Randomised clinical trial: the long‐term safety and tolerability of naloxegol in patients with pain and opioid‐induced constipation
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
BACKGROUND: Opioid-induced constipation (OIC) is a common adverse effect of opioid therapy. AIM: To evaluate the long-term safety and tolerability of naloxegol, an oral, peripherally acting μ-opioid receptor antagonist (PAMORA), in patients with noncancer pain and OIC. METHODS: A 52-week, multicenter, open-label, randomised, parallel-group phase 3 study was conducted in out-patients taking 30-1000 morphine-equivalent units per day for ≥4 weeks. Patients were randomised 2:1 to receive naloxegol 25 mg/day or usual-care (UC; investigator-chosen laxative regimen) treatment for OIC. RESULTS: The safety set comprised 804 patients (naloxegol, n = 534; UC, n = 270). Mean exposure duration was 268 days with naloxegol and 297 days with UC. Frequency of adverse events (AEs) was 81.8% with naloxegol and 72.2% with UC. Treatment-emergent AEs occurring more frequently for naloxegol vs. UC were abdominal pain (17.8% vs. 3.3%), diarrhoea (12.9% vs. 5.9%), nausea (9.4% vs. 4.1%), headache (9.0% vs. 4.8%), flatulence (6.9% vs. 1.1%) and upper abdominal pain (5.1% vs. 1.1%). Most naloxegol-emergent gastrointestinal AEs occurred early, resolving during or after naloxegol discontinuation and were mild or moderate in severity; 11 patients discontinued due to diarrhoea and nine patients owing to abdominal pain. Pain scores and mean daily opioid doses remained stable throughout the study; no attributable opioid withdrawal AEs were observed. Two patients in each group had an adjudicated major adverse cardiovascular event unrelated to study drug; no AEs were reported nor adjudicated as bowel perforations. CONCLUSION: In patients with noncancer pain and opioid-induced constipation, naloxegol 25 mg/day up to 52 weeks was generally safe and well tolerated.
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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 | 0.002 | 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 it