Oliceridine for the Management of Moderate to Severe Acute Postoperative Pain: A Narrative Review

Figures & data

Figure 1 Flowchart summarizing literature search results for all studies related to oliceridine.

Figure 2 Risk of bias assessment for phase II and III randomized clinical trials.

Table 1 Summary of Results for Phase II and III Studies

Study	Subjects Treated	Surgery Type	Dosing Regimen	Efficacy	Respiratory Depression	PONV
Phase 2a, Viscusi 2016^Citation38	141 (Pilot Phase), 192 (Phase 2)	Bunionectomy	Oliceridine IV Bolus: 1, 2, 3, or 4mg IV q4h (Pilot Phase); 0.5, 1, 2, or 3mg IV q3h (Phase 2) Morphine IV Bolus: 4mg q4h	Least-squares mean reduction in time-weighted average change in NRS over a 48-hour period: −0.5, −0.3, −1.4 and −2.4 (Oliceridine Phase 2) vs −1.3 (Morphine)	Integrated mean percent change from baseline in oxygen saturation over 0 to 24.5 hours: −1.5, −0.5, −2.3, and −5.1%·hour (Oliceridine Phase 2) vs −14.5%·hour (Morphine)	Nausea: 35, 34.2, 55.6, and 74.2% (Oliceridine Phase 2) vs 56.4% (Morphine) Vomiting: 0, 0, 10.5, 27.8, and 54.8% (Oliceridine Phase 2) vs 30.8% (Morphine)
Phase 2b, Singla 2017^Citation39	200	Abdominoplasty	Oliceridine PCA: Two loading doses of 0.75mg separated by 10 minutes that were followed by demand doses of 0.1mg (A) or 0.35mg (B) with a 6-minute lockout interval Morphine PCA: Two loading doses of 2mg separated by 10 minutes that were followed by demand doses of 1mg with a 6-minute lockout interval	Time-weighted average change in NPRS over a 24-hour period relative to placebo: 2.3 and 2.1 points (Oliceridine) vs 2.1 points (Morphine)	Hypoxia, Bradypnea, Decreased respiratory effort, or Hypoventilation: 15 and 31% (Oliceridine) vs 53% (Morphine)	Nausea: 41 and 46% (Oliceridine) vs 72% (Morphine) Vomiting: 15 and 15% (Oliceridine) vs 42% (Morphine)
Phase 3 APOLLO-1, Viscusi 2019^Citation41	389	Bunionectomy	Oliceridine PCA: Loading dose of 1.5mg followed by demand doses of 0.1, 0.35, or 0.5mg with a 6-minute lockout interval Morphine PCA: Loading dose of 4mg followed by demand doses of 1mg with a 6-minute lockout interval	Percentage of treatment responders: 50, 62, and 65.8% (Oliceridine) vs 71.1% (Morphine)	Respiratory safety burden: 0.04, 0.28, and 0.8 hours (Oliceridine) vs 1.1 hours (Morphine)	Gastrointestinal adverse events: 40.8, 59.5, and 70.9% (Oliceridine) vs 72.4% (Morphine)
Phase 3 APOLLO-2, Singla 2019^Citation42	401	Abdominoplasty	Oliceridine PCA: Loading dose of 1.5mg followed by demand doses of 0.1, 0.35, or 0.5mg with a 6-minute lockout interval Morphine PCA: Loading dose of 4mg followed by demand doses of 1mg with a 6-minute lockout interval	Percentage of treatment responders: 61, 76.3, and 70% (Oliceridine) vs 78.3% (Morphine)	Respiratory safety burden: 0.43, 1.48, and 1.59 hours (Oliceridine) vs 1.72 hours (Morphine)	Gastrointestinal adverse events: 49.4, 65.8, and 78.8% (Oliceridine) vs 79.3% (Morphine)
Phase 3 ATHENA, Bergese 2019^Citation43	768	Both surgical and non-surgical patients with painful medical conditions	Oliceridine IV Bolus: Loading dose of 1 to 2mg and a supplemental dose of 1mg within 15 minutes if needed, followed by doses of 1 to 3mg every 1 to 3 hours as needed Oliceridine PCA: Loading dose of 1.5mg and demand doses of 0.5mg with a 6-minute lockout interval, and supplemental doses of 1mg could be given as needed	Reduction in NRS pain score within 30 minutes: 2.2 points	Oxygen saturation <90%: 5.5%	Nausea: 31% Vomiting: 10%

Viscusi ER, Webster L, Kuss M, et al. A randomized, Phase 2 study investigating TRV130, a biased ligand of the μ-opioid receptor, for the intravenous treatment of acute pain. Pain. 2016;157(1):264–272. doi:10.1097/j.pain.0000000000000363

 PubMed Web of Science ®Google Scholar

Singla N, Minkowitz HS, Soergel DG, et al. A randomized, Phase IIb study investigating oliceridine (TRV130), a novel µ-receptor G-protein pathway selective (μ-GPS) modulator, for the management of moderate to severe acute pain following abdominoplasty. J Pain Res. 2017;10:2413–2424. doi:10.2147/JPR.S137952

 PubMed Web of Science ®Google Scholar

Viscusi ER, Skobieranda F, Soergel DG, Cook E, Burt DA, Singla N. APOLLO-1: a randomized placebo and active-controlled phase III study investigating oliceridine (TRV130), a G protein-biased ligand at the µ-opioid receptor, for management of moderate-to-severe acute pain following bunionectomy. J Pain Res. 2019;12:927–943. doi:10.2147/JPR.S171013

 PubMed Web of Science ®Google Scholar

Singla NK, Skobieranda F, Soergel DG, et al. APOLLO-2: a randomized, placebo and active-controlled phase iii study investigating oliceridine (TRV130), a G protein-biased ligand at the μ-opioid receptor, for management of moderate to severe acute pain following abdominoplasty. Pain Pract. 2019;19(7):715–731. doi:10.1111/papr.12801

 PubMed Web of Science ®Google Scholar

Bergese SD, Brzezinski M, Hammer GB, et al. ATHENA: a Phase 3, open-label study of the safety and effectiveness of oliceridine (TRV130), A G-protein selective agonist at the µ-opioid receptor, in patients with moderate to severe acute pain requiring parenteral opioid therapy. J Pain Res. 2019;12:3113–3126. doi:10.2147/JPR.S217563

 PubMed Web of Science ®Google Scholar