A Study to Evaluate the Effect of a Single Dose of Digoxin on the Actions in the Bodies of Healthy Subjects After Having Taken Several Doses of YM178

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
ClinicalTrials.gov Identifier:
NCT01663961
First received: July 30, 2012
Last updated: July 1, 2013
Last verified: August 2012
  Purpose

A study that evaluates the interaction in healthy subjects of the heart drug Digoxin on YM178, when the latter is taken on a continuous basis, in order to establish that there is no risk to patients who may take this combination of drugs.


Condition Intervention Phase
Healthy
Drug: YM178 OCAS
Drug: Digoxin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: An Open-label, One-sequence Crossover Study to Evaluate the Effect of Multiple Doses of YM178 on the Pharmacokinetics of Digoxin in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • To determine the effects of steady state YM178 levels on the pharmacokinetics (PK) of a single dose of digoxin [ Time Frame: Pre-dose up to 144 hours post-dose ] [ Designated as safety issue: No ]
    Cmax (Maximum concentration), AUCinf (Area under the plasma concentration - time curve extrapolated until time = infinity)


Secondary Outcome Measures:
  • To evaluate the interaction between YM178 and digoxin in terms of safety and tolerability through assessment of adverse events, ECG and clinical laboratory assessments [ Time Frame: Baseline to Post study visit (Up to 14 days after last dose) ] [ Designated as safety issue: No ]

Enrollment: 25
Study Start Date: September 2008
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: YM178 OCAS + digoxin Drug: YM178 OCAS
oral
Other Names:
  • Mirabegron
  • Myrebtriq
Drug: Digoxin
oral
Other Name: Lanoxin

Detailed Description:

Subjects receive a single oral dose of digoxin on Day 1. A full pharmacokinetic profile of digoxin is obtained for up to 144 hours post-dose. On the morning of Day 7, after the scheduled assessments are done, the subjects leave the clinic and return on Day 9.

From Day 10 up to and including Day 23, subjects receive daily oral doses of YM178 q.d. A single dose of digoxin is given in combination with YM178 on Day 18 (8 days after the first dose of YM178). On this day, a complete pharmacokinetic profile for digoxin is obtained up to 144 hours post-dose.

From Day 16 up to and including Day 19, blood samples for bioanalysis of YM178 are taken regularly. In addition, vital signs, safety ECG (Electrocardiogram) measurements, safety laboratory assessments, adverse events and concomitant medications are monitored throughout the investigational period.

Subjects return for a Post Study Visit 7-14 days after the last dosing occasion.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Female subject must be of non-child bearing potential, i.e. post menopausal, surgically sterilized (e.g. tubal ligation), hysterectomy in medical history, or must practice an adequate (double barrier) non-hormonal contraceptive method to prevent pregnancies
  • Body Mass Index ≥ 18.5 and < 30 kg/m2

Exclusion Criteria:

  • History or presence of cardiac diseases, including arrhythmias (including 1st and 2nd degree atrioventricular heart blocks)
  • History of hypokalemia, hypercalcemia or hypomagnesemia
  • Any of the liver function tests (i.e. ALT, AST and Alkaline phosphatase) above the upper limit of normal at repeated measures
  • Any clinically significant history of asthma, eczema, any other clinically significant allergic condition or previous severe hypersensitivity to any drug (excluding non-active hay fever)
  • Any clinically significant history of gastrointestinal symptoms in the 4 weeks prior to admission to the clinical unit
  • A marked baseline prolongation of QT/QTc interval after repeated measurements of > 450 ms, a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease, or a family history of Long QT Syndrome (LQTS)
  • Regular use of any inducer of liver metabolism (e.g. barbiturates, rifampin) in the 3 months prior to admission to the clinical unit
  • Positive serology test for HBsAg, anti HAV (IgM), anti-HCV or anti-HIV 1+2
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01663961

Locations
France
SGS Aster
Paris, France, 75015
Sponsors and Collaborators
Astellas Pharma Europe B.V.
Investigators
Study Chair: Clinical Study Manager Astellas Pharma Europe B.V.
  More Information

Additional Information:
No publications provided

Responsible Party: Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
ClinicalTrials.gov Identifier: NCT01663961     History of Changes
Other Study ID Numbers: 178-CL-059, 2008-000218-59
Study First Received: July 30, 2012
Last Updated: July 1, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United States: Food and Drug Administration

Keywords provided by Astellas Pharma Inc:
Phase I
Pharmacokinetics
YM178 Oral Controlled Absorption System (OCAS)
Digoxin (Lanoxin)
DDI (Drug-drug interaction)
Open-label
Steady-state
subjects

Additional relevant MeSH terms:
Digoxin
Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Arrhythmia Agents
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014