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

NCT00856570 | Completed Phase 1

• 2 other identifiers: 178-CL-040EudraCT 2008-000211-15
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Overactive Bladder; Pharmacokinetics

Keywords

YM178; Mirabegron; DDI; Phase I; Warfarin; Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• R- and S-warfarin in plasma: AUCinf, AUClast, Cmax, tmax, t1/2, CL/F

  Day 1-9 and 15-31

• The AUCinf of both enantiomers will be used to assess the potential drug-drug interaction.

  Day 1/2 and 15/16

Secondary Outcomes (3)

• Adverse events, clinical laboratory tests (hematology, biochemistry, urinalysis), vital signs, 12-lead ECG, physical examination

  Day -1 - 31

• YM178 in plasma: Ctrough, AUCtau, Cmax, tmax, CL/F

  Day 20-24

• 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

Interventions

warfarin DRUG

Oral

Also known as: Coumadin

YM178 DRUG

Oral

Also known as: mirabegron

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Astellas Pharma Inc: lead

Study Sites (1)

Unknown Facility

Paris, 75015, France

Location

MeSH Terms

Conditions

Urinary Bladder, Overactive

Interventions

Warfarin; mirabegron

Condition Hierarchy (Ancestors)

Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Use Central Contact

  Astellas Pharma Europe B.V.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2009
• First Posted: March 5, 2009
• Study Start: September 1, 2008
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: July 2, 2013

Record last verified: 2013-07

Locations

FR (1)