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

Study Overview
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Brief Summary
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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.

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

Conditions
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Parkinson

Intervention / Treatment
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* Drug: BIA 9-1067 (clinical micronized, CM)
* Drug: BIA 9-1067 (to-be-marketed, TBM)


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIA 9-1067 5 mg Sequence 1<br>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)<br> <br> * Other names: OPC, Opicapone;Drug: BIA 9-1067 (to-be-marketed, TBM)<br> <br> * Other names: OPC, Opicapone;|
| Experimental: BIA 9-1067 25 mg Sequence 1<br>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)<br> <br> * Other names: OPC, Opicapone;Drug: BIA 9-1067 (to-be-marketed, TBM)<br> <br> * Other names: OPC, Opicapone;|
| Experimental: BIA 9-1067 50 mg Sequence 1<br>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)<br> <br> * Other names: OPC, Opicapone;Drug: BIA 9-1067 (to-be-marketed, TBM)<br> <br> * Other names: OPC, Opicapone;|
| Experimental: BIA 9-1067 5 mg Sequence 2<br>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)<br> <br> * Other names: OPC, Opicapone;Drug: BIA 9-1067 (to-be-marketed, TBM)<br> <br> * Other names: OPC, Opicapone;|
| Experimental: BIA 9-1067 25 mg Sequence 2<br>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)<br> <br> * Other names: OPC, Opicapone;Drug: BIA 9-1067 (to-be-marketed, TBM)<br> <br> * Other names: OPC, Opicapone;|
| Experimental: BIA 9-1067 50 mg Sequence 2<br>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)<br> <br> * Other names: OPC, Opicapone;Drug: BIA 9-1067 (to-be-marketed, TBM)<br> <br> * Other names: OPC, Opicapone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |