Study to Investigate the Safety, Tolerability, Steady State Pharmacokinetic and Pharmacodynamic Profile of BIA 3-202

Study Overview
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Brief Summary
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The objectives as stated in the study protocol were as follows: To investigate the safety and tolerability of three multiple dose regimens of BIA 3-202 (50 mg twice a day, 100 mg twice a day and 200 mg twice a day in healthy young male volunteers). Part A To characterise the steady state pharmacokinetic and pharmacodynamic profile of BIA 3-202 in healthy young males. Part A To investigate the safety and tolerability of a single multiple dose regimen (dose to be determined from Part A) of BIA 3-202, in healthy elderly volunteers. Part B To characterise the steady state pharmacokinetic and pharmacodynamic profile of a single multiple dose regimen (dose to be determined from Part A) of BIA 3- 202 in healthy elderly volunteers. Part B

Detailed Description
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This was designed as a single centre, phase I, double-blind, randomised, placebocontrolled study of three multiple rising doses in three sequential groups of 8 young male healthy volunteers (Part A) and a single group of healthy elderly volunteers (Part B). In Part B, 12 healthy elderly volunteers were to be enrolled. Ten were to be randomly allocated to BIA 3-202 and two to placebo.

Official Title
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Double-Blind, Randomised, Placebo-Controlled, Rising Multiple Dose Study to Investigate the Safety, Tolerability, Steady State Pharmacokinetic and Pharmacodynamic Profile of BIA 3-202, in Young Healthy Volunteers

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: BIA 3-202
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult males aged 18-35 years, with a body mass index (BMI) of 19-28 kg/m2. Subjects who were healthy as determined by pre-study medical history, physical examination and 12-lead ECG. Subjects who had clinical laboratory tests acceptable to the investigator. Subjects who were negative for HbsAg, anti-HCV and HIV I and II tests at screening. Subjects who were negative for drugs of abuse and alcohol tests at screening and admission. Subjects who were non-smokers or who smoked less than 10 cigarettes or equivalent per day. Subjects who were able and willing to give written informed consent. Exclusion Criteria: Subjects who did not conform to the above inclusion criteria. Subjects who had a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders. Subjects who had a clinically relevant surgical history. Subjects who had a clinically relevant family history. Subjects who had a history of relevant atopy. Subjects who had a history of relevant drug hypersensitivity. Subjects who had a history of alcoholism. Subjects who had a history of drug abuse. Subjects who consumed more than 28 units of alcohol a week. Subjects who had a significant infection or known inflammatory process on screening and/or admission. Subjects who had acute gastrointestinal symptoms at the time of screening and/or admission (e.g. nausea, vomiting, diarrhoea, heartburn). Subjects who had an acute infection such as influenza at the time of screening and/or admission. Subjects who had used prescription drugs within 4 weeks of first dosing. Subjects who had used over the counter medication, excluding routine vitamins but including mega dose vitamin therapy, within one week of first dosing. Subjects who had used any investigational drug and/or participated in any clinical trial within 3 months of their first admission to this study. Subjects who had previously received BIA 3-202. Subjects who had donated and/or received any blood or blood products within 3 months prior to screening. Subjects who were vegetarians, vegans and/or had medical dietary restrictions. Subjects who could not 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

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 |
| --- | --- |
| Experimental: Group 1: BIA 3-202 50 mg/placebo<br>Group 1: BIA 3-202 50 mg/placebo on Day 1; BIA 3-202 50 mg/placebo b.i.d. on Days 3-8 inclusively; final single dose of BIA 3-202 50 mg/placebo on Day 9. 50 mg BIA 3-202: 5 x 10 mg BIA 3-202 tablets | Drug: BIA 3-202<br>* BIA 3-202 (50, 100 and 200 mg) was administered in the form of oral tablets, given with 200 ml potable water.<br>Drug: Placebo<br>* Matched placebo was administered in the form of oral tablets, given with 200 ml potable water<br>|
| Experimental: Group 2: BIA 3-202 100 mg/placebo<br>Group 2: BIA 3-202 100 mg/placebo on Day 1; BIA 3-202 100 mg/placebo b.i.d. on Days 3-8 inclusively; final single dose of BIA 3-202 100 mg/placebo on Day 9. 100 mg BIA 3-202: 1 x 100 mg BIA 3-202 tablet | Drug: BIA 3-202<br>* BIA 3-202 (50, 100 and 200 mg) was administered in the form of oral tablets, given with 200 ml potable water.<br>Drug: Placebo<br>* Matched placebo was administered in the form of oral tablets, given with 200 ml potable water<br>|
| Experimental: Group 3: BIA 3-202 200 mg/placebo<br>Group 3: BIA 3-202 200 mg/placebo on Day 1; BIA 3-202 200 mg/placebo b.i.d. on Days 3-8 inclusively; final single dose of BIA 3-202 200 mg/placebo on Day 9. 200 mg BIA 3-202: 2 x 100 mg BIA 3-202 tablets | Drug: BIA 3-202<br>* BIA 3-202 (50, 100 and 200 mg) was administered in the form of oral tablets, given with 200 ml potable water.<br>Drug: Placebo<br>* Matched placebo was administered in the form of oral tablets, given with 200 ml potable water<br>|
| Experimental: Group 4: BIA 3-202 200 mg/placebo<br>Group 4: BIA 3-202 200 mg/placebo on Day 1; BIA 3-202 200 mg/placebo t.i.d. on Days 3-8 inclusively; final single dose of BIA 3-202 200 mg/placebo on Day 9. 200 mg BIA 3-202: 2 x 100 mg BIA 3-202 tablets | Drug: BIA 3-202<br>* BIA 3-202 (50, 100 and 200 mg) was administered in the form of oral tablets, given with 200 ml potable water.<br>Drug: Placebo<br>* Matched placebo was administered in the form of oral tablets, given with 200 ml potable water<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) - D1 |  | Day 1 | 
| Time of maximum observed concentration (tmax) - D1 |  | Day 1 | 
| Area under the plasma concentration time curve to last measurable time point (AUC0-t) - D1 |  | Day 1 | 
| Area under the plasma concentration time curve extrapolated to infinity (AUC0-∞) - D1 |  | Day 1 | 
| Maximum observed plasma concentration (Cmax) - D9 |  | Day 9 | 
| Time of maximum observed concentration (tmax) - D9 |  | Day 9 | 
| Area under the plasma concentration time curve to last measurable time point (AUC0-t) - D9 |  | Day 9 | 
| Area under the plasma concentration time curve extrapolated to infinity (AUC0-∞) - D9 |  | Day 9 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, Nebicapone