A Study to Evaluate How Mirabegron Enters and Leaves the Bloodstream According to Age and Sex

Healthy Volunteers Clinical Trial

Official title:

An Open-label, Randomized, 2-way Crossover Study to Evaluate the Pharmacokinetics of Mirabegron and Its Metabolites in Healthy Young and Elderly Male and Female Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01285596
• Other study ID #: 178-CL-072
• Secondary ID: 2008-006005-16
• Status: Completed
• Phase: Phase 1
• First received: January 18, 2011
• Last updated: July 1, 2013
• Start date: March 2009
• Est. completion date: November 2009

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)United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Young and elderly, male and female subjects are each given 2 different doses of mirabegron for 7 days each. Levels of mirabegron in the blood are assessed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Healthy elderly subject aged 55 years or more OR Healthy young subject aged 18 to 45 years, inclusive

• Male must agree to sexual abstinence and/or use a highly effective method of birth control from screening until 3 months after last dose of study medication

• Female subject must be of non-child bearing potential, i.e. post menopausal, surgically sterilized (e.g. tubal ligation), hysterectomy in medical history, or must practice an adequate non-hormonal contraceptive method to prevent pregnancies. Non-hormonal contraceptive methods are defined as:

• Sexual abstinence from 1 month before admission until 3 months after discharge, OR

• Subject's sexual partner has been surgically sterilized (since at least 3 months prior to the screening), OR

• Subject is under two (2) of the following contraceptive methods: A) Diaphragm with spermicide; B)Intrauterine device; C)Sexual partner is using condoms in combination with a spermicidal creamDuring the study the subject is willing to use 1 of the 3 following contraceptive methods: diaphragm with spermicide, intrauterine device or partner is using condoms in combination with a spermicidal cream

• Body Mass Index between 18.5 and 30.0 kg/m2, inclusive

Exclusion Criteria:

• Known or suspected hypersensitivity to Mirabegron or any components of the formulation used

• Pregnant or breast feeding within 6 months before screening assessment

• Any of the liver function tests (i.e. ALT, AST and Alkaline phosphatase) above the upper limit of normal at repeated measurements

• Any clinically significant history of asthma, eczema, any other allergic condition or previous severe hypersensitivity to any drug (excluding non-active Hay-fever)

• Any clinically significant history of any other disease or disorder - gastrointestinal, cardiovascular, respiratory, renal, hepatic, neurological, dermatological, psychiatric or metabolic as judged by the investigator

• Any clinically significant abnormality following the investigator's review of the pre-study physical examination, ECG and clinical laboratory tests

• A hemoglobin value <13 g/dl (8.1 mmol/l) for males or <12 g/dl (7.5 mmol/l) for females OR a hematocrit value <40.0% for males or <37% for females OR a Red Blood Cell count <4.5 T/l (4500 mm3) for males or <3.8 T/l (3800 mm3) for females at screening and/or on the day of admission into the clinical unit

• Abnormal pulse and/or blood pressure measurements at the pre-study visit as follows:

Pulse <40 or >90 bpm; mean systolic blood pressure >160 mmHg (elderly) or >140 mmHg (young); mean diastolic blood pressure >100 mmHg (elderly) or >90 mmHg (young), blood pressure 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 occasional use of paracetamol (up to 3 g/day)

• Regular use of any inducer of liver metabolism (e.g. barbiturates, rifampin) in the 3 months prior to admission to the Clinical Unit

• Any use of drugs of abuse within 3 months prior to admission to the Clinical Unit

• History of drinking more than 21 units of alcohol for males or more than 14 units of alcohol per week for females (1 unit = 270 cc of beer or 40 cc of spirits or 1 glass of wine) within 3 months prior to admission to the Clinical Unit

• Positive test for drugs of abuse or positive alcohol test at screening and/or on the day of admission into 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

• Participation in any clinical study within 3 months or participation in more than 3 clinical studies within 12 months, prior to the expected date of enrolment into the study

• Donation of blood or blood products within 3 months prior to admission to the Clinical Unit

• Positive serology test for HBsAg, anti HAV (IgM), anti-HCV or anti-HIV 1+2

• Subjects who, in the opinion of the investigator, are not likely to complete the trial for any reason

• Any clinical condition, which, in the opinion of the investigator would not allow safe completion of the study

Study Design

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

Related Conditions & MeSH terms

• Healthy Volunteers
• Pharmacokinetics of Mirabegron

Intervention

Drug:
• Mirabegron
oral

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Inc

Country where clinical trial is conducted

France, 

References & Publications (1)

Krauwinkel W, van Dijk J, Schaddelee M, Eltink C, Meijer J, Strabach G, van Marle S, Kerbusch V, van Gelderen M. Pharmacokinetic properties of mirabegron, a ß3-adrenoceptor agonist: results from two phase I, randomized, multiple-dose studies in healthy young and elderly men and women. Clin Ther. 2012 Oct;34(10):2144-60. doi: 10.1016/j.clinthera.2012.09.010. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of pharmacokinetics of mirabegron and its metabolites		Days 6 - 14 + Days 21 - 29	No
Secondary	Impedance cardiography assessed through evaluation of cardiac outputs, stroke volume, systemic vascular resistance index, mean arterial blood pressure and heart rate		Days -1, 1, 6 and 7	No

External Links

•   Link to Results on JAPIC