The Effect of BIA 2-093 on the Steady-state Pharmacokinetics of Digoxin

The Effect of BIA 2-093 on the Steady-state Pharmacokinetics of Digoxin in Healthy Volunteers

The purpose of this study is to investigate the effects of multiple-dose administration of BIA 2-093 on the steady-state pharmacokinetics of digoxin in healthy subjects.

Study Overview

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

Detailed Description

Single centre, multiple-dose, double-blind, randomised, placebo-controlled, two-way crossover study in 12 healthy volunteers. The study consisted of two 8-day treatment periods separated by a washout of 10 or more days. During each of the treatment periods the volunteers received either a daily oral dose of BIA 2-093 1200 mg once-daily (od) or matching placebo, concomitantly with a dose of digoxin (days 1 and 2: loading dose of 0.5 mg/day; days 3 to 8: 0.25 mg/day).

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• Portugal
  • Coronado (S.Romão E S. Mamede)
    • Trofa, Coronado (S.Romão E S. Mamede), Portugal
      • Human Pharmacology Unit (UFH)Section of Clinical Research (SIC), Department of Research & Development (DID), BIAL - Portela & Cª, SA,

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female subjects aged between 18 and 45 years, inclusive.
• Subjects of body mass index (BMI) between 19 and 28 kg/m2, inclusive.
• 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 clinically acceptable.
• Subjects who were negative for HBs Ag, anti-HCV Ab and anti-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.
• In case of female volunteers, subjects who were not of childbearing potential by reason of surgery or, if of childbearing potential, used one of the following methods of contraception: double-barrier or intrauterine device.
• In case of female volunteers, subjects who 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, 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 any of the following findings on the ECG: QTc interval >440 msec; first-, second- or third-degree atrioventricular block; atrial fibrillation; heart rate below 50 bpm; any other relevant abnormality.
• 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 prescription drugs within 4 weeks of first dosing.
• Subjects who had used over the counter medication excluding oral 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 2 months of their first admission.
• 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.
• In case of female volunteers, subjects who were pregnant or breast-feeding.
• In case of female volunteers, subjects who were of childbearing potential and did not use an authorized effective contraceptive method.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIA 2-093; BIA 2-093 1200 mg (2 tablets 600 mg) ESL, Eslicarbazepine acetate Concomitantly with a dose of digoxin (days 1 and 2: loading dose of 0.5 mg/day; days 3 to 8: 0.25 mg/day).	Drug: BIA 2-093; BIA 2-093 1200 mg once-daily; Other Names: ESL, Eslicarbazepine acetate; Drug: Digoxin; Digoxin (days 1 and 2: loading dose of 0.5 mg/day; days 3 to 8: 0.25 mg/day).; Other Names: Lanoxin™
Placebo Comparator: Placebo; Placebo (2 tablets matching BIA 2-093 600 mg tablets) PLC, Placebo Concomitantly with a dose of digoxin (days 1 and 2: loading dose of 0.5 mg/day; days 3 to 8: 0.25 mg/day).	Drug: Placebo; matching placebo; Other Names: PLC, Placebo; Drug: Digoxin; Digoxin (days 1 and 2: loading dose of 0.5 mg/day; days 3 to 8: 0.25 mg/day).; Other Names: Lanoxin™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax - Maximum Steady-state Plasma Concentration	Cmax - Maximum steady-state plasma concentration of BIA 2-005 (BIA 2-093 metabolite) and Digoxin	Day 6 and Day 7: pre-dose; Day 8: pre-dose, ½, 1, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax - Time of Occurrence of Cmax at Steady-state	Time of Occurrence of Cmax Maximum steady-state plasma concentration of BIA 2-005 (BIA 2-093 metabolite) and Digoxin	Day 6 and Day 7: pre-dose; Day 8: pre-dose, ½, 1, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose
AUCτ - Steady-state Area Under the Plasma Concentration-time Profile Over 24 h	Steady-state Area Under the Plasma Concentration-time Profile Over 24 h of BIA 2-005 (BIA 2-093 metabolite) and Digoxin	Day 6 and Day 7: pre-dose; Day 8: pre-dose, ½, 1, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.
• Investigators: Study Director: Manuel Vaz da Silva, MD, PhD, Human Pharmacology Unit / BIAL - Portela & Ca, S.A.

Study record dates

Study Major Dates

• Study Start: May 1, 2002
• Primary Completion (Actual): July 1, 2002
• Study Completion (Actual): July 25, 2002

Study Registration Dates

• First Submitted: June 23, 2014
• First Submitted That Met QC Criteria: June 23, 2014
• First Posted (Estimated): June 24, 2014

Study Record Updates

• Last Update Posted (Actual): April 6, 2025
• Last Update Submitted That Met QC Criteria: March 25, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: BIA 2-093; Eslicarbazepine acetate
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Arrhythmia Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Protective Agents; Cardiotonic Agents; Anticonvulsants; Digoxin; Eslicarbazepine acetate
• Other Study ID Numbers: BIA-2093-107