Table 3.

Summary of Studies Reporting on Oliceridine Pharmacological, Analgesic and Adverse Effects

Pharmacological Effects
Onset time15	1 to 2 minutes
Time to peak effect15	6 to 12 minutes
Duration of effect15	1 to 3 hours
Potency compared to morphine16	1: 5
Recommended bolus dose15,16	1 to 2mg every 1 to 3 hours
Recommended PCA regimen15,16	Demand doses of 0.1mg to 0.35mg with 6-minute lockout
	Cumulative daily dose should not exceed 27mg
Metabolism16	Hepatic CYP3A4 and CYP2D6
Metabolites16	No active metabolites
Dose adjustment for renal impairment30	Not needed in end-stage renal disease
Dose adjustment for hepatic impairment30	Not needed for mild (Child-Pugh score 5 to 6) or moderate (Child-Pugh score 7 to 9)
	Reduced dose recommended for severe (Child-Pugh score 10 to 15)
Drug interactions15,16	Caution with CYP3A4 and CYP2D6 inhibitors or inducers
	Caution with SSRIs, TCAs, MAO-I, 5-HT3 antagonists, tramadol
Analgesic Efficacy
Phase I, randomized crossover Healthy volunteers10	Single dose Oliceridine 3mg or 4.5mg; vs morphine 10mg Oliceridine had improved analgesia, quicker onset, and similar duration of action
Phase II, randomized-controlled Patients undergoing bunionectomy20	Oliceridine 0.5mg, 1mg, 2mg, or 3mg q3h; vs morphine 4mg q4h; vs placebo Oliceridine 2mg and 3mg q3h provided superior analgesia than both placebo and morphine 4mg q4h
Phase II, randomized-controlled Patients undergoing abdominoplasty21	Oliceridine loading dose 1.5mg, PCA demand bolus 0.1mg or 0.35mg; vs morphine loading dose 4mg, PCA demand bolus 1mg; vs placebo No significant difference in analgesia between Oliceridine and morphine regimens Oliceridine achieved analgesia faster than morphine
Phase III, randomized-controlled APOLLO-1 Patients undergoing bunionectomy22	Oliceridine loading dose 1.5mg, PCA demand bolus 0.1mg, 0.35mg, or 0.5mg; vs morphine loading dose 4mg, PCA demand bolus 1mg; vs placebo Oliceridine regimens had higher analgesia treatment response than placebo Oliceridine 0.35mg and 0.5mg regimens were non-inferior to morphine 1mg regimen
Phase III, randomized-controlled APOLLO-2 Patients undergoing abdominoplasty23	Oliceridine loading dose 1.5mg, PCA demand bolus 0.1mg, 0.35mg, or 0.5mg; vs morphine loading dose 4mg, PCA demand bolus 1mg; vs placebo Oliceridine and morphine regimens had higher analgesia treatment response than placebo
Phase III, observational ATHENA Surgical and non-surgical patients24	Oliceridine alone, or with multimodal analgesia Rapid onset of analgesia within 30 minutes Less than 5% discontinued due to lack of analgesic efficacy
Adverse Effects
Phase I, randomized crossover Healthy volunteers10	Single dose Oliceridine 3mg or 4.5mg; vs morphine 10mg Oliceridine had less respiratory depression and gastrointestinal complications than morphine
Phase I Healthy volunteers15	Single dose Oliceridine 3mg had no significant effect on QT interval Single dose Oliceridine 6mg associated with transient QT prolongation, without ventricular arrhythmia
Post-hoc analysis Pooled data from APOLLO-1 and APOLLO-225	Oliceridine regimens had lower incidence of respiratory safety events than morphine regimen Oliceridine regimens had less dosage interruptions due to respiratory safety events than morphine
Post-hoc analysis Pooled data from APOLLO-1 and APOLLO-2 and preclinical study26	Oliceridine regimens had better utility (probability of producing analgesia rather than respiratory depression) than morphine
Retrospective study Data from ATHENA trial compared against post hoc control cohort27	Oliceridine had lower incidence of opioid-induced respiratory depression (8.0%, OR 0.14, 95% CI 0.09 to 0.22) than control cohort (30.7%) Subgroup analysis of patients at high risk of respiratory complications: Oliceridine had lower incidence of opioid-induced respiratory depression (OR 0.14, 95% CI 0.09 to 0.22) than control
Post-hoc analysis Data from ATHENA trial28	Factors associated with Oliceridine-induced respiratory depression: baseline pain scores ≥6 (OR 1.9, 95% CI 1.2 to 3.1) and concomitant use of benzodiazepines and/or gabapentinoids (OR 1.6, 95% CI 1.0 to 2.6)
Post-hoc analysis Pooled data from APOLLO-1 and APOLLO-229	Oliceridine regimens achieved higher rate of complete response (no vomiting, no rescue antiemetics) than morphine (bunionectomy: OR 3.14, 95% CI 1.78 to 5.56; abdominoplasty: OR 1.92, 95% CI 1.09 to 3.36)

Abbreviation: PCA, patient-controlled analgesia.