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

• ClinicalTrials.gov Identifier: NCT00776516
• Recruitment Status: Completed
• First Posted: October 21, 2008
• Last Update Posted: July 3, 2013
• Sponsor: Astellas Pharma Inc
• Information provided by (Responsible Party): Astellas Pharma Inc

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pharmacokinetics of YM178	Drug: mirabegron; Drug: rifampin	Phase 1

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Official Title: 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)
• Study Start Date: October 2008
• Actual Primary Completion Date: December 2008
• Actual Study Completion Date: December 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; mirabegron alone	Drug: mirabegron; oral; Other Name: YM178
Experimental: 2; mirabegron and rifampin	Drug: mirabegron; oral; Other Name: YM178; Drug: rifampin; oral; Other Name: Rifadin

Outcome Measures

Primary Outcome Measures :

1. Assess pharmacokinetics of mirabegron alone and in combination with rifampin [ Time Frame: One month ]

Secondary Outcome Measures :

1. Assess safety and tolerability of mirabegron alone and in combination with rifampin [ Time Frame: one month ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Florida

Miami, Florida, United States, 33126

Sponsors and Collaborators

Astellas Pharma Inc

Investigators

• Study Director: Central Contact; Astellas Pharma Global Development

More Information

Additional Information:

Link to Results on JAPIC 

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 β3-adrenoceptor agonist. Clin Drug Investig. 2013 Jun;33(6):429-40. doi: 10.1007/s40261-013-0084-y.

• Responsible Party: Astellas Pharma Inc
• ClinicalTrials.gov Identifier: NCT00776516
• Other Study ID Numbers: 178-CL-070
• First Posted: October 21, 2008
• Last Update Posted: July 3, 2013
• Last Verified: July 2013

Keywords provided by Astellas Pharma Inc:

Healthy volunteer subjects; CYP3A4 inducer; rifampin; drug interaction; pharmacokinetics; YM178; mirabegron

Additional relevant MeSH terms:

Rifampin; Mirabegron; Antibiotics, Antitubercular; Antitubercular Agents; Anti-Bacterial Agents; Anti-Infective Agents; Leprostatic Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Cytochrome P-450 CYP3A Inducers; Adrenergic beta-3 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Urological Agents