PMID- 23497763
OWN - NLM
STAT- MEDLINE
DCOM- 20130829
LR  - 20220408
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 35
IP  - 3
DP  - 2013 Mar
TI  - Effects of food intake on the pharmacokinetic properties of mirabegron oral 
      controlled-absorption system: a single-dose, randomized, crossover study in 
      healthy adults.
PG  - 333-41
LID - S0149-2918(13)00070-2 [pii]
LID - 10.1016/j.clinthera.2013.02.014 [doi]
AB  - BACKGROUND: Mirabegron is a beta3-adrenoceptor agonist used for the treatment of 
      overactive bladder. Mirabegron is formulated as an extended-release tablet using 
      oral controlled-absorption system (OCAS) technology. OBJECTIVE: This study was 
      designed to assess the effects of food on the pharmacokinetic properties of 
      mirabegron OCAS in accordance with regulatory requirements to support dosing 
      recommendations. METHODS: In this single-dose, randomized, open-label, 3-period, 
      parallel-dose-group, crossover study, mirabegron OCAS 50 or 100 mg was 
      administered orally to healthy adult subjects in the fasted state or after a 
      high- or low-fat breakfast. Dose administrations were separated by a washout 
      period of at least 10 days. Blood samples were drawn up to 96 hours after dosing, 
      and plasma concentrations of mirabegron were analyzed by LC/MS-MS. PK properties 
      were determined using noncompartmental methods. Primary end points for the 
      assessment of food effects were Cmax and AUC0-infinity. For tolerability assessment, 
      adverse events (AEs) were monitored using investigators' questionnaires and 
      subjects' spontaneous reports, vital sign measurements, hematology, clinical 
      chemistry, and ECG. RESULTS: Thirty-eight subjects (male, 50%; mean age, 32.1 
      years; mean weight, 77.3 kg; race, 76.3% white) were enrolled in the 50-mg dose 
      group and 38 subjects (male, 52.6%; mean age, 30.9 years; mean weight, 74.5 kg; 
      race, 63.2% white) in the 100-mg dose group. With either fed condition or dose, 
      the 90% CIs for the fed/fasted ratios of both Cmax and AUC0-infinity of mirabegron fell 
      below the predetermined range for bioequivalence (80.0%-125.0%), suggesting that 
      food had no effect on exposure to mirabegron OCAS. With the 50-mg dose, 
      mirabegron Cmax was reduced by 45% with a high-fat breakfast compared with fasted 
      conditions (geometric mean ratio [GMR], 54.8% [90% CI, 43.7%-68.6%]) and AUC0-infinity, 
      by 17% (GMR, 83.2% [90% CI, 74.2%-93.4%]). With the 100-mg dose, mirabegron Cmax 
      and AUC0-infinity were reduced by 39% (GMR, 61.3% [90% CI, 47.8%-78.7%]) and 18% (82.4% 
      [72.6%-93.5%]), respectively, after a high-fat breakfast. With the 50-mg dose, 
      mirabegron Cmax was decreased by 75% (GMR, 25.0% [90% CI, 19.9%-31.3%]) and 
      AUC0-infinity by 51% (48.7% [43.3%-54.7%]) after a low-fat breakfast. Corresponding 
      reductions with the 100-mg dose were 64% (GMR, 36.3% [90% CI, 28.2%-46.8%]) for 
      Cmax and 47% (GMR, 53.2% [90% CI, 46.8%-60.5%]) for AUC0-infinity. The fed/fasted ratios 
      for mirabegron Cmax and AUC0-infinity were in general independent of dose or sex. Food 
      delayed Tmax compared with the fasted state, with similar increases with the 
      high- and low-fat meals (0.9 hours with 50 mg and 1.5-2.0 hours with 100 mg). 
      Mirabegron was generally well tolerated, with no apparent difference in AE 
      frequency between the fasted and fed states. CONCLUSIONS: Mirabegron OCAS tablets 
      exhibited a decrease in mirabegron plasma exposure with food that was independent 
      of dose (50 or 100 mg) or gender but dependent on meal composition. A greater 
      reduction in mirabegron exposure was observed after a low-fat breakfast compared 
      with after a high-fat breakfast. Based on findings from previous studies, the 
      effects of food observed in this study do not warrant dose adjustment in clinical 
      practice. ClinicalTrials.gov identifier: NCT00939757.
CI  - Copyright (c) 2013 Elsevier HS Journals, Inc. All rights reserved.
FAU - Lee, Jennifer
AU  - Lee J
AD  - Astellas Pharma Global Development Inc, Northbrook, IL 60062, USA.
FAU - Zhang, Wenhui
AU  - Zhang W
FAU - Moy, Selina
AU  - Moy S
FAU - Kowalski, Donna
AU  - Kowalski D
FAU - Kerbusch, Virginie
AU  - Kerbusch V
FAU - van Gelderen, Marcel
AU  - van Gelderen M
FAU - Sawamoto, Taiji
AU  - Sawamoto T
FAU - Grunenberg, Nicole
AU  - Grunenberg N
FAU - Keirns, James
AU  - Keirns J
LA  - eng
SI  - ClinicalTrials.gov/NCT00939757
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Acetanilides)
RN  - 0 (Adrenergic beta-Agonists)
RN  - 0 (Thiazoles)
RN  - MVR3JL3B2V (mirabegron)
SB  - IM
MH  - Acetanilides/administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Administration, Oral
MH  - Adrenergic beta-Agonists/administration & dosage/adverse 
      effects/blood/*pharmacokinetics
MH  - Adult
MH  - Cross-Over Studies
MH  - Female
MH  - *Food-Drug Interactions
MH  - Humans
MH  - Male
MH  - Reference Values
MH  - Thiazoles/administration & dosage/adverse effects/blood/*pharmacokinetics
EDAT- 2013/03/19 06:00
MHDA- 2013/08/30 06:00
CRDT- 2013/03/19 06:00
PHST- 2012/10/23 00:00 [received]
PHST- 2013/02/13 00:00 [revised]
PHST- 2013/02/14 00:00 [accepted]
PHST- 2013/03/19 06:00 [entrez]
PHST- 2013/03/19 06:00 [pubmed]
PHST- 2013/08/30 06:00 [medline]
AID - S0149-2918(13)00070-2 [pii]
AID - 10.1016/j.clinthera.2013.02.014 [doi]
PST - ppublish
SO  - Clin Ther. 2013 Mar;35(3):333-41. doi: 10.1016/j.clinthera.2013.02.014.