A Study to Investigate the Effect of YM150 on the Plasma Concentration of Digoxin in Healthy Subjects

Astellas

Status and phase

Completed

Phase 1

Conditions

Healthy

Pharmacokinetic of Digoxin

Treatments

Drug: placebo

Drug: YM150

Drug: digoxin

Study type

Interventional

Funder types

Industry

Identifiers

NCT01514812

2004-004930-15 (EudraCT Number)

150-CL-007

Details and patient eligibility

About

This study is to evaluate the effect of YM150 on the plasma concentration of digoxin in healthy subjects.

Full description

The study will be of a double blind, randomized, two period crossover design. Two treatments, digoxin in combination with YM150, and digoxin in combination with placebo, will be evaluated. Each subject will receive both treatments in random order. Placebo will be used to maintain the blind. Males and females will be equally divided over the treatment orders.

Subjects will be dosed with digoxin and either YM150 or placebo for 8 days to reach steady state. In the second period the subjects will receive digoxin and the alternate treatment. There will be a washout period of at least 10 days between the consecutive treatments. In both study periods the subjects will be admitted the day prior to study drug administration (Day 0). The subjects will be discharged on Day 10. Approximately one week after the last discharge, the subjects will return to the unit for a post study visit.

Enrollment

24 patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Healthy, as judged by the investigator or sub-investigator based on the results of physical examinations and all tests
Body weight: male: ≥60 kg, <100 kg; female: ≥45.0 kg, <80.0 kg
BMI (at screening): ≥18.0, <30.0

Exclusion criteria

Female subjects of child-bearing potential, not practicing adequate methods to prevent pregnancies, like abstinence or double barrier methods
Known or suspected hypersensitivity / allergy to FXa inhibitors, digoxin, or heart glycosides in general or the constituents of the formulations used
History of and/or any sign or symptom indicating current abnormal hemostasis or blood dyscrasia, including but not limited to neutropenia, thrombocytopenia, thrombocytopathy, thromboasthenia, hemophilia, Von Willebrand's disease, and vascular purpura, bleeding gums, or frequent nose bleeding
Family history of congenital vascular malformation (e.g. Marfan's Syndrome) and/or bleeding disorder (e.g. hemophilia, Von Willebrand's disease, Christmas disease)
PT or aPTT at the screening visit outside the normal range
History of peptic ulcer or of any other organic lesion susceptible to bleed
Any surgical intervention (including tooth extraction) or trauma within the last 3 months preceding the initiation of the study
Any clinically significant history of upper gastrointestinal symptoms (such as nausea, vomiting, abdominal discomfort or upset, or heartburn) in the 4 weeks prior to admission to the Research Unit
Any clinically significant history of any other disease or disorder - gastrointestinal, cardiovascular, respiratory, renal, hepatic, neurological, dermatological, psychiatric or metabolic
Any of the liver function tests (ALAT, ASAT, LDH and γ-GT) above the upper limit of normal range (ULN)
Any clinically significant abnormality following the investigator's review of the prestudy physical examination, ECG and clinical laboratory tests
Abnormal pulse rate and blood pressure measurements at the pre-study visit as follows: Pulse rate <40 or >90 bpm; systolic blood pressure <95 or >160 mmHg; diastolic blood pressure <40 or >95 mmHg (measurements taken after subject has been resting in supine position for 5 min)
Regular use of any prescribed or OTC (over-the-counter) drugs (including natural and herbal remedies and especially those with P-gp inhibiting activity, like St. John's worth) in the four weeks prior to admission to the Research Unit OR any use of such drugs (including natural and herbal remedies) as well as vitamins in the two weeks prior to admission to the Research Unit
Donation of blood or blood products within 3 months prior to admission to the Research Unit