Pharmacokinetics of Oral Mirabegron With Different Release Rates Versus Intravenous (IV) Mirabegron

A Phase 1, Open-Label, Randomized, Parallel Dose Group Study to Assess the Pharmacokinetics of Mirabegron OCAS Formulations With Different Release Rates Versus IV Infusion in Healthy Volunteers

The purpose of this study is to assess the pharmacokinetics of three doses of oral mirabegron formulations with three different release rates versus three doses of mirabegron administered intravenously; to study safety and side effects of the oral and IV doses of mirabegron.

Study Overview

• Status: Completed
• Conditions: Healthy; Pharmacokinetics of Mirabegron
• Intervention / Treatment: Drug: mirabegron; Drug: mirabegron

Detailed Description

Subjects will be randomly assigned to one of three oral mirabegron doses and then randomly assigned to one of three oral mirabegron doses and then randomly assigned to one of six treatment sequences.

For all subjects the first treatment will be a reference IV dose. Treatments 2, 3, and 4 will be a random order of slow, fast and target release oral doses of mirabegron. Treatment 5 will be a target release dose of mirabegron from a different batch.

There will be at least 10 day washout between dose administrations.

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Tacoma, Washington, United States, 98418

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:

• The subject must weigh at least 45 kg and have a body mass index (BMI) between 20.0 and 32.0 kg/m2
• The subject must have a normal or clinically nonsignificant 12 lead ECG as well as normal or clinically non-significant laboratory test results
• Female subjects must be post-menopausal (defined as at least 2 years without menses) surgically sterile, or practicing effective contraception, and will continue to use effective contraception during the study period. All females must be non-lactating, and should have a negative pregnancy test result
• The subject must have negative test results for drugs of abuse and alcohol screens
• The subject must have a good venous access in both arms

Exclusion Criteria:

• The subject has evidence of QTc interval >430 msec for male, >450 msec for female
• The subject has liver function test values (ALT, AST, or bilirubin) above the upper limit of normal
• The subject has a history or presence of psychiatric illness, serious active or recurrent infection
• The subject has a 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
• The subject has donated or lost ≥ 450 mL blood within 56 days prior to study drug administration or has donated plasma within 7 days prior to study drug administration
• The subject has received or is anticipated to receive a prescription drug within 14 days (within 30 days for any long acting treatments such as depot formulations). Subject has taken any over-the-counter (OTC) medications, including complementary and alternative medicines (except for oral contraceptives and occasional use of acetaminophen of up to 2000 mg/day but not more than 4 days per week) within 14 days
• The subject has consumed alcohol, xanthine derivative-containing beverages/food (tea/chocolate), grapefruit juice, grapefruit-containing products or Seville oranges (e.g., bitter marmalade) within 48 hours before admission into the unit
• The subject has used tobacco-containing products and nicotine-containing products within 6 months
• The subject consumes more than 5 units of alcoholic beverages (one unit is 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits) per week, or has a history of substance abuse, drug addiction, or alcoholism within past 2 years
• The subject is 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1. mirabegron, low dose; Oral mirabegron 25 mg	Drug: mirabegron; oral tablet; Other Names: YM178; Drug: mirabegron; IV solution; Other Names: YM178
Experimental: 2. mirabegron, middle dose; Oral mirabegron 50 mg	Drug: mirabegron; oral tablet; Other Names: YM178; Drug: mirabegron; IV solution; Other Names: YM178
Experimental: 3. mirabegron, higher dose; Oral mirabegron 100 mg	Drug: mirabegron; oral tablet; Other Names: YM178; Drug: mirabegron; IV solution; Other Names: YM178

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Characterize the pharmacokinetic profile of 3 doses of oral mirabegron formulations with three different release rates vs. three doses of mirabegron administered intravenously	2 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Assess the safety and tolerability of three doses of orally administered mirabegron formulated with three different release rates	2 months
Assess the safety and tolerability of intravenously administered mirabegron	2 months

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc

Publications and helpful links

General Publications

• Eltink C, Lee J, Schaddelee M, Zhang W, Kerbusch V, Meijer J, van Marle S, Grunenberg N, Kowalski D, Drogendijk T, Moy S, Iitsuka H, van Gelderen M, Matsushima H, Sawamoto T. Single dose pharmacokinetics and absolute bioavailability of mirabegron, a beta(3)-adrenoceptor agonist for treatment of overactive bladder. Int J Clin Pharmacol Ther. 2012 Nov;50(11):838-50. doi: 10.5414/CP201782.

Helpful Links

• Link to Results on JAPIC

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2009
• Primary Completion (Actual): July 13, 2009
• Study Completion (Actual): July 13, 2009

Study Registration Dates

• First Submitted: July 13, 2009
• First Submitted That Met QC Criteria: July 14, 2009
• First Posted (Estimate): July 15, 2009

Study Record Updates

• Last Update Posted (Actual): October 18, 2018
• Last Update Submitted That Met QC Criteria: October 16, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: pharmacokinetics; YM178; mirabegron; oral administration; IV infusion; Healthy volunteer subjects
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Urological Agents; Adrenergic Agonists; Adrenergic beta-Agonists; Adrenergic beta-3 Receptor Agonists; Mirabegron
• Other Study ID Numbers: 178-CL-076

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."