Bronchodilator effect of a novel inhaled dual PDE3/4 inhibitor, RPL554, in mild allergic asthma & rhinitis
Bibliographic record
Abstract
Background: RPL554 is a novel inhaled dual phosphodiesterase (PDE) 3 & 4 inhibitor with long-acting bronchodilator & anti-inflammatory effects in preclinical models. Aims and Objectives: To evaluate RPL554 safety & efficacy in mild allergic asthma & rhinitis. Methods: In 2 randomised, double-blind, placebo-controlled, crossover trials, 10 mild allergic asthmatics (M; 20-50y; FEV1: 82-112%prd; PC20Mch: 0.07-1.49mg/mL; SABA prn only) and 10 allergic rhinitics (M; 19-44y; 6 with co-existing asthma; FEV1: 83-128%prd) were studied. In asthmatics, a methacholine challenge (PC20Mch) was done 1h from nebulisation start to assess bronchoprotection. Using a jet nebuliser, RPL554 0.018mg/kg was inhaled 10min via an oro-nasal mask. Standard safety & pharmacokinetic measurements were at predetermined times from nebulisation start with spirometry at pre-dose & regularly for 24h. Bronchodilation was assessed by FEV1 changes. Results: RPL554 was well-tolerated. Adverse events were mild, transient & generally of equal frequency in RPL554 & placebo groups with no significant changes in heart rate or systemic blood pressure noted. In asthmatics, RPL554 produced rapid, sustained bronchodilation, with a mean maximal FEV1 increase of 520mL (95%CI: 320-720mL; p<0.0001) or 15% increase from baseline vs. placebo. It also increased PC20MCh by mean 1.5 doubling doses (95%CI: 0.63– 2.3; p=0.004). In rhinitics, a maximal bronchodilator response occurred between 30min & 3h with a mean maximal FEV1 increase of 300mL or 7.5% increase (95%CI: 90-310mL; p=0.004). Conclusions: RPL554 produced safe, rapid, long-lasting bronchodilation in mild allergic asthmatics & rhinitics, with bronchoprotection in asthmatics.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".