A Clinical Study to Determine the Effect of YM178 on the Pharmacokinetics of Warfarin in Healthy Subjects - Full Text View

Purpose

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	Intervention	Phase
Overactive Bladder Pharmacokinetics	Drug: warfarin Drug: YM178	Phase 1


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Crossover 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 Warfarin in Healthy Subjects

Resource links provided by NLM:

MedlinePlus related topics: Blood Thinners

Drug Information available for: Warfarin Warfarin sodium Mirabegron

U.S. FDA Resources

Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:

R- and S-warfarin in plasma: AUCinf, AUClast, Cmax, tmax, t1/2, CL/F [ Time Frame: Day 1-9 and 15-31 ]
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:

Adverse events, clinical laboratory tests (hematology, biochemistry, urinalysis), vital signs, 12-lead ECG, physical examination [ Time Frame: Day -1 - 31 ]
YM178 in plasma: Ctrough, AUCtau, Cmax, tmax, CL/F [ Time Frame: Day 20-24 ]
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 ]


Enrollment:	24
Study Start Date:	September 2008
Study Completion Date:	December 2008
Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Intervention Details:

Oral

Other Name: Coumadin

Oral

Other Name: mirabegron

Eligibility


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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00856570

Locations


France

Paris, France, 75015

Sponsors and Collaborators

Astellas Pharma Inc

Investigators


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

More Information

Additional Information:

Link to Results on JAPIC This link exits the ClinicalTrials.gov site


Responsible Party:	Astellas Pharma Inc
ClinicalTrials.gov Identifier:	NCT00856570 History of Changes
Other Study ID Numbers:	178-CL-040 EudraCT 2008-000211-15
Study First Received:	March 4, 2009
Last Updated:	July 1, 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 Mirabegron Warfarin 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 Anticoagulants

ClinicalTrials.gov processed this record on June 23, 2017