Anti-inflammatory effect of a novel inhaled dual PDE3/4 inhibitor RPL554 in man, a unique "first-in-class" drug for the treatment of COPD & asthma
Bibliographic record
Abstract
Background: Current bronchodilators have limited efficacy in severe COPD & asthma & the neutrophilic inflammation is not well treated. RPL554 is a novel, well tolerated dual PDE 3/4 inhibitor with significant bronchodilator properties in COPD & asthma, bronchoprotective effects in asthmatics & is anti-inflammatory pre-clinically. Aim: To evaluate the effect of RPL554 on inhaled lipopolysaccharide (LPS)-induced neutrophilia in sputum. Methods: In a randomised, double-blind, placebo (PBO)-controlled crossover study in 21 healthy subjects, RPL554 (0.018mg/kg)was inhaled using a jet nebuliser via an oro-nasal mask o.d for 6 days. On day 6 an inhaled LPS challenge was performed 1h post RPL554 or PBO using a Mefar dosimeter. Sputum was induced 6 & 24h post-LPS & cells/g sputum calculated. Results: RPL554 statistically significantly reduced total & individual cells, 6h post LPS vs PBO (Table 1). RPL554 was well-tolerated with AE’s being generally mild, transient & not different from PBO. RPL554’s PK properties were reproducible over 6 days. Table 1. Cells/g sputum Cells (x10 6 /g sputum) RPL554 PBO p value Neutrophils 6.81 11.38 0.002 Macrophages 1.16 1.58 0.044 Eosinophils 0.014 0.025 0.001 Lymphocytes 0.014 0.042 0.001 Bronchial cells 0.110 0.095 0.622 Total cells 8.66 13.57 0.002 Conclusions: RPL554 produced significant airway anti-inflammatory effects, including reducing neutrophil infiltration & is the first drug demonstrating bronchodilator & anti-inflammatory properties in one molecule. RPL554 is thus a promising “bifunctional” first in class treatment for patients with COPD or asthma and not well controlled on existing treatment.
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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".