Dosage Form Proportionality of Opicapone To-Be-Marketed Formulation

Phase 1

Completed

• Conditions: Epilepsy
• Interventions: Drug: BIA 9-1067

• Registration Number: NCT02305329
• Lead Sponsor: Bial - Portela C S.A.

Brief Summary

Single-centre, open-label, randomized, two-sequence, two-way crossover study. The study consisted of two consecutive single-dose treatment periods separated by a washout period of 10 to 14 days or more.

Detailed Description

Single-centre, open-label, randomized, two-sequence, two-way crossover study. The study consisted of two consecutive single-dose treatment periods separated by a washout period of 10 to 14 days or more. In Group 1 the volunteers received a single oral dose of 25 mg OPC. In Group 2 the volunteers received a single oral dose of 50 mg OPC

Study Timeline

• Study Start: 2014-02
• Primary Completion: 2014-04
• Study Completion: 2014-04
• Study First Submitted: 2014-11-28
• Study First Submitted QC: 2014-11-28
• Study First Posted: 2014-12-02
• Status Verified: 2015-07
• Results First Submitted: 2015-07-22
• Results First Submitted QC: 2015-07-22
• Last Update Submitted: 2015-07-22
• Results First Posted: 2015-08-21
• Last Update Posted: 2015-08-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 56

Inclusion Criteria

• Male or female subjects aged 18 to 45 years, inclusive;
• Body mass index (BMI) between 19 and 30 kg/m²;
• Healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination, and 12-lead ECG; - Negative tests for hepatitis B surface antigen (HBsAg), anti-hepatitis C vírus (anti-HCV) antibodies, and anti-human immunodeficiency virus (HIV)-1/-2 antibodies 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 and willing to give written informed consent;
• If female: She was not of childbearing potential by reason of surgery or, if of childbearing potential, she used an effective nonhormonal 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; and she had a negative serum pregnancy test at screening and a negative urine pregnancy test on Day -1 of each treatment period.

Exclusion Criteria

• 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;
• A clinically relevant surgical history;
• Any clinically relevant abnormality in the coagulation tests;
• Any clinically relevant abnormality in the liver function tests. If the subject had a borderline clinically relevant abnormality that was not considered clinically significant, a retest could be done after discussion with the sponsor's medical monitor;
• A history of relevant atopy or drug hypersensitivity;
• A history of alcoholism or drug abuse;
• Consume more than 14 units of alcohol a week;
• A significant infection or known inflammatory process on screening or admission to each treatment period;
• Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to each treatment period;
• Used medicines within 2 weeks of admission to first period that could have affected the subject's safety or other study assessments in the investigator's opinion;
• Previously received OPC. Previous use of OPC was documented by questioning the subjects;
• 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;
• Not able to communicate reliably with the investigator;
• Unlikely to co-operate with the requirements of the study; unwilling or unable to give written informed consent;
• If female: she was pregnant or breast-feeding; she had a positive serum pregnancy test; she was of childbearing potential and did not use an accepted effective contraceptive method or she used oral contraceptives.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Group 1 BIA 9-1067 50 mg	BIA 9-1067	Period 1 - 2x25 mg OPC Period 2 - 1x50 mg OPC
Group 1 BIA 9-1067 25 mg	BIA 9-1067	Period 1 - 5x5 mg OPC Period 2 - 1x25 mg OPC
Group 2 BIA 9-1067 50 mg	BIA 9-1067	Period 1 - 1x50 mg OPC Period 2 - 2x25 mg OPC
Group 2 BIA 9-1067 25 mg	BIA 9-1067	Period 1 - 1x25 mg OPC Period 2 - 5x5 mg OPC

Primary Outcome Measures

Name	Time	Method
Cmax - Maximum Observed Plasma Concentration of 9-1067	before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48h post-OPC dose	Cmax - maximum observed plasma concentration of 9-1067.

Secondary Outcome Measures

Name	Time	Method
AUC0-t - Area Under the Plasma Concentration-time Curve Calculated Between Time of Administration and Time t	before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48h post-OPC dose
Tmax - Time of Occurrence of Cmax of 9-1067	before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48h post-OPC dose	tmax - time of occurrence of Maximum Observed Plasma Concentration of 9-1067
AUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity	before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48h post-OPC dose	AUC0-∞ - Area under the plasma concentration-time curve extrapolated to infinity.