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

• ClinicalTrials.gov Identifier: NCT02172742
• Recruitment Status: Completed
• First Posted: June 24, 2014
• Results First Posted: December 31, 2014
• Last Update Posted: December 31, 2014
• 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 investigate the effects of multiple-dose administration of BIA 2-093 on the steady-state pharmacokinetics of digoxin in healthy subjects.

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

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Effect of BIA 2-093 on the Steady-state Pharmacokinetics of Digoxin in Healthy Volunteers
• Study Start Date: May 2002
• Actual Primary Completion Date: July 2002

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: Lanoxin™

Outcome Measures

Primary Outcome Measures :

1. Cmax - Maximum Steady-state Plasma Concentration [ Time Frame: 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 ]
   Cmax - Maximum steady-state plasma concentration of BIA 2-005 (BIA 2-093 metabolite) and Digoxin

Secondary Outcome Measures :

1. Tmax - Time of Occurrence of Cmax at Steady-state [ Time Frame: 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 ]
   Time of Occurrence of Cmax Maximum steady-state plasma concentration of BIA 2-005 (BIA 2-093 metabolite) and Digoxin
2. AUCτ - Steady-state Area Under the Plasma Concentration-time Profile Over 24 h [ Time Frame: 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 ]
   Steady-state Area Under the Plasma Concentration-time Profile Over 24 h of BIA 2-005 (BIA 2-093 metabolite) and Digoxin

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Portugal

Human Pharmacology Unit (UFH)Section of Clinical Research (SIC), Department of Research & Development (DID), BIAL - Portela & Cª, SA,

Mamede do Coronado, Portugal

Sponsors and Collaborators

Bial - Portela C S.A.

More Information

• Responsible Party: Bial - Portela C S.A.
• ClinicalTrials.gov Identifier: NCT02172742
• Other Study ID Numbers: BIA-2093-107
• First Posted: June 24, 2014
• Results First Posted: December 31, 2014
• Last Update Posted: December 31, 2014
• Last Verified: December 2014

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; Digoxin; Eslicarbazepine acetate; Anti-Arrhythmia Agents; Cardiotonic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators