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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01514812
• Date of registration: 18/01/2012
• Prospective Registration: No
• Primary sponsor: Astellas Pharma Inc
• Public title: A Study to Investigate the Effect of YM150 on the Plasma Concentration of Digoxin in Healthy Subjects
• Scientific title: A Double Blind, Randomized, Two Period Crossover Study To Determine The Effect of Multiple Doses of 120 MG Modified Release Formulation of YM150 on the Steady State Pharmacokinetics of Digoxin in Healthy Subjects
• Date of first enrolment: February 2006
• Target sample size: 24
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01514812
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
• Phase: Phase 1

Countries of recruitment

France

Contacts

• Name: Use Central Contact
• Affiliation: Astellas Pharma Inc

Key inclusion & exclusion criteria

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 ?-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



Age minimum: 18 Years
Age maximum: 55 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Healthy

Pharmacokinetic of Digoxin

Intervention(s)

Drug: placebo

Drug: digoxin

Drug: YM150

Primary Outcome(s)

Cmax of digoxin assessed by its plasma concentration change [Time Frame: for 24 hour after the last dose of each period]

AUC of digoxin assessed by its plasma concentration change [Time Frame: for 24 hour after the last dose of each period]

Secondary Outcome(s)

Safety assessed by the incidence of adverse events, vital signs, 12-lead ECG and labo-tests [Time Frame: for 10 days after dosing]

Changes in the blood coaggregation indexes such as PT(INR), aPTT and FXa [Time Frame: before dosing and 5hr after dosing on days 4 and 8 and 24h and 48h after the last dose]

Secondary ID(s)

150-CL-007

2004-004930-15

Source(s) of Monetary Support

Please refer to primary and secondary sponsors