Clinical trial NCT00856570: A Clinical Study to Determine the Effect of YM178 on the Pharmacokinetics of Warfarin in Healthy Subjects
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Overactive Bladder
Pharmacokinetics
Keywords: YM178
Mirabegron
DDI
Phase I
Warfarin
Pharmacokinetics
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2009-03-05
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility 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

Primary outcomes:
measure: R- and S-warfarin in plasma: AUCinf, AUClast, Cmax, tmax, t1/2, CL/F
timeFrame: Day 1-9 and 15-31
measure: The AUCinf of both enantiomers will be used to assess the potential drug-drug interaction.
timeFrame: Day 1/2 and 15/16
Secondary outcomes:
measure: Adverse events, clinical laboratory tests (hematology, biochemistry, urinalysis), vital signs, 12-lead ECG, physical examination
timeFrame: Day -1 - 31
measure: YM178 in plasma: Ctrough, AUCtau, Cmax, tmax, CL/F
timeFrame: Day 20-24
measure: 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
timeFrame: Day 1-9 and 23-31
Other outcomes:
Locations:
city: Paris
country: France
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Use Central Contact
role: STUDY_CHAIR
References: