PMID- 29763659
OWN - NLM
STAT- MEDLINE
DCOM- 20190207
LR  - 20221207
IS  - 1522-9629 (Electronic)
IS  - 1094-5539 (Linking)
VI  - 51
DP  - 2018 Aug
TI  - Safety and pharmacokinetics of budesonide/glycopyrronium/formoterol fumarate 
      dihydrate metered dose inhaler (BGF MDI) in healthy adult subjects of Japanese 
      descent.
PG  - 18-25
LID - S1094-5539(18)30034-8 [pii]
LID - 10.1016/j.pupt.2018.05.001 [doi]
AB  - INTRODUCTION: BGF MDI, a budesonide, glycopyrronium, and formoterol fumarate 
      dihydrate triple fixed-dose combination metered dose inhaler formulated using 
      co-suspension delivery technology, is currently in Phase III global development 
      for chronic obstructive pulmonary disease. METHODS: This was a Phase I, 
      randomized, double-blind, placebo-controlled, ascending-dose, crossover study to 
      assess the safety and pharmacokinetic profiles of two doses of BGF MDI in healthy 
      adult subjects of Japanese descent (NCT02197975). Safety assessments included 
      monitoring for adverse events (AEs). Pharmacokinetic parameters were assessed 
      following a single dose and 7-days chronic dosing with BGF MDI 160/14.4/10 mug and 
      BGF MDI 320/14.4/10 mug. RESULTS: Twenty subjects were randomized and included in 
      the safety and pharmacokinetic populations; mean age 29.7 years; 65% male; and 
      mean body mass index of 21.9 kg/m(2). The incidences of treatment-emergent AEs 
      (TEAEs) were similar between treatments. All the TEAEs were mild to moderate in 
      severity. Budesonide area under the plasma concentration-time curve from 0 to 
      12 h (AUC(0-12)) and maximum observed plasma concentration (C(max)) values were 
      approximately double for the higher dose of BGF MDI compared with the lower dose 
      on Day 1 and also following chronic dosing on Day 8. Glycopyrronium and 
      formoterol AUC(0-12) and C(max) values on Day 8 were comparable between the two 
      doses of BGF MDI. DISCUSSION: Both doses of BGF MDI were well tolerated in 
      healthy subjects of Japanese descent and the systemic exposure to budesonide was 
      dose proportional for BGF MDI 160/14.4/10 mug and BGF MDI 320/14.4/10 mug. The 
      safety and pharmacokinetics for BGF MDI 160/14.4/10 mug and BGF MDI 320/14.4/10 mug 
      in Japanese subjects were comparable to data from previous studies in Western 
      populations, which suggests that the safety and efficacy profile of BGF MDI 
      should be similar in Western and Japanese subjects.
CI  - Copyright (c) 2018 Pearl \\u0013 a member of the AstraZeneca group. Published by 
      Elsevier Ltd.. All rights reserved.
FAU - Dorinsky, Paul
AU  - Dorinsky P
AD  - Pearl - a Member of the AstraZeneca Group, 4222 Emperor Blvd, Suite 560, Durham, 
      NC 27703, USA. Electronic address: paul.dorinsky1@astrazeneca.com.
FAU - DePetrillo, Paolo
AU  - DePetrillo P
AD  - Pharmaron, 800 West Baltimore Street, Baltimore, MD 21201, USA. Electronic 
      address: paolo.depetrillo@pharmaron-us.com.
FAU - Siddiqui, Shahid
AU  - Siddiqui S
AD  - AstraZeneca, One MedImmune Way, Gaithersburg, MD 20878, USA. Electronic address: 
      shahid.siddiqui@astrazeneca.com.
FAU - Maes, Andrea
AU  - Maes A
AD  - Pearl - a Member of the AstraZeneca Group, 280 Headquarters Plaza, East Tower, 
      2nd Floor, Morristown, NJ 07960, USA. Electronic address: 
      andrea.maes@astrazeneca.com.
FAU - Reisner, Colin
AU  - Reisner C
AD  - AstraZeneca, One MedImmune Way, Gaithersburg, MD 20878, USA; Pearl - a Member of 
      the AstraZeneca Group, 280 Headquarters Plaza, East Tower, 2nd Floor, Morristown, 
      NJ 07960, USA. Electronic address: colin.reisner@astrazeneca.com.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180512
PL  - England
TA  - Pulm Pharmacol Ther
JT  - Pulmonary pharmacology & therapeutics
JID - 9715279
RN  - 0 (Bronchodilator Agents)
RN  - 0 (Drug Combinations)
RN  - 0 (Muscarinic Antagonists)
RN  - 51333-22-3 (Budesonide)
RN  - V92SO9WP2I (Glycopyrrolate)
RN  - W34SHF8J2K (Formoterol Fumarate)
SB  - IM
MH  - Administration, Inhalation
MH  - Adult
MH  - Area Under Curve
MH  - Asian People
MH  - Bronchodilator Agents/*administration & dosage/adverse effects/pharmacokinetics
MH  - Budesonide/*administration & dosage/adverse effects/pharmacokinetics
MH  - Cross-Over Studies
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Combinations
MH  - Female
MH  - Formoterol Fumarate/*administration & dosage/adverse effects/pharmacokinetics
MH  - Glycopyrrolate/*administration & dosage/adverse effects/pharmacokinetics
MH  - Humans
MH  - Male
MH  - Metered Dose Inhalers
MH  - Muscarinic Antagonists/administration & dosage/adverse effects/pharmacokinetics
MH  - Young Adult
OTO - NOTNLM
OT  - Chronic obstructive pulmonary disease
OT  - Co-suspension delivery technology
OT  - ICS/LAMA/LABA
OT  - Japanese
OT  - Triple fixed-dose combination
OT  - Western
EDAT- 2018/05/16 06:00
MHDA- 2019/02/08 06:00
CRDT- 2018/05/16 06:00
PHST- 2018/02/05 00:00 [received]
PHST- 2018/04/20 00:00 [revised]
PHST- 2018/05/11 00:00 [accepted]
PHST- 2018/05/16 06:00 [pubmed]
PHST- 2019/02/08 06:00 [medline]
PHST- 2018/05/16 06:00 [entrez]
AID - S1094-5539(18)30034-8 [pii]
AID - 10.1016/j.pupt.2018.05.001 [doi]
PST - ppublish
SO  - Pulm Pharmacol Ther. 2018 Aug;51:18-25. doi: 10.1016/j.pupt.2018.05.001. Epub 
      2018 May 12.