A Clinical Study to Determine the Effect of YM178 on the Pharmacokinetics of Warfarin in Healthy Subjects

Study Description

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Brief Summary:

This study investigates whether YM178 has an effect on the pharmacokinetics of warfarin, to exclude any drug-drug interaction between YM178 and warfarin, and evaluates the safety and tolerability of warfarin alone and combined with YM178.

Condition or disease	Intervention/treatment	Phase
Overactive Bladder; Pharmacokinetics	Drug: warfarin; Drug: YM178	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	24 participants
Allocation:	Non-Randomized
Intervention Model:	Crossover 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 Warfarin in Healthy Subjects
Study Start Date :	September 2008
Actual Primary Completion Date :	December 2008
Actual Study Completion Date :	December 2008

Arms and Interventions

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Intervention Details:

Drug: warfarin
Oral
Other Name: Coumadin
Drug: YM178
Oral
Other Name: mirabegron

Outcome Measures

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Primary Outcome Measures :

1. R- and S-warfarin in plasma: AUCinf, AUClast, Cmax, tmax, t1/2, CL/F [ Time Frame: Day 1-9 and 15-31 ]
2. The AUCinf of both enantiomers will be used to assess the potential drug-drug interaction. [ Time Frame: Day 1/2 and 15/16 ]

Secondary Outcome Measures :

1. Adverse events, clinical laboratory tests (hematology, biochemistry, urinalysis), vital signs, 12-lead ECG, physical examination [ Time Frame: Day -1 - 31 ]
2. YM178 in plasma: Ctrough, AUCtau, Cmax, tmax, CL/F [ Time Frame: Day 20-24 ]
3. Degree of anticoagulation: AUCPT;0-168h (area under the prothrombin time versus time curve from 0 to 168 h after dosing with warfarin), AUCINR;0-168h, maximum PT (PTmax), time to reach PTmax (tPT; max), INRmax, tINR;max [ Time Frame: Day 1-9 and 23-31 ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

• Female who is pregnant
• Any of the liver function tests (i.e. alanine aminotransferase (ALT), aspartate aminotransferase (AST) and Alkaline Phosphatase (AP)) above the upper limit of normal (ULN)
• Any clinically significant history of disease or disorder - gastrointestinal, cardiovascular, respiratory, renal, hepatic, neurological, dermatological, psychiatric or metabolic as judged by the medical investigator
• Abnormal pulse and/or blood pressure measurements and the pre-study as follows: Pulse < 40 or > 90 bpm; mean systolic blood pressure > 140 mmHg; mean diastolic blood pressure > 90 mmHg (blood measurements taken in triplicate after subject has been resting in supine position for 5 min; pulse will be measured automatically
• 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)
• Use of any prescribed or OTC (over-the counter) drugs (including vitamins, natural and herbal remedies, e.g. St. John's wort) in the 2 weeks prior to admission to the Clinical Unit, except for paracetamol (up to 3 g/day)
• Any use of drugs of abuse within 3 months prior to admission to the clinical unit
• History of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to admission to the clinical unit
• History of drinking more than 21 units of alcohol per week (1 unit = 270 ml of beer or 40 ml of spirits or 1 glass of wine) (> 14 units of alcohol for female subjects) within 3 months prior to admission to the clinical unit
• Donation of blood or blood products within 3 months prior to admission to the clinical unit

Contacts and Locations

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Locations

France
Paris, France, 75015

Sponsors and Collaborators

Astellas Pharma Inc

Investigators

Study Chair:	Use Central Contact	Astellas Pharma Europe B.V.

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Link to Results on JAPIC 

Responsible Party:	Astellas Pharma Inc
ClinicalTrials.gov Identifier:	NCT00856570 History of Changes
Other Study ID Numbers:	178-CL-040; EudraCT 2008-000211-15
First Posted:	March 5, 2009
Last Update Posted:	July 2, 2013
Last Verified:	July 2013

Keywords provided by Astellas Pharma Inc:

YM178; Mirabegron; DDI	Phase I; Warfarin; Pharmacokinetics

Additional relevant MeSH terms:

Urinary Bladder, Overactive; Urinary Bladder Diseases; Urologic Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Warfarin; Mirabegron; Anticoagulants	Adrenergic beta-3 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Urological Agents