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

Epilepsy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02172742
• Other study ID #: BIA-2093-107
• Status: Completed
• Phase: Phase 1
• First received: June 23, 2014
• Last updated: December 18, 2014
• Start date: May 2002

Study information

• Verified date: December 2014
• Source: Bial - Portela C S.A.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Portugal: INFARMED, National Authority of Medicines and Health Products, IP
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 13
• Est. primary completion date: July 2002
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Epilepsy

Intervention

Drug:
• BIA 2-093
BIA 2-093 1200 mg once-daily
• Placebo
matching placebo
• Digoxin
Digoxin (days 1 and 2: loading dose of 0.5 mg/day; days 3 to 8: 0.25 mg/day).

Locations

Country	Name	City	State
Portugal	Human Pharmacology Unit (UFH)Section of Clinical Research (SIC), Department of Research & Development (DID), BIAL - Portela & Cª, SA,	Mamede do Coronado

Sponsors (1)

Lead Sponsor	Collaborator
Bial - Portela C S.A.

Country where clinical trial is conducted

Portugal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	AUCt - 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	No