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

NCT01514812 | Completed Phase 1

• 2 other identifiers: 150-CL-0072004-004930-15
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy; Pharmacokinetic of Digoxin

Keywords

YM150; digoxin; drug-drug interaction; Plasma concentration; darexaban; Pharmacokinetics of digoxin

Outcome Measures

Primary Outcomes (2)

• Cmax of digoxin assessed by its plasma concentration change

  for 24 hour after the last dose of each period

• AUC of digoxin assessed by its plasma concentration change

  for 24 hour after the last dose of each period

Secondary Outcomes (2)

• Changes in the blood coaggregation indexes such as PT(INR), aPTT and FXa

  before dosing and 5hr after dosing on days 4 and 8 and 24h and 48h after the last dose

• Safety assessed by the incidence of adverse events, vital signs, 12-lead ECG and labo-tests

  for 10 days after dosing

Study Arms (2)

YM150-placebo sequence group

EXPERIMENTAL

YM150+digoxin; Washout; Placebo+digoxin

Drug: YM150; Drug: placebo; Drug: digoxin

placebo-YM150 sequence group

EXPERIMENTAL

Placebo+digoxin; Washout; YM150+digoxin

Drug: YM150; Drug: placebo; Drug: digoxin

Interventions

YM150 DRUG

oral - modified release formulation of YM150

Also known as: darexaban

YM150-placebo sequence group; placebo-YM150 sequence group

placebo DRUG

oral

YM150-placebo sequence group; placebo-YM150 sequence group

digoxin DRUG

oral

YM150-placebo sequence group; placebo-YM150 sequence group

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Astellas Pharma Inc: lead

Study Sites (1)

Unknown Facility

Paris, France

Location

Related Publications (1)

• Kadokura T, Groenendaal D, Heeringa M, Mol R, Verheggen F, Garcia-Hernandez A, Onkels H. Darexaban (YM150), an oral direct factor Xa inhibitor, has no effect on the pharmacokinetics of digoxin. Eur J Drug Metab Pharmacokinet. 2014 Mar;39(1):1-9. doi: 10.1007/s13318-013-0141-1. Epub 2013 Jun 11.

  PMID: 23754514 DERIVED

MeSH Terms

Interventions

darexaban; Digoxin

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates

Study Officials

• Use Central Contact

  Astellas Pharma Inc

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2012
• First Posted: January 23, 2012
• Study Start: February 1, 2006
• Primary Completion: April 1, 2006
• Study Completion: April 1, 2006
• Last Updated: January 24, 2012

Record last verified: 2012-01

Locations

FR (1)