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

Overactive Bladder Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00856570
• Other study ID #: 178-CL-040
• Secondary ID: EudraCT 2008-000
• Status: Completed
• Phase: Phase 1
• First received: March 4, 2009
• Last updated: July 1, 2013
• Start date: September 2008
• Est. completion date: December 2008

Study information

• Verified date: July 2013
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Overactive Bladder
• Pharmacokinetics
• Urinary Bladder, Overactive

Intervention

Drug:
• warfarin
Oral
• YM178
Oral

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Inc

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	R- and S-warfarin in plasma: AUCinf, AUClast, Cmax, tmax, t1/2, CL/F		Day 1-9 and 15-31	No
Primary	The AUCinf of both enantiomers will be used to assess the potential drug-drug interaction.		Day 1/2 and 15/16	No
Secondary	Adverse events, clinical laboratory tests (hematology, biochemistry, urinalysis), vital signs, 12-lead ECG, physical examination		Day -1 - 31	Yes
Secondary	YM178 in plasma: Ctrough, AUCtau, Cmax, tmax, CL/F		Day 20-24	No
Secondary	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		Day 1-9 and 23-31	No

External Links

•   Link to Results on JAPIC