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

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, in Young Healthy Male Volunteers.

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

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Placebo; Drug: BIA 2-093

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 1YR
    • Guy's Drug Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1- 200 mg b.i.d. (twice daily); BIA 2-093 200mg with 200 ml potable water. Identical placebo administered as oral tablets.	Drug: Placebo; Other Names: PLC, Placebo; Drug: BIA 2-093; Other Names: ESL, Eslicarbazepine acetate
Experimental: Group 2 - 400 mg b.i.d.; BIA 2-093 200mg with 200 ml potable water. Identical placebo administered as oral tablets.	Drug: Placebo; Other Names: PLC, Placebo; Drug: BIA 2-093; Other Names: ESL, Eslicarbazepine acetate
Experimental: Group 3- 800 mg o.d. (once daily); BIA 2-093 200mg with 200 ml potable water. Identical placebo administered as oral tablets.	Drug: Placebo; Other Names: PLC, Placebo; Drug: BIA 2-093; Other Names: ESL, Eslicarbazepine acetate
Experimental: Group 4 - either 800 mg b.i.d or 1200 mg o.d.; BIA 2-093 200mg with 200 ml potable water. Identical placebo administered as oral tablets.	Drug: Placebo; Other Names: PLC, Placebo; Drug: BIA 2-093; Other Names: ESL, Eslicarbazepine acetate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Number of Adverse Events	Total Number of Adverse Events.	up to 20 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Cmax - Maximum observed plasma concentration	Day 1 and Day 8
AUC0-τ	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	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

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.

Study record dates

Study Major Dates

• Study Start: February 1, 2001
• Primary Completion (Actual): June 1, 2001
• Study Completion (Actual): June 1, 2001

Study Registration Dates

• First Submitted: June 20, 2014
• First Submitted That Met QC Criteria: June 20, 2014
• First Posted (Estimate): June 24, 2014

Study Record Updates

• Last Update Posted (Estimate): January 7, 2015
• Last Update Submitted That Met QC Criteria: December 19, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Epilepsy; BIA 2-093; Eslicarbazepine acetate
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Eslicarbazepine acetate
• Other Study ID Numbers: BIA-2093-102