Table 1.

Clinical safety and efficacy

Author (year)	Groups studied and intervention	Results and findings	Conclusions
Viscusi et al. (2015) [35]	Phase 2, randomized, double-blind, adaptive-design study assessing the efficacy and tolerability of TRV130 in postoperative bunionectomy patients. The first phase tested 1, 2, 3, or 4 mg IV TRV130 q4h against placebo IV q4h and 4 mg morphine IV q4h. The second phase tested 0.5, 1, 2, or 3 mg q3h against placebo IV q4h and 4 mg morphine IV q4h	In the first phase, 2 and 3 mg TRV130 showed better NRS TWA0-48 reductions than placebo, similar to morphine. In the second phase, TRV130 3 mg was more statistically efficacious than morphine 4 mg. No SAEs occurred in either phase of the study for TRV130; though some SEs were found (nausea, dizziness, headache, and vomiting). TRV130 showed a smaller effect on oxygen saturation than morphine did	TRV130 showed statistically significant pain reduction compared to placebo and morphine, with no SAEs and decreased effect on oxygen saturation
Soergel et al. (2014) [33, 34]	Single-site study evaluating the safety, tolerability, and pharmacological properties of increasing TRV130 doses (0.15–7 mg IV) in healthy subjects, the impact of poor cytochrome P450 2D6 (CYP2D6) metabolism on TRV130, and the tolerability of short infusions	TRV130 was well tolerated, with moderate AEs only in the 7 mg dosing group. Plasma concentrations were highest at the end of the 1-h infusion, declining in multiple phases, indicating more than one distribution compartment. CYP2D6 poor metabolizers had a TRV130 Cmax 1.35 times higher and clearance that was ~ 50% lower than normal metabolizer counterparts. 1-, 5-, 15-, and 30-min 1.5 mg TRV130 infusions were well tolerated	TRV130 was well tolerated, plasma concentrations, and relatively low SE profile. CYP2D6 poor metabolizers had significantly altered pharmacokinetics and indicate multiple distribution compartments
Soergel et al. (2014) [33, 34]	Single-center, double-blind, randomized, placebo-controlled, crossover study that evaluated µ-opioid receptor TRV130 agonism against placebo or morphine IV for analgesia, safety, and tolerability in healthy male individuals. The subjects received single doses of TRV130, morphine IV, or placebo on odd days for 10 days	TRV130 infusions were associated with decreased SE profile up to 4.5 mg, where the SEs of TRV130 were similar to those associated with morphine IV; while producing an equivalent analgesic effect. TRV130 induced a temporary decrease in respiratory drive that was markedly decreased from the morphine-induced respiratory drive that persisted through 4 h post-infusion	TRV130 showed higher peak analgesia compared to morphine, along with reduced SE profile ,and was generally well tolerated
Singla et al. (2019) [36]	A phase 3, double-blind, randomized placebo- and active-controlled study evaluating the safety and efficacy of oliceridine in treating abdominoplasty-related pain. The patients in the study received a loading dose of oliceridine 1.5 mg, morphine 4 mg, or placebo IV, which was then followed by demand doses of 0.1, 0.35, and 0.5 mg either self- or clinician-administered	All treatment groups except for the placebo group showed a markedly decreased need for rescue doses during the treatment. The placebo group showed the highest occurrence of rescue pain medication use. Oliceridine-related SAEs were limited to syncope and lethargy during the study, while the other observed SAEs during treatment were thought to be related to other factors. GI AEs showed a proportional dose-related relationship with oliceridine use up to the 0.5 mg oliceridine dose, where the incidence of GI AEs was similar to the morphine group	Oliceridine was shown to be an effective and relatively safe IV analgesic for the treatment of postoperative pain related to abdominoplasty

AE adverse event, GI gastrointestinal, NRS numeric rating scale, SAE serious adverse event, SE side effect