Single-dose Pharmacokinetics and Relative Bioavailability of Two Different Formulations of Opicapone

Phase 1

Completed

• Conditions: Parkinson Disease
• Interventions: Drug: BIA 9-1067 non-micronized; Drug: BIA 9-1067 micronized

• Registration Number: NCT02305316
• Lead Sponsor: Bial - Portela C S.A.

Brief Summary

Single-centre, open-label, randomised, two-way crossover study in 28 healthy volunteers. The study consisted of two consecutive single-dose treatment periods separated by a washout period of 14 days or more.

Detailed Description

Single-centre, open-label, randomised, two-way crossover study in 28 healthy volunteers. The study consisted of two consecutive single-dose treatment periods separated by a washout period of 14 days or more. A total of twenty-eight (28) healthy volunteers received a single dose of 50 mg OPC, orally.

Study Timeline

• Study Start: 2014-02
• Primary Completion: 2014-03
• Study Completion: 2014-03
• 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: All
• Target Recruitment: 28

Inclusion Criteria

• A signed and dated informed consent form (ICF) before any study-specific screening procedure was performed,
• 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 electrocardiogram (ECG),
• Negative tests for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibodies and anti-human immunodeficiency virus (HIV) antibodies at screening,
• Clinical laboratory test results clinically acceptable at screening and on D-1 of each treatment period,
• Negative screen for alcohol and drugs of abuse at screening and on D-1 of each treatment period,
• Non-smokers or ex-smokers for at least 3 months,
• Volunteer able to participate, and willing to give written informed consent and comply with the study restrictions,

If female:

• Was not of childbearing potential by reason of surgery or, if of childbearing potential, 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 was the sole partner of that subject) for the entire duration of the study,
• Negative serum pregnancy test at screening and a negative urine pregnancy test on D-1 of each treatment period.

Exclusion Criteria

• Any 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,
• Any clinically relevant abnormality in the coagulation tests,
• Any clinically relevant abnormality in the liver function tests,
• History of relevant atopy or drug hypersensitivity,
• History of alcoholism and/or drug abuse,
• Current consumption of 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°)],
• Any significant infection or known inflammatory process on screening or admission to each treatment period,
• Any acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to each treatment period,
• Use of medicines within 2 weeks of admission to first period that could affect the subject's safety or other study assessments, in the investigator's opinion,
• Previously received opicapone,
• Involvement in other clinical trials of any type within 90 days prior to screening,
• Participation in more than 2 clinical trials within the 12 months prior to screening,
• Blood donation or received any blood transfusion or any blood products within the 3 months prior to screening,
• Vegetarian, vegan or had medical dietary restrictions,
• Subject not able to communicate reliably with the investigator,
• Subjects who were unlikely to co-operate with the requirements of the study,
• Subjects who were unwilling or unable to give written informed consent,

If female:

• Pregnant or breast-feeding,
• If of childbearing potential, a positive serum pregnancy test,
• Volunteer who did not use an accepted effective contraceptive method or used oral contraceptives,

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
BIA 9-1067 non-micronized - micronized	BIA 9-1067 non-micronized	Each subject was orally administered with 50 mg OPC non-micronized followed by a washout period of 14 days. After washout period each subject was orally administered with 50 mg OPC micronized
BIA 9-1067 non-micronized - micronized	BIA 9-1067 micronized	Each subject was orally administered with 50 mg OPC non-micronized followed by a washout period of 14 days. After washout period each subject was orally administered with 50 mg OPC micronized
BIA 9-1067 micronized - non-micronized	BIA 9-1067 non-micronized	Each subject was orally administered 50 mg OPC micronized followed by a washout period of 14 days. After washout period each subject was orally administered with 50 mg OPC non-micronized
BIA 9-1067 micronized - non-micronized	BIA 9-1067 micronized	Each subject was orally administered 50 mg OPC micronized followed by a washout period of 14 days. After washout period each subject was orally administered with 50 mg OPC non-micronized

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration	before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose.	AUC0-t - Area under the plasma concentration-time curve from time 0 to the time of last quantifiable concentration of BIA 9-1067
Tmax - Time of Occurrence of Cmax of BIA 9-1067	before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose.	tmax - time of occurrence of maximum observed plasma concentration of BIA 9-1067
AUC0-inf - Area Under the Plasma Concentration-time Curve From Time 0 to the Infinity	before OPC dosing, and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose.	AUC0-inf - Area under the plasma concentration-time curve from time 0 to the infinity.