Post-marketing Study to Evaluate the Effect of Mirabegron on the Plasma Concentration of Tolterodine

Post-Marketing Study of Mirabegron - A Pharmacokinetic Study to Assess Drug-Drug Interaction Between Mirabegron and Tolterodine -

To assess the effect of multiple doses of mirabegron to postmenopausal adult female subjects on the pharmacokinetics (PK) of tolterodine and its metabolites.

In addition, the safety of these products will be assessed.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Kanto, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Subjects of two years after menopause
• Body weight (at screening) ≥ 40.0 kg and < 70.0 kg
• Body mass index (BMI) (at screening) ≥ 17.6 kg/m2 and < 26.4 kg/m2
• Healthy, as judged by the investigator/sub-investigator based on medical history and the results of physical examination (subjective symptoms and objective findings) and all tests obtained at screening and during the period from hospital admission (at single dosing phase) to immediately before study medication.

Exclusion Criteria:

• Received or scheduled to receive any investigational drugs in other clinical trials, post-marketing studies, or clinical studies within 120 days before the screening or during the period from the screening to hospitalization (Day -2).
• Donated or scheduled to donate 400 mL of whole blood within 90 days before the screening or during the period from the screening to hospitalization (Day -2), 200 mL of whole blood within 30 days before the screening or during the period from the screening to hospitalization (Day -2), or blood components within 14 days before the screening or during the period from the screening to hospitalization (Day -2).
• Any deviation of the laboratory tests at screening or hospitalization (Day -2).
• A deviation from the normal range of blood pressure, pulse rae, or body temperature at screening or hospitalization (Day -2) Supine blood pressure: Systolic blood pressure: ≥90 mmHg, ≤140 mmHg, Diastolic blood pressure: ≥40 mmHg, ≤90 mmHg Supine pulse rate; ≥40 bpm, ≤99 bpm Axillary body temperature; ≥35.0°C, ≤37.0°C
• History of drug allergies
• Upper gastrointestinal disease (e.g., nausea, vomiting, and stomachache) within 7 days before hospitalization (Day -2)
• Concurrent or previous hepatic disease (e.g., viral hepatitis, drug-induced liver injury, and hepatic impairment)
• Concurrent or previous heart disease (e.g., congestive heart failure, angina pectoris, and arrhythmia requiring treatment)
• Concurrent or previous GI disease (e.g., ileus paralytic, gastric atony, intestinal atony, colitis ulcerative, peptic ulcer and gastroesophageal reflux esophagitis; except for a history of appendicitis).
• Concurrent or previous renal disease (e.g., acute renal failure, glomerulonephritis, and interstitial nephritis)
• Concurrent or previous endocrine disease (e.g., hyperthyroidism and blood growth hormone abnormal)
• Concurrent or previous cerebrovascular disorder (e.g., cerebral infarction)
• Previous use of mirabegron or tolterodine
• Excessive smoking or drinking habit

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: treatment group	Drug: mirabegron; Oral; Other Names: YM178; Betanis® tablets; Drug: tolterodine; Oral; Other Names: Detrusitol® Capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma concentration of unchanged mirabegron	Day 14
Plasma concentration of unchanged tolterodine	Day 7, Day 14

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma concentration of tolterodine metabolites (5-hydroxymethyl tolterodine; 5-HMT)	Day 7, Day 14
Safety assessed by the incidence of adverse events, vital signs, clinical labo-tests, and 12-lead ECG	Day -2, Day 8, Day 15, Day 22

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: October 15, 2013
• First Submitted That Met QC Criteria: October 15, 2013
• First Posted (Estimate): October 17, 2013

Study Record Updates

• Last Update Posted (Estimate): October 17, 2013
• Last Update Submitted That Met QC Criteria: October 15, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: Open-label design; Pharmacokinetics; Mirabegron; Drug-Drug Interaction
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Adrenergic Agonists; Adrenergic beta-Agonists; Adrenergic beta-3 Receptor Agonists; Mirabegron; Tolterodine Tartrate
• Other Study ID Numbers: 178-CL-111