Clinical trial NCT02172742: The Effect of BIA 2-093 on the Steady-state Pharmacokinetics of Digoxin
Official title: The Effect of BIA 2-093 on the Steady-state Pharmacokinetics of Digoxin in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Epilepsy
Keywords: Eslicarbazepine acetate
BIA 2-093
Lead sponsor: Bial - Portela C S.A.
Sponsor class: INDUSTRY
First posted: 2014-06-24
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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).

Eligibility 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.

Primary outcomes:
measure: Cmax - Maximum Steady-state Plasma Concentration
timeFrame: 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 outcomes:
measure: Tmax - Time of Occurrence of Cmax at Steady-state
timeFrame: 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
measure: AUCτ - Steady-state Area Under the Plasma Concentration-time Profile Over 24 h
timeFrame: 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
Other outcomes:
Locations:
city: Trofa
country: Portugal
facility: Human Pharmacology Unit (UFH)Section of Clinical Research (SIC), Department of Research & Development (DID), BIAL - Portela & Cª, SA,
state: Coronado (S.Romão E S. Mamede)
Study officials:
affiliation: Human Pharmacology Unit / BIAL - Portela & Ca, S.A.
name: Manuel Vaz da Silva, MD, PhD
role: STUDY_DIRECTOR
References: