A Double-blind, Randomised, Placebo-controlled, Rising Multiple Dose Study to Investigate the Safety, Tolerability, Steady State Pharmacokinetic Profile and CNS Effects of BIA 2-093

Phase 1

Completed

Conditions: Epilepsy

Interventions: Drug: Placebo
Drug: BIA 2-093

Registration Number: NCT02171234

Lead Sponsor: Bial - Portela C S.A.

Brief Summary: The purpose of this study is to investigate the safety and tolerability of multiple dose regimens of BIA 2-093 in healthy young male volunteers

Detailed Description: Single centre, Phase I, double-blind, randomised, placebo-controlled study investigating 4 multiple rising oral doses of BIA 2-093 in 4 groups of 8 young healthy male subjects. Within each group, 2 subjects were randomised to receive placebo and the remaining 6 subjects to receive BIA 2-093. No subject was a member of more than one group. The dose regimens investigated were: 200 mg b.i.d.(twice daily), 400 mg o.d.(once daily; this was changed from 400 mg b.i.d. in protocol amendment 1, on the basis of interim pharmacokinetic analysis of Group 1 data), 800 mg o.d, and 1200 mg o.d. BIA 2-093/placebo was administered orally once daily on Days 1-8, or twice a day (at 12-hour intervals) on Days 1-7 with a final dose in the morning of Day 8. The multiple dose regimens were to be investigated in ascending order. Progression to each higher dose level was only to occur if the previous dose level was deemed by the investigator and the sponsor to be safe and well tolerated.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 32

Inclusion Criteria

Adult males aged 18-45 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, 12-lead ECG and EEG.
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 previous smokers who had not smoked for at least 6 months.
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 (carbamazepine and
related compounds).
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 dosing.
Subjects who had used any investigational drug and/or participated in any clinical trial within 3 months of admission to this study.
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.
Subjects who had previously received BIA 2-093.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 2 - 400 mg b.i.d.	BIA 2-093	BIA 2-093 200mg with 200 ml potable water. Identical placebo administered as oral tablets.
Group 3- 800 mg o.d. (once daily)	BIA 2-093	BIA 2-093 200mg with 200 ml potable water. Identical placebo administered as oral tablets.
Group 4 - either 800 mg b.i.d or 1200 mg o.d.	BIA 2-093	BIA 2-093 200mg with 200 ml potable water. Identical placebo administered as oral tablets.
Group 1- 200 mg b.i.d. (twice daily)	Placebo	BIA 2-093 200mg with 200 ml potable water. Identical placebo administered as oral tablets.
Group 3- 800 mg o.d. (once daily)	Placebo	BIA 2-093 200mg with 200 ml potable water. Identical placebo administered as oral tablets.
Group 2 - 400 mg b.i.d.	Placebo	BIA 2-093 200mg with 200 ml potable water. Identical placebo administered as oral tablets.
Group 4 - either 800 mg b.i.d or 1200 mg o.d.	Placebo	BIA 2-093 200mg with 200 ml potable water. Identical placebo administered as oral tablets.
Group 1- 200 mg b.i.d. (twice daily)	BIA 2-093	BIA 2-093 200mg with 200 ml potable water. Identical placebo administered as oral tablets.

Primary Outcome Measures

Name	Time	Method
Total Number of Adverse Events	up to 20 weeks	Total Number of Adverse Events.

Secondary Outcome Measures

Name	Time	Method
Cmax	Day 1 and Day 8	Cmax - Maximum observed plasma concentration
AUC0-τ	Day 1 - pre-dose, 30, 60, 90, 120, 180 minutes, 4, 6, 7, 8, 12, hours post final dose Day 8 - pre-dose, 30, 60, 90, 120, 180 minutes, 4, 6, 7, 8, 12, 24, 36, 48 and 72 hours post final dose	AUC0-τ - Area under the plasma concentration time curve to last measurable time point Day 1 - pre-dose, 30, 60, 90, 120, 180 minutes, 4, 6, 7, 8, 12, hours post final dose Day 8 - pre-dose, 30, 60, 90, 120, 180 minutes, 4, 6, 7, 8, 12, 24, 36, 48 and 72 hours post final dose