-1067: Period 1: CM Formulation Period 2: TBM Formulation CM - clinical micronized TBM - to-be-marketed	Drug: BIA 9-1067 (clinical micronized, CM); Other Names: OPC, Opicapone; Drug: BIA 9-1067 (to-be-marketed, TBM); Other Names: OPC, Opicapone
Experimental: BIA 9-1067 50 mg Sequence 1; volunteers received a single oral dose of 50 mg BIA 9-1067: Period 1: CM Formulation Period 2: TBM Formulation CM - clinical micronized TBM - to-be-marketed	Drug: BIA 9-1067 (clinical micronized, CM); Other Names: OPC, Opicapone; Drug: BIA 9-1067 (to-be-marketed, TBM); Other Names: OPC, Opicapone
Experimental: BIA 9-1067 5 mg Sequence 2; volunteers received a single oral dose of 5 mg BIA 9-1067: Period 1: TBM Formulation Period 2: CM Formulation CM - clinical micronized TBM - to-be-marketed	Drug: BIA 9-1067 (clinical micronized, CM); Other Names: OPC, Opicapone; Drug: BIA 9-1067 (to-be-marketed, TBM); Other Names: OPC, Opicapone
Experimental: BIA 9-1067 25 mg Sequence 2; volunteers received a single oral dose of 25 mg BIA 9-1067: Period 1: TBM Formulation Period 2: CM Formulation CM - clinical micronized TBM - to-be-marketed	Drug: BIA 9-1067 (clinical micronized, CM); Other Names: OPC, Opicapone; Drug: BIA 9-1067 (to-be-marketed, TBM); Other Names: OPC, Opicapone
Experimental: BIA 9-1067 50 mg Sequence 2; volunteers received a single oral dose of 50 mg BIA 9-1067: Period 1: TBM Formulation Period 2: CM Formulation CM - clinical micronized TBM - to-be-marketed	Drug: BIA 9-1067 (clinical micronized, CM); Other Names: OPC, Opicapone; Drug: BIA 9-1067 (to-be-marketed, TBM); Other Names: OPC, Opicapone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax - Maximum Observed Plasma Concentration	before OPC dosing, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-t - Area Under the Plasma Concentration-time Curve for BIA 9-1067	Area Under the plasma concentration-time Curve from time 0 to the time of last quantifiable concentration	before OPC dosing, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose
Tmax - Time of Occurrence of Cmax		before OPC dosing, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: November 28, 2014
• First Submitted That Met QC Criteria: November 28, 2014
• First Posted (Estimate): December 2, 2014

Study Record Updates

• Last Update Posted (Estimate): November 17, 2015
• Last Update Submitted That Met QC Criteria: October 14, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antiparkinson Agents; Anti-Dyskinesia Agents; Catechol O-Methyltransferase Inhibitors; Opicapone
• Other Study ID Numbers: BIA-91067-119