P113 Efficacy and safety of nalbuphine extended-release in refractory chronic cough: results from the phase 2a RIVER trial
Bibliographic record
Abstract
Introduction and Objectives Refractory chronic cough (RCC) persists despite guideline-based treatment for any comorbid cough-associated conditions and carries a high burden of disease and impact on patients’ lives. Nalbuphine extended-release (NAL ER, oral tablet form) is a kappa receptor agonist and mu receptor antagonist which acts on the cough reflex arc centrally and peripherally, targeting opioid receptors involved in chronic cough. The RIVER trial (NCT05962151) evaluated NAL ER in patients with refractory chronic cough (RCC). Methods This double-blind, placebo (PBO)-controlled, crossover study enrolled patients with RCC stratified into 2 subgroups based on 24-h cough frequency at screening (10–19 coughs/h [moderate] and ≥20 coughs/h [severe]) measured by a cough monitor. Patients were randomly assigned to one of two 21-day treatment sequences: NAL ER to PBO or PBO to NAL ER, with a 21-d washout between treatment periods. NAL ER was titrated every 7 d (27 mg, 54 mg, and 108 mg, all BID). The primary endpoint was relative change from baseline in 24-h objective cough frequency at day 21 in all patients. Results Sixty-six patients were randomized (mean age, 60.2 y; mean cough frequency, 34.7 coughs/h). There was a significant difference in the relative change from baseline in 24-hour cough frequency with NAL ER 108 mg compared to PBO (-65% and -9%, respectively with a PBO-adjusted improvement of 57%; P<.0001; figure 1). Cough frequency subgroups of 10–19 and ≥ 20 coughs/hr achieved PBO-adjusted improvements of 75% and 51%, respectively (both P<.0001), with NAL ER at day 21 (108 mg). Significant reductions in 24-h cough frequency occurred at day 7 with 27-mg NAL ER BID (P<.0001). No serious treatment-emergent adverse events (TEAEs) were reported; 10 patients discontinued treatment due to TEAEs. The most common (≥10%) TEAEs were constipation, somnolence, nausea, dizziness, headache, and fatigue. Conclusions The significant reduction in 24-h cough frequency supports further investigation of NAL ER for RCC.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".