Pharmacokinetic Interaction Study to Assess the Effect of Repeat Doses of Rifampin on Mirabegron (YM178) in Healthy Volunteers

A Phase 1, Open-Label, Drug Interaction Study to Evaluate the Effect of Repeat Doses of Rifampin on the Single-Dose Pharmacokinetics of Mirabegron (YM178)

The objective of the study is to assess the PK, safety and tolerability of a single dose of mirabegron alone and in combination with repeat doses of rifampin, a potent CYP3A4 inducer.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics of YM178
• Intervention / Treatment: Drug: mirabegron; Drug: rifampin

Detailed Description

A single group of patients will receive both mirabegron alone and in combination with rifampin

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33126

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Weighs at least 45 kg and body mass index (BMI) between 18 and 32 kg/m2 at Screening
• Normal or not clinically significant 12 lead ECG and clinical laboratory test results at Screening
• Female subjects must be post-menopausal, surgically sterile since at least 1 month prior to screening, or practicing effective non-hormonal contraceptive methods. All females must be non-lactating, and should have a negative result for the pregnancy test at Screening and on Day -1
• Negative drug and alcohol screens

Exclusion Criteria:

• Has known or suspected hypersensitivity to mirabegron or rifampin
• Liver enzyme test abnormalities (ALT, AST, or bilirubin) above the upper limit of normal
• History or presence of psychiatric illness, serious active or recurrent infection or hepatitis
• Previous history of cancer other than basal cell carcinoma or Stage 1 squamous cell carcinoma that has not been in remission for at least 5 years prior to the dose of study drug
• Donation or loss of ≥ 450 mL blood within 56 days prior to study drug administration or has donated plasma within 7 days prior to study drug administration
• Received or is anticipated to receive a prescription drug within 14 days prior to Day -1 or within 30 days prior to Day -1 for any long acting treatments. Use of any over-the-counter medications, including complementary and alternative medicines (except for occasional use of acetaminophen of up to 2000 mg/day but not more than 4 days per week) within 14 days prior to Day -1
• History of substance abuse within 6 months prior to Screening
• Current participation in another clinical trial or is taking or has been taking an investigational drug in the 30 days or 10 half lives of the drug, whichever is longer, prior to dosing
• Known to have hepatitis or HIV-1 and/or HIV-2 or is positive for hepatitis A antibody IgM, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody at Screening
• Subject has consumed alcohol, caffeine-containing food or beverages, grapefruit juice, grapefruit-containing products or Seville oranges within 48 prior to Day -1

Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; mirabegron alone	Drug: mirabegron; oral; Other Names: YM178
Experimental: 2; mirabegron and rifampin	Drug: mirabegron; oral; Other Names: YM178; Drug: rifampin; oral; Other Names: Rifadin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Assess pharmacokinetics of mirabegron alone and in combination with rifampin	One month

Secondary Outcome Measures

Outcome Measure	Time Frame
Assess safety and tolerability of mirabegron alone and in combination with rifampin	one month

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Investigators: Study Director: Central Contact, Astellas Pharma Global Development

Publications and helpful links

General Publications

• Lee J, Moy S, Meijer J, Krauwinkel W, Sawamoto T, Kerbusch V, Kowalski D, Roy M, Marion A, Takusagawa S, van Gelderen M, Keirns J. Role of cytochrome p450 isoenzymes 3A and 2D6 in the in vivo metabolism of mirabegron, a beta3-adrenoceptor agonist. Clin Drug Investig. 2013 Jun;33(6):429-40. doi: 10.1007/s40261-013-0084-y.

Helpful Links

• Link to Results on JAPIC

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: October 20, 2008
• First Submitted That Met QC Criteria: October 20, 2008
• First Posted (Estimate): October 21, 2008

Study Record Updates

• Last Update Posted (Estimate): July 3, 2013
• Last Update Submitted That Met QC Criteria: July 1, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: pharmacokinetics; drug interaction; YM178; mirabegron; rifampin; CYP3A4 inducer; Healthy volunteer subjects
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Urological Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Adrenergic Agonists; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Adrenergic beta-Agonists; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Adrenergic beta-3 Receptor Agonists; Rifampin; Mirabegron
• Other Study ID Numbers: 178-CL-070