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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01663961
Recruitment Status : Completed
First Posted : August 14, 2012
Last Update Posted : September 1, 2015
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )

Brief Summary:
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 or disease Intervention/treatment Phase
Healthy Drug: YM178 OCAS Drug: Digoxin Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : September 2008
Actual Primary Completion Date : December 2008
Actual Study Completion Date : December 2008

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: YM178 OCAS + digoxin Drug: YM178 OCAS
Other Names:
  • Mirabegron
  • Myrebtriq
Drug: Digoxin
Other Name: Lanoxin

Primary Outcome Measures :
  1. 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 ]
    Cmax (Maximum concentration), AUCinf (Area under the plasma concentration - time curve extrapolated until time = infinity)

Secondary Outcome Measures :
  1. 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) ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01663961

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

Additional Information:
Responsible Party: Astellas Pharma Europe B.V. Identifier: NCT01663961     History of Changes
Other Study ID Numbers: 178-CL-059
2008-000218-59 ( EudraCT Number )
First Posted: August 14, 2012    Key Record Dates
Last Update Posted: September 1, 2015
Last Verified: August 2015

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Europe B.V. ):
Phase I
YM178 Oral Controlled Absorption System (OCAS)
Digoxin (Lanoxin)
DDI (Drug-drug interaction)

Additional relevant MeSH terms:
Anti-Arrhythmia Agents
Cardiotonic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Adrenergic beta-3 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Urological Agents