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

An Open-label, One-sequence Crossover Study to Evaluate the Effect of Multiple Doses of YM178 on the Pharmacokinetics of Digoxin in Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: YM178 OCAS; Drug: Digoxin

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
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • SGS Aster

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: YM178 OCAS + digoxin	Drug: YM178 OCAS; oral; Other Names: Myrebtriq; Mirabegron; Drug: Digoxin; oral; Other Names: Lanoxin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the effects of steady state YM178 levels on the pharmacokinetics (PK) of a single dose of digoxin	Cmax (Maximum concentration), AUCinf (Area under the plasma concentration - time curve extrapolated until time = infinity)	Pre-dose up to 144 hours post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the interaction between YM178 and digoxin in terms of safety and tolerability through assessment of adverse events, ECG and clinical laboratory assessments	Baseline to Post study visit (Up to 14 days after last dose)

Collaborators and Investigators

• Sponsor: Astellas Pharma Europe B.V.

Publications and helpful links

Helpful Links

• Link to Results on JAPIC

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (ACTUAL): December 1, 2008
• Study Completion (ACTUAL): December 1, 2008

Study Registration Dates

• First Submitted: July 30, 2012
• First Submitted That Met QC Criteria: August 13, 2012
• First Posted (ESTIMATE): August 14, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): September 1, 2015
• Last Update Submitted That Met QC Criteria: August 31, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Open-label; Phase I; subjects; Steady-state; YM178 Oral Controlled Absorption System (OCAS); Digoxin (Lanoxin); DDI (Drug-drug interaction)
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Urological Agents; Enzyme Inhibitors; Protective Agents; Adrenergic Agonists; Cardiotonic Agents; Adrenergic beta-Agonists; Adrenergic beta-3 Receptor Agonists; Digoxin; Mirabegron
• Other Study ID Numbers: 178-CL-059; 2008-000218-59 (EUDRACT_NUMBER)