TABLE 4.
Efficacy outcomes of patients enrolled in stage 2 (FAS).
| Placebo (n = 20) | HSK21542-0.5 μg/kg group (n = 20) | HSK21542-1.0 μg/kg group (n = 20) | P-value | |
| SPID0–24 h (scores × min) | 0.406 | |||
| Mean (SD) | −772.9 (3,108.1) | −2,026.6 (2,667.5) | −1,850.8 (2,169.6) | |
| Median (range) | −1,192.0 (−8,926–3,606) | −1,502.0 (−7,472–3,939) | −1,660.0 (−6,311–2,168) | |
| SPID0–12 h (scores × min) | 0.518 | |||
| Mean (SD) | −223.3 (1,544.0) | −791.1 (1,189.7) | −719.8 (1,142.6) | |
| Median (range) | −258.5 (−4,556–1902) | −716.5 (−2,826–2,091) | −675.0 (−2,824–1,922) | |
| PID (scores × min) | ||||
| LSMD vs. placebo (95% CI) | 0.45 (−0.21, 1.10) | 0.59 (−0.03, 1.20) | ||
| P-value vs. placebo* | 0.175 | 0.061 | ||
| Patients administered with morphine 0–12 h after first dosing of experimental drugs, n (%) | 10 (50.0) | 6 (30.0) | 4 (20.0) | 0.123 |
| Cumulative dosage of morphine 0–12 h after first dosing of the experimental drugs (mg) | 0.115 | |||
| Mean (SD) | 2.5 (3.4) | 1.3 (2.3) | 0.9 (2.0) | |
| Median (range) | 1.5 (0–11) | 0.0 (0–8) | 0.0 (0–8) | |
| Patients administered with morphine during 0–24 h after first dosing of experimental drugs, n (%) | 10 (50.0) | 6 (30.0) | 4 (20.0) | 0.123 |
| Cumulative dose of morphine 0–24 h after first dosing of the experimental drugs (mg) | 0.109 | |||
| Mean (SD) | 3.0 (4.2) | 1.5 (2.5) | 0.9 (2.0) | |
| Median (range) | 1.5 (0–11) | 0.0 (0–8) | 0.0 (0–8) | |
| Time of first injection of morphine (min) | 0.883 | |||
| Mean (SD) | 78.2 (81.9) | 103.9 (134.5) | 133.6 (120.3) | |
| Median (range) | 59.6 (1.9–286.3) | 61.7 (4.1–362.5) | 129.1 (15.3–260.9) | |
| Patients with NRS ≤ 3 during 0–12 h administration, n (%) | 10 (50.0) | 12 (60.0) | 14 (70.0) | 0.435 |
| Patients with NRS ≤ 3 during 0–24 h administration, n (%) | 10 (50.0) | 12 (60.0) | 14 (70.0) | 0.435 |
| Analgesia duration (min) | 0.210 | |||
| Mean (SD) | 1,306.2 (234.6) | 1,324.8 (173.0) | 1,406.2 (68.1) | |
| Median (range) | 1,420.2 (623.0–1,463.8) | 1,409.9 (836.0–1,442.4) | 1,422.9 (1,212.0–1,496.0) | |
| Satisfaction score for patients | 0.377 | |||
| Mean (SD) | 9.1 (1.3) | 8.7 (1.8) | 9.4 (1.1) | |
| Median (range) | 9.5 (6–10) | 9.0 (5–10) | 10.0 (6–10) | |
| Satisfaction score for clinician | 0.290 | |||
| Mean (SD) | 8.6 (2.0) | 8.3 (1.7) | 9.1 (1.5) | |
| Median (range) | 10.0 (4–10) | 9.0 (5–10) | 10.0 (6–10) | |
*Data were compared using mixed model repeated measures (MMRM) methods, with the baseline pain score, treatment, time point and interaction between treatment and time point as fixed effects, and patients as random effects. Statistical significance was defined as a two-sided alpha level of P < 0.05. For HSK21542 dose groups in stage 2: HSK21542-0.5 μg/kg or HSK21542-1.0 μg/kg were administered at postoperative 0 h, 8 h and 16 h. AUC, area under curve; LSMD, least squares mean difference; NRS, numerical rating scale; PID, pain intensity difference; SD, standard deviation; SPID0–12 h, time-weighted summed pain intensity differences over 12 h; SPID0–24 h, time-weighted summed pain intensity differences over 24 h.