Efficacy and safety of a first-in-class inhaled PDE3/4 inhibitor (ensifentrine) vs salbutamol in asthma
(2019) In Pulmonary Pharmacology and Therapeutics 58.- Abstract
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 (FEV1) 60–90% predicted and ≥1.5 L, with post-salbutamol FEV1 increase ≥15%. The co-primary objectives were peak and average FEV1 over 12 h for ensifentrine vs placebo and salbutamol. Secondary... (More)
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 (FEV1) 60–90% predicted and ≥1.5 L, with post-salbutamol FEV1 increase ≥15%. The co-primary objectives were peak and average FEV1 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 β2-agonist systemic adverse effects.
(Less)
- author
- Bjermer, Leif LU ; Abbott-Banner, Katharine and Newman, Kenneth
- organization
- publishing date
- 2019-10
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Asthma, Phosphodiesterase inhibitors, Safety, Spirometry
- in
- Pulmonary Pharmacology and Therapeutics
- volume
- 58
- article number
- 101814
- publisher
- Elsevier
- external identifiers
-
- scopus:85069689303
- pmid:31202957
- ISSN
- 1094-5539
- DOI
- 10.1016/j.pupt.2019.101814
- language
- English
- LU publication?
- yes
- id
- 7255de8e-c1e8-49c0-be3f-8ecb42ebb0af
- date added to LUP
- 2019-08-02 13:23:37
- date last changed
- 2024-09-19 07:03:36
@article{7255de8e-c1e8-49c0-be3f-8ecb42ebb0af, abstract = {{<p>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<sub>1</sub>) 60–90% predicted and ≥1.5 L, with post-salbutamol FEV<sub>1</sub> increase ≥15%. The co-primary objectives were peak and average FEV<sub>1</sub> 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 β<sub>2</sub>-agonist systemic adverse effects.</p>}}, author = {{Bjermer, Leif and Abbott-Banner, Katharine and Newman, Kenneth}}, issn = {{1094-5539}}, keywords = {{Asthma; Phosphodiesterase inhibitors; Safety; Spirometry}}, language = {{eng}}, publisher = {{Elsevier}}, series = {{Pulmonary Pharmacology and Therapeutics}}, title = {{Efficacy and safety of a first-in-class inhaled PDE3/4 inhibitor (ensifentrine) vs salbutamol in asthma}}, url = {{http://dx.doi.org/10.1016/j.pupt.2019.101814}}, doi = {{10.1016/j.pupt.2019.101814}}, volume = {{58}}, year = {{2019}}, }