TAK-925 (Danavorexton), an Orexin Receptor 2 Agonist, Reduces Opioid-induced Respiratory Depression and Sedation without Affecting Analgesia in Healthy Men
Authors' conclusion
Danavorexton has effects on respiration and wakefulness in an opioid-induced respiratory depression setting without reversing opioid analgesia.
Study context
- Population
- Healthy men in a remifentanil-induced respiratory depression model (isohypercapnic, ≈30 to 40% decrease in minute ventilation)crossover
- Participants
- 13 men
- Comparison
- Danavorexton vs placebo under remifentanil infusion
Methodological detailssingle-centre, double-blind, placebo-controlled, two-way crossover, phase 1
- Single-centre
- Double-blind
- Placebo-controlled
- Two-way crossover
- Phase 1
Primary result
As reported in the abstract
Ventilation variables (observed mean change vs placebo)
Each group vs placeboMean change, minute volume, l/min (95% CI)P value
Danavorexton low-dose
8.2(5.0–11.4)
P < 0.001Danavorexton high-dose
13.0(9.4–16.5)
P < 0.001Each group vs placeboMean change, tidal volume, ml (95% CI)P value
Danavorexton low-dose
312(180–443)
P < 0.001Danavorexton high-dose
483(309–657)
P < 0.001Each group vs placeboMean change, respiratory rate, breaths/min (95% CI)P value
Danavorexton low-dose
3.8(1.9–5.7)
P < 0.001Danavorexton high-dose
5.2(2.7–7.7)
P < 0.001Further findings
| Outcome | Mean change (mm) (95% CI) | P value | |
|---|---|---|---|
| Sedation (VAS)Danavorexton high-dose vs Placebo | −29.7 (−54.1 to −5.3) | P < 0.001 | |
| −100−50050Difference, mm (linear scale) |
| Outcome | Mean change (95% CI) | P value | |
|---|---|---|---|
| Sedation (RASS)Danavorexton high-dose vs Placebo | 0.4 (0.0–0.7) | P < 0.001 | |
| −0.500.51Difference (linear scale) |
| Outcome | P value |
|---|---|
| Pain toleranceDanavorexton low-dose vs Placebo | P = 0.491 |
| Pain toleranceDanavorexton high-dose vs Placebo | P = 0.140 |
Pain tolerance
- No significant differences between danavorexton doses or vs placebo (≈13% increase from baseline)
Safety
Treatment-emergent adverse events (all mild)
- Treatment-emergent adverse events (all mild) — Insomnia lasting 1 day, related to danavorexton
- 1
Original publication
TAK-925 (Danavorexton), an Orexin Receptor 2 Agonist, Reduces Opioid-induced Respiratory Depression and Sedation without Affecting Analgesia in Healthy Men. Anesthesiology. Published 13 January 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →