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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT00856570
First received: March 4, 2009
Last updated: July 1, 2013
Last verified: July 2013
  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
Endpoint Classification: Pharmacokinetics/Dynamics Study
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:


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: September 2008
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: warfarin
    Oral
    Other Name: Coumadin
    Drug: YM178
    Oral
    Other Name: mirabegron
  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
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:
No publications provided

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
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Urological Agents

ClinicalTrials.gov processed this record on July 31, 2014