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

Primary Purpose

Overactive Bladder, Pharmacokinetics

Status

Completed

Phase

Phase 1

Locations

France

Study Type

Interventional

Intervention

warfarin

YM178

About this trial

This is an interventional basic science trial for Overactive Bladder focused on measuring YM178, Mirabegron, DDI, Phase I, Warfarin, Pharmacokinetics

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Outcomes

Primary Outcome Measures

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

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

Secondary Outcome Measures

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

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

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

Full Information

NCT ID

NCT00856570

First Posted

March 4, 2009

Last Updated

July 1, 2013

Sponsor

Astellas Pharma Inc

1. Study Identification

Unique Protocol Identification Number

NCT00856570

Brief Title

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

2. Study Status

Record Verification Date

July 2013

Overall Recruitment Status

Completed

Study Start Date

September 2008 (undefined)

Primary Completion Date

December 2008 (Actual)

Study Completion Date

December 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Astellas Pharma Inc

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Overactive Bladder, Pharmacokinetics

Keywords

YM178, Mirabegron, DDI, Phase I, Warfarin, Pharmacokinetics

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

warfarin

Other Intervention Name(s)

Coumadin

Intervention Description

Oral

Intervention Type

Drug

Intervention Name(s)

YM178

Other Intervention Name(s)

mirabegron

Intervention Description

Oral

Primary Outcome Measure Information:

Title

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

Time Frame

Day 1-9 and 15-31

Title

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

Time Frame

Day 1/2 and 15/16

Secondary Outcome Measure Information:

Title

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

Time Frame

Day -1 - 31

Title

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

Time Frame

Day 20-24

Title

Time Frame

Day 1-9 and 23-31

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Use Central Contact

Organizational Affiliation

Astellas Pharma Europe B.V.

Official's Role

Study Chair

Facility Information:

City

Paris

ZIP/Postal Code

75015

Country

France

12. IPD Sharing Statement

Links:

URL

http://www.clinicaltrials.jp/user/ctrDetail_e.jsp?resultId=669

Description

Link to Results on JAPIC

Learn more about this trial

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

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