Study of BIA 9-1067 to Investigate Its Effect on Levodopa Pharmacokinetic

Study Overview
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Brief Summary
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To investigate the effect of repeated dosing of BIA 9-1067 on the levodopa pharmacokinetics, in comparison to placebo and entacapone.

Detailed Description
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Single-centre, double-blind, randomised, parallel-group study in 80 young male and female healthy subjects.

Official Title
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A Double-blind, Randomised, Placebo- and Active-controlled Multiple-dose Study of BIA 9-1067 to Investigate Its Effect on Levodopa Pharmacokinetics Following a Levodopa/Carbidopa 100/25 mg Single-dose in Healthy Subjects

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: BIA 9-1067 5 mg
* Drug: Entacapone
* Drug: Placebo
* Drug: levodopa/carbidopa
* Drug: BIA 9-1067 15 mg
* Drug: BIA 9-1067 30 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to give written informed consent. Male or female subjects aged between 18 and 45 years, inclusive. Subjects of body mass index (BMI) between 19 and 30 kg/m2, inclusive. Healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG. Negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab at screening. Clinical laboratory test results clinically acceptable at screening and admission to the treatment period. Negative screen for alcohol and drugs of abuse at screening and admission to the treatment period. Non-smokers or ex-smokers for at least 3 months. (If female) She was not of childbearing potential by reason of surgery or, if of childbearing potential, she used one of the following methods of contraception: intrauterine device (by the subject) and condoms (by the partner) or diaphragm (by the subject) and condoms (by the partner) or spermicide (by the subject) and condoms (by the partner). (If female) She had a negative urine pregnancy test at screening and admission to the treatment period. Exclusion Criteria: 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. Clinically relevant surgical history. Any abnormality in the coagulation tests. Any abnormality in the liver function tests. A history of relevant atopy or drug hypersensitivity. A history or presence of narrow-angle glaucoma. A suspicious undiagnosed skin lesions or a history of melanoma. History of alcoholism or drug abuse. Consumed more than 14 units of alcohol a week. Significant infection or known inflammatory process at screening or admission to the treatment period. Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to the treatment period. Had used non-selective monoamine oxidase (MAO) inhibitors within 2 weeks of admission to the treatment period. Had used medicines within 2 weeks of admission to the treatment period that may have affected the safety or other study assessments, in the investigator's opinion. Had previously received BIA 9-1067. Had used any investigational drug or participated in any clinical trial within 6 months 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. Vegetarians, vegans or had medical dietary restrictions. Cannot communicate reliably with the investigator. Unlikely to co-operate with the requirements of the study. Unwilling or unable to gave written informed consent. (If female) She was pregnant or breast-feeding. (If female) She was of childbearing potential and she did not use an approved effective contraceptive method or she used oral contraceptives.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group 1<br>Placebo at all the dosing times | Drug: Placebo<br>* placebo (four times a day)<br>* Other names: PLC, placebo;|
| Experimental: Group 2<br>Day 1 to 7: BIA 9-1067 5 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose Day 8: BIA 9-1067 5 mg: 7 AM dose Placebo+ levodopa/carbidopa 100/25 mg: 8 AM dose | Drug: BIA 9-1067 5 mg<br>* BIA 9-1067 OPC, Opicapone 5 mg<br>* Other names: OPC, Opicapone;Drug: Placebo<br>* placebo (four times a day)<br>* Other names: PLC, placebo;Drug: levodopa/carbidopa<br>* standard release levodopa/carbidopa 100/25 mg (single-dose)<br>|
| Experimental: Group 3<br>Day 1 to 7: BIA 9-1067 15 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose Day 8: BIA 9-1067 15 mg: 7 AM dose Placebo+ levodopa/carbidopa 100/25 mg: 8 AM dose | Drug: Placebo<br>* placebo (four times a day)<br>* Other names: PLC, placebo;Drug: levodopa/carbidopa<br>* standard release levodopa/carbidopa 100/25 mg (single-dose)<br>Drug: BIA 9-1067 15 mg<br>* BIA 9-1067 OPC, Opicapone 15 mg<br>* Other names: OPC, Opicapone;|
| Experimental: Group 4<br>Day 1 to 7: BIA 9-1067 30 mg: 7 AM dose Placebo: 8 AM; 4 PM; 12 PM dose Day 8: BIA 9-1067 30 mg: 7 AM dose Placebo + levodopa/carbidopa 100/25 mg: 8 AM dose | Drug: Placebo<br>* placebo (four times a day)<br>* Other names: PLC, placebo;Drug: levodopa/carbidopa<br>* standard release levodopa/carbidopa 100/25 mg (single-dose)<br>Drug: BIA 9-1067 30 mg<br>* BIA 9-1067 OPC, Opicapone 30 mg<br>* Other names: OPC, Opicapone;|
| Experimental: Group 5<br>Day 1 to 7: Placebo: 7 AM dose; Entacapone 200 mg: 8 AM; 4 PM; 12 PM dose Day 8: Placebo: 7 AM dose Entacapone 200 mg + levodopa/carbidopa 100/25 mg: 8 AM dose | Drug: Entacapone<br>* Entacapone 200 mg<br>Drug: Placebo<br>* placebo (four times a day)<br>* Other names: PLC, placebo;Drug: levodopa/carbidopa<br>* standard release levodopa/carbidopa 100/25 mg (single-dose)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax - Maximum Plasma Concentration of Levodopa | Cmax - Maximum plasma concentration of levodopa following a single oral administration of Sinemet® 100/25 on Day 8, and 5 mg, 15 mg and 30 mg BIA 9-1067 once-daily (QD), 200 mg entacapone thrice-daily (TID), and placebo, for 8 days | 8 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax - Time to Reach Maximum Plasma Concentration of Levodopa | Tmax - Time to Reach maximum plasma concentration of levodopa following a single oral administration of Sinemet® 100/25 on Day 8, and 5 mg, 15 mg and 30 mg BIA 9-1067 once-daily (QD), 200 mg entacapone thrice-daily (TID), and placebo, for 8 days. | 8 days | 
| AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification. | AUC0-t - Area under the plasma concentration-time curve (AUC) of levodopa from time zero to the last sampling time following a single oral administration of Sinemet® 100/25 on Day 8, and 5 mg, 15 mg and 30 mg BIA 9-1067 once-daily (QD), 200 mg entacapone thrice-daily (TID), and placebo, for 8 days | 8 days | 
| AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity | AUC0-∞ - Area under the plasma concentration-time curve (AUC) of levodopa from time zero to infinity. | 8 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson Disease, BIA 9-1067