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

Sponsored by:	Astellas Pharma Inc
Information provided by:	Astellas Pharma Inc
ClinicalTrials.gov Identifier:	NCT00856570

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	Drug: warfarin Drug: YM178	Phase I

Study Type:	Interventional
Study Design:	Basic Science, Non-Randomized, Open Label, Crossover Assignment, Pharmacokinetics/Dynamics Study
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 Warfarin potassium

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 ] [ Designated as safety issue: No ]
The AUCinf of both enantiomers will be used to assess the potential drug-drug interaction. [ Time Frame: Day 1/2 and 15/16 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Adverse events, clinical laboratory tests (hematology, biochemistry, urinalysis), vital signs, 12-lead ECG, physical examination [ Time Frame: Day -1 - 31 ] [ Designated as safety issue: Yes ]
YM178 in plasma: Ctrough, AUCtau, Cmax, tmax, CL/F [ Time Frame: Day 20-24 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]

Enrollment:	24
Study Start Date:	October 2008
Study Completion Date:	January 2009
Primary Completion Date:	January 2009 (Final data collection date for primary outcome measure)

Intervention Details:

Oral

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. 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

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 BV

More Information

No publications provided

Responsible Party:	Astellas Pharma Europe BV ( Disclosure Office Europe )
Study ID Numbers:	178-CL-040, EudraCT 2008-000211-15
Study First Received:	March 4, 2009
Last Updated:	March 4, 2009
ClinicalTrials.gov Identifier:	NCT00856570 History of Changes
Health Authority:	France: Afssaps - French Health Products Safety Agency

Keywords provided by Astellas Pharma Inc:

YM178
Mirabegron
DDI

Phase I
Warfarin
Pharmacokinetics

Study placed in the following topic categories:

Signs and Symptoms
Urinary Bladder, Overactive
Anticoagulants
Cystocele

Urologic Diseases
Urinary Bladder Diseases
Warfarin
Healthy

Additional relevant MeSH terms:

Signs and Symptoms
Urological Manifestations
Urinary Bladder, Overactive
Anticoagulants
Urologic Diseases

Therapeutic Uses
Hematologic Agents
Urinary Bladder Diseases
Warfarin
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 10, 2009