PMID- 31202957
OWN - NLM
STAT- MEDLINE
DCOM- 20200731
LR  - 20200731
IS  - 1522-9629 (Electronic)
IS  - 1094-5539 (Linking)
VI  - 58
DP  - 2019 Oct
TI  - Efficacy and safety of a first-in-class inhaled PDE3/4 inhibitor (ensifentrine) 
      vs salbutamol in asthma.
PG  - 101814
LID - S1094-5539(19)30038-0 [pii]
LID - 10.1016/j.pupt.2019.101814 [doi]
AB  - INTRODUCTION: This study aimed to investigate the dose-response and pharmacology 
      of a range of single doses of nebulised ensifentrine (RPL554), an inhaled dual 
      phosphodiesterase (PDE) 3/4 inhibitor in patients with asthma. METHODS: In this 
      randomised, placebo-controlled, double-blind crossover study, patients received 
      single nebulised doses of ensifentrine 0.4, 1.5, 6 and 24 mg, salbutamol 2.5 and 
      7.5 mg, and placebo. Eligible patients were adults with asthma, 
      pre-bronchodilator forced expiratory volume in 1 s (FEV(1)) 60-90% predicted and 
      >/=1.5 L, with post-salbutamol FEV(1) increase >/=15%. The co-primary objectives were 
      peak and average FEV(1) over 12 h for ensifentrine vs placebo and salbutamol. 
      Secondary endpoints included: peak and average systolic and diastolic blood 
      pressure, pulse rate and ECG heart rate; and safety and tolerability (adverse 
      events [AEs], and serum potassium). ClinicalTrials.gov: NCT02427165. RESULTS: A 
      total of 29 patients were randomised, with 25 (89%) completing the study. For the 
      two co-primary endpoints there was a clear ensifentrine dose-response 
      relationship, with all treatments superior to placebo (p < 0.001). There was no 
      relationship between the ensifentrine dose and AE incidence or blood pressure. 
      Ensifentrine 0.4, 1.5 and 6 mg had significantly lower effects than both 
      salbutamol doses on pulse and heart rates. Ensifentrine did not impact potassium, 
      whereas there was a was a dose-related reduction for salbutamol. Inhalation of 
      ensifentrine resulted in a dose-related increase in plasma exposure. CONCLUSIONS: 
      Single-dose ensifentrine demonstrated dose-dependent bronchodilation, and was as 
      effective as a therapeutic dose of nebulised salbutamol. All ensifentrine doses 
      were similarly well tolerated, and did not show the characteristic beta(2)-agonist 
      systemic adverse effects.
CI  - Copyright (c) 2019. Published by Elsevier Ltd.
FAU - Bjermer, Leif
AU  - Bjermer L
AD  - Dept of Respiratory Medicine & Allergology, Skane University Hospital, Lund 
      University, Lund, Sweden. Electronic address: leif.bjermer@med.lu.se.
FAU - Abbott-Banner, Katharine
AU  - Abbott-Banner K
AD  - Verona Pharma plc, London, United Kingdom.
FAU - Newman, Kenneth
AU  - Newman K
AD  - Verona Pharma plc, London, United Kingdom.
LA  - eng
SI  - ClinicalTrials.gov/NCT02427165
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20190614
PL  - England
TA  - Pulm Pharmacol Ther
JT  - Pulmonary pharmacology & therapeutics
JID - 9715279
RN  - 0 (Bronchodilator Agents)
RN  - 0 (Isoquinolines)
RN  - 0 (Phosphodiesterase 3 Inhibitors)
RN  - 0 (Pyrimidinones)
RN  - 3E3D8T1GIX (ensifentrine)
RN  - QF8SVZ843E (Albuterol)
SB  - IM
MH  - Administration, Inhalation
MH  - Adult
MH  - Aged
MH  - Albuterol/*pharmacology
MH  - Asthma/*drug therapy
MH  - Bronchodilator Agents/*pharmacology
MH  - Cross-Over Studies
MH  - Double-Blind Method
MH  - Female
MH  - Forced Expiratory Volume/drug effects
MH  - Humans
MH  - Isoquinolines/*pharmacology
MH  - Male
MH  - Middle Aged
MH  - Nebulizers and Vaporizers
MH  - Phosphodiesterase 3 Inhibitors/*pharmacology
MH  - Pyrimidinones/*pharmacology
OTO - NOTNLM
OT  - Asthma
OT  - Phosphodiesterase inhibitors
OT  - Safety
OT  - Spirometry
EDAT- 2019/06/17 06:00
MHDA- 2020/08/01 06:00
CRDT- 2019/06/17 06:00
PHST- 2019/02/01 00:00 [received]
PHST- 2019/05/01 00:00 [revised]
PHST- 2019/06/13 00:00 [accepted]
PHST- 2019/06/17 06:00 [pubmed]
PHST- 2020/08/01 06:00 [medline]
PHST- 2019/06/17 06:00 [entrez]
AID - S1094-5539(19)30038-0 [pii]
AID - 10.1016/j.pupt.2019.101814 [doi]
PST - ppublish
SO  - Pulm Pharmacol Ther. 2019 Oct;58:101814. doi: 10.1016/j.pupt.2019.101814. Epub 
      2019 Jun 14.