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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00856570
• Date of registration: 04/03/2009
• Prospective Registration: No
• Primary sponsor: Astellas Pharma Inc
• Public title: A Clinical Study to Determine the Effect of YM178 on the Pharmacokinetics of Warfarin in Healthy Subjects
• Scientific 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
• Date of first enrolment: September 2008
• Target sample size: 24
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00856570
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science
• Phase: Phase 1

Countries of recruitment

France

Contacts

• Name: Use Central Contact
• Affiliation: Astellas Pharma Europe B.V.

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 55 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Overactive Bladder

Pharmacokinetics

Intervention(s)

Drug: YM178

Drug: warfarin

Primary Outcome(s)

The AUCinf of both enantiomers will be used to assess the potential drug-drug interaction. [Time Frame: Day 1/2 and 15/16]

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

Secondary Outcome(s)

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]

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]

Secondary ID(s)

178-CL-040

EudraCT 2008-000211-15

Source(s) of Monetary Support

Please refer to primary and secondary sponsors