A Study to Investigate the Effect of Food With Mirabegron in Healthy Chinese Participants

• Sponsor: Astellas Pharma China, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04501640
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 4
• Actual Duration (Months): 1.2
• Patients Per Site Per Month: 20.3

Study Details

Study Description

Brief Summary

This study determined the effect of food on the pharmacokinetics (PK) of single oral doses of mirabegron in healthy Chinese male and female participants.

This study also evaluated the safety and tolerability of single oral doses of mirabegron in healthy Chinese male and female participants.

Condition or Disease	Intervention/Treatment	Phase
Pharmacokinetics of Mirabegron; Food Effect; Healthy Chinese Subjects	Drug: mirabegron	Phase 4

Detailed Description

An open-label, randomized, 2-period, single oral dose crossover design at 2 dose levels in healthy Chinese male and female participants. Each participant took part in 2 periods separated by a washout of at least 10 days between investigational product (IP) administrations in each period.

Participants were screened for up to 21 days prior to IP administration on day 1 of period 1. Eligible participants were admitted to the clinical unit on day -1 of each period and were confined until the last pharmacokinetic sample had been drawn within each period. PK samples were collected predose on day 1 of each period and at multiple time points following each dose.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: This was a two-way crossover design with 2 period and 2 dose groups. Participants were randomized to 1 of 4 sequences dependent on dose and period assigned.This was a two-way crossover design with 2 period and 2 dose groups. Participants were randomized to 1 of 4 sequences dependent on dose and period assigned.
• Masking: None (Open Label)
• Masking Description: This was an open label study.
• Primary Purpose: Basic Science
• Official Title: A Phase 4 Open-label, Randomized, Single Oral Dose, Two-way Crossover Study to Investigate the Effect of Food on the Pharmacokinetics of Mirabegron in Healthy Chinese Subjects
• Actual Study Start Date: Sep 21, 2020
• Actual Primary Completion Date: Oct 14, 2020
• Actual Study Completion Date: Oct 27, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mirabegron 25 mg fed/Mirabegron 25 mg fasted Participants received single dose of 25 mg mirabegron tablet under fed condition orally, on day 1 of period 1 followed by single dose of 25 milligram (mg) mirabegron tablet under fasted condition orally, on day 1 of period 2. A washout period of 10 days was maintained between the mirabegron administrations in each period.	Drug: mirabegron; Oral adminstration; Other Names: Betmiga
Experimental: Mirabegron 25 mg fasted/Mirabegron 25 mg fed Participants received single dose of 25 mg mirabegron tablet under fasted condition orally, on day 1 of period 1 followed by single dose of 25 mg mirabegron tablet under fed condition orally, on day 1 of period 2. A washout period of 10 days was maintained between the mirabegron administrations in each period.	Drug: mirabegron; Oral adminstration; Other Names: Betmiga
Experimental: Mirabegron 50 mg fed/Mirabegron 50 mg fasted Participants received single dose of 50 mg mirabegron tablet under fed condition orally, on day 1 of period 1 followed by single dose of 50 mg mirabegron tablet under fasted condition orally, on day 1 of period 2. A washout period of 10 days was maintained between the mirabegron administrations in each period.	Drug: mirabegron; Oral adminstration; Other Names: Betmiga
Experimental: Mirabegron 50 mg fasted/Mirabegron 50 mg fed Participants received single dose of 50 mg mirabegron under fasted condition orally, on day 1 of period 1 followed by single dose of 50 mg mirabegron tablet under fed condition orally, on day 1 of period 2. A washout period of 10 days was maintained between the mirabegron administrations in each period.	Drug: mirabegron; Oral adminstration; Other Names: Betmiga

Outcome Measures

Primary Outcome Measures

1. Area Under The Concentration-Time Curve (AUC) From The Time of Dosing Extrapolated to Time Infinity (AUCinf) For Mirabegron [Day 1: predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 72 and 96 hour(s) postdose of each period]

   AUCinf for mirabegron was reported for the plasma samples collected.

2. Area Under The Concentration-Time Curve (AUC) From The Time of Dosing to The Last Measurable Concentration (AUClast) For Mirabegron [Day 1: predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 72 and 96 hour(s) postdose of each period]

   AUClast for mirabegron was reported for the plasma samples collected.

3. Maximum Concentration (Cmax) For Mirabegron [Day 1: predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 72 and 96 hour(s) postdose of each period]

   Cmax for mirabegron was reported from the plasma samples collected.

Secondary Outcome Measures

1. Number of Participants With Adverse Events (AE) [From date of informed consent signed to end of study (up to 24 days)]

   An AE is any untoward medical occurrence in a participant administered an study drug, and which does not necessarily have to have a causal relationship with this study drug. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug whether or not considered related to the study drug. An AE is considered "serious" if, in the view of either the investigator or sponsor, the event results in death, is life-threatening, results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions results in congenital anomaly, or birth defect, requires inpatient hospitalization, other medically important AE. An AE with onset at any time from first dosing until last scheduled procedure was classified as a TEAE.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Subject has a body mass index range of 19.0 to 24.9 kg/m^2, inclusive and weighs at least 50 kg for male subjects and 45 kg for female subjects at screening.

• Female subject is not pregnant and at least 1 of the following conditions apply:

• Not a woman of childbearing potential (WOCBP)

• WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 30 days after final IP administration

• Female subject must agree not to breastfeed starting at screening and throughout the study period and for 30 days after final IP administration.

• Female subject must not donate ova starting at first dose of IP and throughout the study period and for 30 days after final IP administration.

• Male subject with female partner(s) of childbearing potential (including breastfeeding partner[s]) must agree to use contraception throughout the study period and for 30 days after final IP administration.

• Male subject must not donate sperm during the study period and for 30 days after final IP administration.

• Male subject with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 30 days after final IP administration.

• Subject agrees not to participate in another interventional study while participating in the present study, defined as 84 days prior screening until completion of the last study visit.

Exclusion Criteria:

• Female subject who has been pregnant within 6 months prior to screening or breastfeeding within 3 months prior to screening.

• Subject has a known or suspected hypersensitivity to mirabegron or any components of the formulation used.

• Subject has had previous exposure with mirabegron.

• Subject has any of the liver function tests (alkaline phosphatase, alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyl transferase and total bilirubin [TBL]) ≥ 1.5 × upper limit of normal (ULN) on day -1 of period 1.

• Subject has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies) prior to first IP administration.

• Subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal and/or other major disease or malignancy.

• Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within 1 week prior to day -1 of period 1.

• Subject has any of the following concerns with regard to tuberculosis:

• History of active tuberculosis

• Abnormalities detected in a chest X-ray on day -1 of period 1

• Contact with infectious tuberculous patients

• Subject has any clinically significant abnormality following the physical examination, electrocardiogram (ECG) and protocol-defined clinical laboratory tests at screening or on day -1 of period 1.

• Participant has a mean pulse < 45 bpm, > 99 bpm; mean body temperature < 35.0°C, > 37.5°C; mean systolic blood pressure < 90 mmHg, ≥ 140 mmHg; mean diastolic blood pressure < 40 mmHg, ≥ 90 mmHg (measurements taken in triplicate after participant has been resting in the supine position for at least 5 minutes) at screening or on day-1 of period 1. If the mean blood pressure exceeds the limits above, 1 additional triplicate may be taken.

• Participant has a mean corrected QT interval using Fridericia's formula (QTcF) of: ≥ 430 msec (for male subjects) ≥ 450 msec (for female subjects) at screening or on day-1 of period 1. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG may be taken.

• Subject has used any prescribed or nonprescribed drugs (including vitamins, natural and herbal remedies, e.g., St. John's Wort and traditional Chinese medicine) in the 2 weeks prior to first IP administration, except for occasional use of paracetamol (up to 2 g/day), topical dermatological products, including corticosteroid products, hormonal contraceptives or hormone replacement therapy (HRT).

• Subject has a history of smoking > 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to day -1 of period 1.

• Subject has a history of consuming > 21 units for male subjects or > 14 units for female subjects of alcohol per week within 3 months prior to day -1 of period 1 (note: 1 unit = 10 g pure alcohol, 250 mL of beer [5%], 35 mL of spirits [35%] or 100 mL of wine [12%]) or the subject has a history of alcohol-dependency, drug-dependency, chemical-dependency, or alcohol or drug abuse within 2 years prior to screening or the subject tests positive for alcohol at screening or on day -1 of period 1.

• Subject has used any drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and/or opiates) within 3 months prior to day -1 of period 1 or the subject tests positive for drugs of abuse (amphetamines, benzodiazepines, cannabinoids, cocaine and opiates) at screening or on day -1 of period 1.

• Subject has used any inducer of metabolism (e.g., barbiturates and rifampin) in the 3 months prior to day -1 of period 1.

• Subject has had significant blood loss, donated ≥ 400 mL of whole blood within 90 days, ≥ 200 mL of whole blood within 30 days or donated blood components within 14 days prior to day -1 of period 1 and/or received a transfusion of any blood or blood products within 60 days.

• Subject has a positive serology test for hepatitis A virus antibodies (immunoglobulin M), hepatitis B core antibodies, hepatitis B surface antigen, hepatitis C virus antibodies, human immunodeficiency virus or syphilis at screening.

• Subject is an employee of Astellas, the study-related contract research organizations or the clinical unit.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site CN86001	Shanghai		China

Sponsors and Collaborators

• Astellas Pharma China, Inc.

Investigators

• Study Director: Executive Director, Astellas Pharma China, Inc.

Study Documents (Full-Text)

• Study Protocol - Sep 17, 2020
• Statistical Analysis Plan - Jun 16, 2020

More Information

Additional Information:

• Link to results and other applicable study documents on the Astellas Clinical Trials website
• Link to plain language summary of the study on the Trial Results Summaries website

Publications

None provided.

• Responsible Party: Astellas Pharma China, Inc.
• ClinicalTrials.gov Identifier: NCT04501640
• Other Study ID Numbers: 178-MA-2294; CTR20201670
• First Posted: Aug 6, 2020
• Last Update Posted: Nov 12, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Astellas Pharma China, Inc.: mirabegron; pharmacokinetics; two-way crossover
• Additional relevant MeSH terms: Mirabegron

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at one site in China.
Pre-assignment Detail	Healthy Chinese female and male participants between 18 to 45 years of age, inclusive (at screening), and met all of the inclusion and none of the exclusion criteria were eligible to participate in this study.

Arm/Group Title	Mirabegron 25 mg Fed/Mirabegron 25 mg Fasted	Mirabegron 25 mg Fasted/Mirabegron 25 mg Fed	Mirabegron 50 mg Fed/Mirabegron 50 mg Fasted	Mirabegron 50 mg Fasted/Mirabegron 50 mg Fed
Arm/Group Description	Participants received single dose of 25 milligrams (mg) mirabegron tablet under fed condition orally, on day 1 of period 1 followed by single dose of 25 mg mirabegron tablet under fasted condition orally, on day 1 of period 2. A washout period of 10 days was maintained between the mirabegron administrations in each period.	Participants received single dose of 25 mg mirabegron tablet under fasted condition orally, on day 1 of period 1 followed by single dose of 25 mg mirabegron tablet under fed condition orally, on day 1 of period 2. A washout period of 10 days was maintained between the mirabegron administrations in each period.	Participants received single dose of 50 mg mirabegron tablet under fed condition orally, on day 1 of period 1 followed by single dose of 50 mg mirabegron tablet under fasted condition orally, on day 1 of period 2. A washout period of 10 days was maintained between the mirabegron administrations in each period.	Participants received single dose of 50 mg mirabegron tablet under fasted condition orally, on day 1 of period 1 followed by single dose of 50 mg mirabegron tablet under fed condition orally, on day 1 of period 2. A washout period of 10 days was maintained between the mirabegron administrations in each period.
Period Title: Period 1 (5 Days)
STARTED	6	6	6	6
COMPLETED	6	6	6	6
NOT COMPLETED	0	0	0	0
Period Title: Period 1 (5 Days)
STARTED	6	6	6	6
COMPLETED	6	6	6	6
NOT COMPLETED	0	0	0	0
Period Title: Period 1 (5 Days)
STARTED	6	6	6	6
COMPLETED	6	6	6	6
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Mirabegron 25 mg Fed/Mirabegron 25 mg Fasted	Mirabegron 25 mg Fasted/Mirabegron 25 mg Fed	Mirabegron 50 mg Fed/Mirabegron 50 mg Fasted	Mirabegron 50 mg Fasted/Mirabegron 50 mg Fed	Total
Arm/Group Description	Participants received single dose of 25 mg mirabegron tablet under fed condition orally, on day 1 of period 1 followed by single dose of 25 mg mirabegron tablet under fasted condition orally, on day 1 of period 2. A washout period of 10 days was maintained between the mirabegron administrations in each period.	Participants received single dose of 25 mg mirabegron tablet under fasted condition orally, on day 1 of period 1 followed by single dose of 25 mg mirabegron tablet under fed condition orally, on day 1 of period 2. A washout period of 10 days was maintained between the mirabegron administrations in each period.	Participants received single dose of 50 mg mirabegron tablet under fed condition orally, on day 1 of period 1 followed by single dose of 50 mg mirabegron tablet under fasted condition orally, on day 1 of period 2. A washout period of 10 days was maintained between the mirabegron administrations in each period.	Participants received single dose of 50 mg mirabegron tablet under fasted condition orally, on day 1 of period 1 followed by single dose of 50 mg mirabegron tablet under fed condition orally, on day 1 of period 2. A washout period of 10 days was maintained between the mirabegron administrations in each period.	Total of all reporting groups
Overall Participants	6	6	6	6	24
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	27.8 (7.8)	25.0 (4.8)	26.7 (7.2)	24.5 (3.7)	26.0 (5.8)
Sex: Female, Male (Count of Participants)
Female	1 16.7%	1 16.7%	1 16.7%	1 16.7%	4 16.7%
Male	5 83.3%	5 83.3%	5 83.3%	5 83.3%	20 83.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	6 100%	6 100%	6 100%	6 100%	24 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	6 100%	6 100%	6 100%	6 100%	24 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Area Under The Concentration-Time Curve (AUC) From The Time of Dosing Extrapolated to Time Infinity (AUCinf) For Mirabegron
Description	AUCinf for mirabegron was reported for the plasma samples collected.
Time Frame	Day 1: predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 72 and 96 hour(s) postdose of each period

Outcome Measure Data

Analysis Population Description

The pharmacokinetic analysis set (PKAS) consisted of all participants who received at least 1 dose of investigational product (IP) for which concentration data were available to facilitate derivation of at least 1 primary pharmacokinetic parameter.

Arm/Group Title	Mirabegron 25 mg Fed	Mirabegron 25 mg Fasted	Mirabegron 50 mg Fed	Mirabegron 50 mg Fasted
Arm/Group Description	Participants received single dose of 25 mg mirabegron tablet under fed condition orally, on day 1 of either period 1 or period 2.	Participants received single dose of 25 mg mirabegron tablet under fasted condition orally, on day 1 of either period 1 or period 2.	Participants received single dose of 50 mg mirabegron tablet under fed condition orally, on day 1 of either period 1 or period 2.	Participants received single dose of 50 mg mirabegron tablet under fasted condition orally, on day 1 of either period 1 or period 2.
Measure Participants	12	12	12	12
Geometric Mean (Geometric Coefficient of Variation) [Hour*nanogram per milliliter (h*ng/mL)]	81.8 (37.2)	143 (39.3)	263 (26.9)	429 (36.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 25 mg Fed, Mirabegron 25 mg Fasted
	Comments	Assessment based on an analysis of variance (ANOVA) performed on natural log-transformed parameters with food condition and period as a fixed effects and participant as a random effect.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geomteric Least Squares (LS) Mean Ratio
	Estimated Value	57.06
	Confidence Interval	(2-Sided) 90%; 46.21 to 70.47
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ratios and confidence intervals are transformed back to raw scale & values are expressed as percentages.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg Fed, Mirabegron 50 mg Fasted
	Comments	Assessment based on an ANOVA performed on natural log-transformed parameters with food condition and period as a fixed effects and participant as a random effect.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric LSMean Ratio
	Estimated Value	61.42
	Confidence Interval	(2-Sided) 90%; 52.06 to 72.47
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ratios and confidence intervals are transformed back to raw scale & values are expressed as percentages.

2. Primary Outcome

Title	Area Under The Concentration-Time Curve (AUC) From The Time of Dosing to The Last Measurable Concentration (AUClast) For Mirabegron
Description	AUClast for mirabegron was reported for the plasma samples collected.
Time Frame	Day 1: predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 72 and 96 hour(s) postdose of each period

Outcome Measure Data

Analysis Population Description

PKAS Population

Arm/Group Title	Mirabegron 25 mg Fed	Mirabegron 25 mg Fasted	Mirabegron 50 mg Fed	Mirabegron 50 mg Fasted
Arm/Group Description	Participants received single dose of 25 mg mirabegron tablet under fed condition orally, on day 1 of either period 1 or period 2.	Participants received single dose of 25 mg mirabegron tablet under fasted condition orally, on day 1 of either period 1 or period 2.	Participants received single dose of 50 mg mirabegron tablet under fed condition orally, on day 1 of either period 1 or period 2.	Participants received single dose of 50 mg mirabegron tablet under fasted condition orally, on day 1 of either period 1 or period 2.
Measure Participants	12	12	12	12
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]	63.3 (36.8)	119 (40.8)	218 (25.4)	369 (39.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 25 mg Fed, Mirabegron 25 mg Fasted
	Comments	Assessment based on an ANOVA performed on natural log-transformed parameters with food condition and period as a fixed effects and participant as a random effect.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geomteric LSMean Ratio
	Estimated Value	53.31
	Confidence Interval	(2-Sided) 90%; 43.02 to 66.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ratios and confidence intervals are transformed back to raw scale & values are expressed as percentages.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg Fed, Mirabegron 50 mg Fasted
	Comments	Assessment based on an ANOVA performed on natural log-transformed parameters with food condition and period as a fixed effects and participant as a random effect.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geomteric LSMean Ratio
	Estimated Value	59.14
	Confidence Interval	(2-Sided) 90%; 49.48 to 70.70
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ratios and confidence intervals are transformed back to raw scale & values are expressed as percentages.

3. Primary Outcome

Title	Maximum Concentration (Cmax) For Mirabegron
Description	Cmax for mirabegron was reported from the plasma samples collected.
Time Frame	Day 1: predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 72 and 96 hour(s) postdose of each period

Outcome Measure Data

Analysis Population Description

PKAS Population

Arm/Group Title	Mirabegron 25 mg Fed	Mirabegron 25 mg Fasted	Mirabegron 50 mg Fed	Mirabegron 50 mg Fasted
Arm/Group Description	Participants received single dose of 25 mg mirabegron tablet under fed condition orally, on day 1 of either period 1 or period 2.	Participants received single dose of 25 mg mirabegron tablet under fasted condition orally, on day 1 of either period 1 or period 2.	Participants received single dose of 50 mg mirabegron tablet under fed condition orally, on day 1 of either period 1 or period 2.	Participants received single dose of 50 mg mirabegron tablet under fasted condition orally, on day 1 of either period 1 or period 2.
Measure Participants	12	12	12	12
Geometric Mean (Geometric Coefficient of Variation) [Nanogram per milliliter (ng/mL)]	3.07 (29.9)	7.88 (82.1)	15.9 (47.7)	33.3 (82.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 25 mg Fed, Mirabegron 25 mg Fasted
	Comments	Assessment based on an ANOVA performed on natural log-transformed parameters with food condition and period as a fixed effects and participant as a random effect.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric LSMean Ratio
	Estimated Value	38.93
	Confidence Interval	(2-Sided) 90%; 26.78 to 56.59
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ratios and confidence intervals are transformed back to raw scale & values are expressed as percentages.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mirabegron 50 mg Fed, Mirabegron 50 mg Fasted
	Comments	Assessment based on an ANOVA performed on natural log-transformed parameters with food condition and period as a fixed effects and participant as a random effect.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric LSMean Ratio
	Estimated Value	47.90
	Confidence Interval	(2-Sided) 90%; 31.76 to 72.24
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ratios and confidence intervals are transformed back to raw scale & values are expressed as percentages.

4. Secondary Outcome

Title	Number of Participants With Adverse Events (AE)
Description	An AE is any untoward medical occurrence in a participant administered an study drug, and which does not necessarily have to have a causal relationship with this study drug. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug whether or not considered related to the study drug. An AE is considered "serious" if, in the view of either the investigator or sponsor, the event results in death, is life-threatening, results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions results in congenital anomaly, or birth defect, requires inpatient hospitalization, other medically important AE. An AE with onset at any time from first dosing until last scheduled procedure was classified as a TEAE.
Time Frame	From date of informed consent signed to end of study (up to 24 days)

Outcome Measure Data

Analysis Population Description

The safety analysis set (SAF) consisted of all participants who received at least 1 dose of study drug.

Arm/Group Title	Mirabegron 25 mg Fed	Mirabegron 25 mg Fasted	Mirabegron 50 mg Fed	Mirabegron 50 mg Fasted
Arm/Group Description	Participants received single dose of 25 mg mirabegron tablet under fed condition orally, on day 1 of either period 1 or period 2.	Participants received single dose of 25 mg mirabegron tablet under fasted condition orally, on day 1 of either period 1 or period 2.	Participants received single dose of 50 mg mirabegron tablet under fed condition orally, on day 1 of either period 1 or period 2.	Participants received single dose of 50 mg mirabegron tablet under fasted condition orally, on day 1 of either period 1 or period 2.
Measure Participants	12	12	12	12
TEAE	2 33.3%	2 33.3%	2 33.3%	2 33.3%
Drug-Related TEAE	1 16.7%	2 33.3%	2 33.3%	1 16.7%
Serious TEAE	0 0%	0 0%	0 0%	0 0%
Drug-Related Serious TEAE	0 0%	0 0%	0 0%	0 0%
TEAE Leading to Death	0 0%	0 0%	0 0%	0 0%
Drug-Related TEAE Leading to Death	0 0%	0 0%	0 0%	0 0%
TEAE Leading to Withdrawal of Treatment	0 0%	0 0%	0 0%	0 0%
Drug-Related TEAE Leading to Withdrawal of Treatment	0 0%	0 0%	0 0%	0 0%
Death	0 0%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	From date of informed consent signed to end of study (up to 24 days)
Arm/Group Title	Mirabegron 25 mg Fed		Mirabegron 25 mg Fasted		Mirabegron 50 mg Fed		Mirabegron 50 mg Fasted
Arm/Group Description	Participants received single dose of 25 mg mirabegron tablet under fed condition orally, on day 1 of either period 1 or period 2.		Participants received single dose of 25 mg mirabegron tablet under fasted condition orally, on day 1 of either period 1 or period 2.		Participants received single dose of 50 mg mirabegron tablet under fed condition orally, on day 1 of either period 1 or period 2.		Participants received single dose of 50 mg mirabegron tablet under fasted condition orally, on day 1 of either period 1 or period 2.
All Cause Mortality
	Mirabegron 25 mg Fed		Mirabegron 25 mg Fasted		Mirabegron 50 mg Fed		Mirabegron 50 mg Fasted
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)
Serious Adverse Events
	Mirabegron 25 mg Fed		Mirabegron 25 mg Fasted		Mirabegron 50 mg Fed		Mirabegron 50 mg Fasted
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Mirabegron 25 mg Fed		Mirabegron 25 mg Fasted		Mirabegron 50 mg Fed		Mirabegron 50 mg Fasted
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/12 (16.7%)		2/12 (16.7%)		2/12 (16.7%)		2/12 (16.7%)
Gastrointestinal disorders
Abdominal pain	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0
Diarrhoea	1/12 (8.3%)	1	0/12 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Investigations
Alanine aminotransferase increased	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Aspartate aminotransferase increased	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Blood uric acid increased	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0
Protein urine present	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Nervous system disorders
Dizziness	0/12 (0%)	0	1/12 (8.3%)	1	1/12 (8.3%)	1	0/12 (0%)	0
Headache	0/12 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.