The Effect of BIA 2-093 on the Steady-state Pharmacokinetics of Digoxin
- Registration Number
- NCT02172742
- Lead Sponsor
- Bial - Portela C S.A.
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 13
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Placebo 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). BIA 2-093 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). Placebo Digoxin 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). BIA 2-093 Digoxin 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).
- Primary Outcome Measures
Name Time Method Cmax - Maximum Steady-state Plasma Concentration 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
Name Time Method Tmax - Time of Occurrence of Cmax at Steady-state 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
AUCτ - Steady-state Area Under the Plasma Concentration-time Profile Over 24 h 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
Trial Locations
- Locations (1)
Human Pharmacology Unit (UFH)Section of Clinical Research (SIC), Department of Research & Development (DID), BIAL - Portela & Cª, SA,
🇵🇹Trofa, Coronado (S.Romão E S. Mamede), Portugal