A Study to Evaluate the Tolerability and Pharmacokinetics of Two Single and Multiple High Dose Regimens of BIA 2-093 In Healthy Volunteers

Phase 1

Completed

Conditions: Epilepsy

Interventions: Drug: BIA 2-093 - 1800 mg (Group 1)
Drug: Placebo
Drug: BIA 2-093 - 2400 mg (Group 2)

Registration Number: NCT01879345

Lead Sponsor: Bial - Portela C S.A.

Brief Summary: Single centre, double-blind, randomised, placebo-controlled study of two dosage regimens of BIA 2-093 - 1800 mg (Group 1) and 2400 mg (Group 2) - in two groups of healthy male volunteers

Detailed Description: Within each group (n=9) 3 volunteers were randomised to receive placebo and the remaining 6 volunteers to receive BIA 2-093. No volunteer was a member of more than one treatment group. In each group, the study consisted of a single-dose period (Phase A) followed by a 7-day multiple-dose period (Phase B). The multiple-dose phase started 96 h post single-dose. Progression to the 2400 mg dose (Group 2) only occurred if the 1800 mg dose (Group 1) was considered to be safe and well tolerated. An appropriate interval separated the investigation of the two groups in order to permit a timely review and evaluation of safety data.

Treatment consisted of a single-dose (Phase A) followed by a once-daily dose for 7 days (Phase B). Doses were prepared as follows: Group 1 = 3 tablets of BIA 2-093 600 mg plus 1 placebo tablet, or 4 placebo tablets; Group 2 = 4 tablets of BIA 2-093 600 mg, or 4 placebo tablets.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 18

Inclusion Criteria

Male subjects aged between 18 and 45 years, inclusive.
Subjects of body mass index (BMI) between 19 and 30 kg/m2, inclusive.
Subjects who were healthy as determined by pre-study medical history, physical examination, vital signs, neurological examination, and 12-lead ECG.
Subjects who had clinical laboratory tests within normal ranges at screening and admission.
Subjects who had negative tests for HBsAg, anti-HCV Ab and HIV-1 and HIV-2 Ab at screening.
Subjects who were negative for drugs of abuse and alcohol at screening and admission.
Subjects who were non-smokers or 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, OR
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.
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 or drug abuse.
Subjects who consumed more than 14 units of alcohol a week.
Subjects who had a significant infection or known inflammatory process on screening or admission.
Subjects who had acute gastrointestinal symptoms at the time of screening or admission (e.g., nausea, vomiting, diarrhoea, heartburn).
Subjects who had used prescription or over-the-counter medication within 2 weeks of admission.
Subjects who had used any investigational drug or participated in any clinical trial within 3 months of admission.
Subjects who had previously received BIA 2-093.
Subjects who had donated or received any blood or blood products within the previous 3 months prior to screening.
Subjects who were vegetarians, vegans 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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BIA 2-093 - 1800 mg (Group 1)	BIA 2-093 - 1800 mg (Group 1)	3 tablets of BIA 2-093 600 mg
Placebo	Placebo	placebo tablets
BIA 2-093 - 2400 mg (Group 2)	BIA 2-093 - 2400 mg (Group 2)	4 tablets of BIA 2-093 600 mg

Primary Outcome Measures

Name	Time	Method
Number of Adverse Events Reported	3 weeks	investigate the tolerability of two single- and multiple-dose regimens of BIA 2-093 (1800 mg and 2400 mg)considering the Number of adverse events reported by patient

Secondary Outcome Measures

Name	Time	Method
Cmax - Maximum Observed Plasma Drug Concentration	Day 1 and Day 7	Single dose: pharmacokinetic parameters following an oral single-dose of BIA 2-093 Multiple dose: pharmacokinetic parameters following the last dose of an oral 7- day once-daily regimen of BIA 2-093 Oxcarbazepine is a BIA 2-093 metabolite
Tmax - the Time of Occurrence of Cmax	Day 1 and Day 7	Single dose: pharmacokinetic parameters following an oral single-dose of BIA 2-093 Multiple dose: pharmacokinetic parameters following the last dose of an oral 7- day once-daily regimen of BIA 2-093 Oxcarbazepine is a BIA 2-093 metabolite
AUC0-τ	Day 1 and Day 7	Single dose: pharmacokinetic parameters following an oral single-dose of BIA 2-093 Multiple dose: pharmacokinetic parameters following the last dose of an oral 7- day once-daily regimen of BIA 2-093 Oxcarbazepine is a BIA 2-093 metabolite