Single-dose and Steady-state Pharmacokinetics of BIA 2-093 and Its Metabolites

• ClinicalTrials.gov Identifier: NCT02172755
• Recruitment Status: Completed
• First Posted: June 24, 2014
• Results First Posted: December 31, 2014
• Last Update Posted: May 19, 2017
• Sponsor: Bial - Portela C S.A.
• Information provided by (Responsible Party): Bial - Portela C S.A.

Study Description

Brief Summary:

The purpose of this study is to determine the effects of age on the pharmacokinetic profile of BIA 2-093 and its active metabolites.

Condition or disease	Intervention/treatment	Phase
Epilepsy	Drug: BIA 2-093	Phase 1

Detailed Description:

This was a single-centre, open-label, parallel group, non-randomised study with a single-dose phase (Phase A) followed by a multiple-dose phase (Phase B), in 12 healthy elderly and 12 healthy young subjects. During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Single-dose and Steady-state Pharmacokinetics of BIA 2-093 and Its Metabolites in Healthy Elderly Subjects Compared With Those in Healthy Young Subjects
• Study Start Date: June 2002
• Actual Primary Completion Date: August 2002
• Actual Study Completion Date: August 2002

Arms and Interventions

Arm	Intervention/treatment
Experimental: Elderly subjects; 14 Elderly subjects aged 65 years or more; During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.	Drug: BIA 2-093; During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.; Other Name: Eslicarbazepine acetate
Experimental: Young subjects; 16 young subjects aged between 18 and 40 years During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.	Drug: BIA 2-093; During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.; Other Name: Eslicarbazepine acetate

Outcome Measures

Primary Outcome Measures :

1. Maximum Drug Concentration (Cmax) [ Time Frame: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose From Day 5 to Day 11 inclusive, before the daily dose (for trough levels). On Day 12, pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours p ]

   Single-dose period: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose.

   Multiple-dose period: from Day 5 to Day 11 inclusive, early in the morning, before the daily dose (for trough levels).

   Day 12: pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-last dose.

   BIA 2-194, BIA 2-195, and oxcarbazepine are metabolites of BIA 2-093

Secondary Outcome Measures :

1. Tmax - Time of Maximum Observed Concentration [ Time Frame: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose From Day 5 to Day 11 inclusive, before the daily dose (for trough levels). On Day 12, pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours p ]

   Single-dose period: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose.

   Multiple-dose period: from Day 5 to Day 11 inclusive, early in the morning, before the daily dose (for trough levels).

   Day 12: pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-last dose.

   BIA 2-194, BIA 2-195, and oxcarbazepine are metabolites of BIA 2-093

2. AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point [ Time Frame: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose From Day 5 to Day 11 inclusive, before the daily dose (for trough levels). On Day 12, pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours p ]

   Single-dose period: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose.

   Multiple-dose period: from Day 5 to Day 11 inclusive, early in the morning, before the daily dose (for trough levels).

   Day 12: pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-last dose.

   BIA 2-194, BIA 2-195, and oxcarbazepine are metabolites of BIA 2-093

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Male or female subjects aged between 18 and 40 years, inclusive OR male or female subjects aged 65 years or more.
• If young, subjects who were within 15% of ideal body weight OR, if elderly, subjects who were within 20% of ideal body weight according to the Metropolitan Life Insurance Table.
• Subjects who were healthy as determined by pre-study medical history, physical examination, neurological examination, and 12-lead ECG.
• Subjects who had clinical laboratory tests acceptable to the Investigator.
• Subjects who were negative for HBsAg, HCVAb and HIV-1 and HIV-2 Ab tests at screening.
• Subjects who were negative for alcohol and drugs of abuse at screening.
• 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.
• (If female) She was not of childbearing potential by reason of surgery or menopause or, if of childbearing potential, she used one of the following methods of contraception: double barrier or intrauterine.
• (If female and with less than 40 years old) She had a negative pregnancy test at screening.

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 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 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 used drugs within 2 weeks 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 2-093.
• Subjects who had donated and/or received any blood or blood products within the previous 2 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.
• (If female) She was pregnant or breast-feeding
• (If female) She was of childbearing potential and she did not use an authorised effective contraceptive method.

Contacts and Locations

Locations

Germany

Scope International Life Sciences AG,

Hamburg, Germany, D-22525

Sponsors and Collaborators

Bial - Portela C S.A.

More Information

• Responsible Party: Bial - Portela C S.A.
• ClinicalTrials.gov Identifier: NCT02172755
• Other Study ID Numbers: BIA-2093-105
• First Posted: June 24, 2014
• Results First Posted: December 31, 2014
• Last Update Posted: May 19, 2017
• Last Verified: April 2017

Keywords provided by Bial - Portela C S.A.:

Eslicarbazepine acetate; BIA 2-093

Additional relevant MeSH terms:

Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Eslicarbazepine acetate; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action