University of Mississippi eGrove

Annual Poster Session Pharmacy, School of

10-23-2020

R22. Oliceridine’s role in pain management: a qualitative literature review

Hallie Austin University of Mississippi, [email protected]

Melissa Reilly University of Mississippi

Follow this and additional works at: https://egrove.olemiss.edu/pharm_annual_posters

Recommended Citation Austin, Hallie and Reilly, Melissa, "R22. Oliceridine’s role in pain management: a qualitative literature review" (2020). Annual Poster Session. 22. https://egrove.olemiss.edu/pharm_annual_posters/22

This Book is brought to you for free and open access by the Pharmacy, School of at eGrove. It has been accepted for inclusion in Annual Poster Session by an authorized administrator of eGrove. For more information, please contact [email protected]. OLICERIDINE’S ROLE IN PAIN MANAGEMENT: A QUALITATIVE LITERATURE REVIEW

Melissa Reilly, PharmD, BCGP, Hallie Austin, PharmD candidate 2023 INTRODUCTION

• Oliceridine (Olinvyk) is a novel opioid for moderate to severe pain management for use in the clinical setting. • As an opioid agonist, it is relatively selective for the mu- opioid receptor, and it serves as the first mu-opioid receptor G protein pathway selective modulator. • With its novel mechanism of action, oliceridine was designed to improve μ-opioid receptor pharmacology and decrease opioid related adverse effects. OBJECTIVES

This literature review sought to identify the role oliceridine may have in pain management in clinical practice. • Study design • Qualitative literature review METHODS • 2014-2019 • Search terms • PubMed - “oliceridine” METHODS

INCLUSION CRITERIA EXCLUSION CRITERIA

Randomized control trial Review articles

Open label Pharmacokinetic & pharmacodynamic modeling trials RESULTS: RESULTS 41studies populated from “oliceridine” search 6 studies included 35 studies excluded Reason for exclusion:

Animal PK/PD Review study study articles 10 8 17 Study Baseline Intervention Controls Results Characteristics

Singla, et al.1 No. 401 (loading dose, Placebo Respiratory Safety Burden: O vs. placebo (efficacy) Age 18 – 75 demand dose) Oliceridine vs placebo: P > 0.05 O 0.1 mg: P = 0.029 2019 O: Morphine vs. placebo: P < 0.05 O 0.35 mg: P < 0.0001 1.5 mg, 0.1 mg O 0.5 mg: P = 0.0004 1.5 mg, 0.35 mg GI adverse effects: 1.5 mg, 0.5 mg O: 0.1 mg: 49.4%; 0.35 mg: 65.8%; M (1 mg) vs. placebo 0.5 mg: 78.8% 78.3% (P < 0.001) M: placebo: 47.0% 4 mg, 1 mg M: 79.3%

Bergese, et No. 768 O: placebo The incidence of AEs leading to rapid reduction in NRS pain score by 2.2 ± 2.3 at al.2 Age 18 - 89 0.9 to 223.5 mg early discontinuation and serious 30 mins from a score of 6.3 ± 2.1 (at baseline) 2019 AEs were 2% and 3%, respectively. which was maintained to the end of treatment.

Viscusi, et No. 389 (loading dose, placebo Respiratory Safety Burden: O vs. placebo: all P<0.0001 al.3 Age 18 - 75 demand dose) -supplemental oxygen: 2019 O: O vs M % treatment responders: 1.5 mg, 0.1 mg P<0.01 Placebo: 15.2% 1.5 mg, 0.35 mg O 0.1 mg: 50% 1.5 mg, 0.5 mg GI adverse effects: O 0.35 mg: 62% O vs M O 0.5 mg: 65.8% M: P<0.05 M 1 mg: 71.1% 4 mg, 1 mg

O: oliceridine M: morphine Study Baseline Intervention Controls Results Characteristics

Singla, et al.4 No. 200 (loading dose, demand dose) Placebo O 0.1 mg vs placebo: P=0.0001 2017 (Oct) Age 18-65 O: O 0.35 mg vs placebo: P=0.0005 A: 1.5 mg, 0.1 mg (n=39) B: 1.5 mg, 0.35 mg (n=39) M vs placebo: P<0.0001

M: O 0.1 and 0.35 mg vs M 1 mg: 4 mg, 1 mg (n=83) Nausea: P<0.01 Vomiting: P<0.01 Respiratory effects: P<0.05

Viscusi, et al. 5 No. 400 O: 0.5, 1, 2, & 3 mg Placebo O v Placebo 2016 Age 18-75 O 0.5 mg; P = 0.1832 M: 4 mg O 1 mg; P = 0.2311 O 2 mg; P = 0.0024 O 3mg; P < 0.0001

M 4 mg vs. Placebo: P = 0.0023

Soergel, et al. 6 No. 30 O: Placebo O vs placebo: 2014 Age 18-50 1.5, 3, 4.5 mg O 3 & 4.5mg (P < .02) 1.5-mg (P < .007)

O v M: 3 mg (P < .02;) 4.5 mg (P < .005)

O: oliceridine M: morphine RESULTS: EFFICACY

Oliceridine vs. placebo: Oliceridine vs morphine: -Most studies reviewed had significant -Most studies reviewed did not have P values, providing evidence for efficacy significant P values, providing evidence for 1,2,3,4,6 against placebo. less efficacy against morphine.6 -Measurements looked at for efficacy -Only one study conducted by Soergel and include responder rates1,3, pain scores2,4, NRS TWA0-48, changes5, and colleagues had significant findings for CPT hand removal latencies.6 oliceridine’s efficacy compared to morphine’s efficacy.1,2,3,4,5 -Only one study conducted by Viscusi and colleagues showed no significance -Although the 3 and 4.5 mg oliceridine in oliceridine’s (low dose) efficacy doses were both proven efficacious against compared to the placebo. morphine, the higher dose was more significant. (O 3 mg: P < .02; O 4.5 mg: P < .005)6 Oliceridine vs morphine: • Most studies showed a tolerable safety profile in regard to adverse effects. • A study conducted by N Singla, HS Minkowitz, and colleagues demonstrated that oliceridine has an acceptable safety/tolerability profile and potentially wider therapeutic window than morphine. • ER Viscusi and colleagues also demonstrated RESULTS: favorable safety and tolerability regarding GI SAFETY and respiratory effects compared to morphine.3 • the supplemental oxygen requirements for the oliceridine 0.1, 0.35, and 0.5 mg groups were significantly less than the morphine 1 mg group (p < 0.01). • GI adverse effects for the oliceridine 0.1, 0.35, and 0.5 mg groups were significantly less than the morphine 1 mg group (p < 0.05). • Several other studies reviewed showed similar results. • Comparisons: • None of the studies reviewed compared oliceridine to non-opioids. • The only other opioid that oliceridine has been compared to from our pool of studies is morphine. • Dosing • Equianalgesic dosing has not yet been defined so RESULTS: comparative doses of oliceridine and morphine LIMITATIONS was inconsistent. • In a study conducted by SD Bergese and colleagues, no control group or comparator group was used. • Most studies looked at efficacy of oliceridine compared to placebo only rather than also looking at oliceridine vs morphine efficacy. CONCLUSION

• Based on currently available literature, oliceridine’s use in clinical practice is limited to patient populations undergoing procedures such as abdominoplasties & bunioectomies or that have painful non-surgical medical conditions. • In addition, most studies conducted have looked only at oliceridine efficacy and safety regarding side effects, but none have looked at reducing abuse potential in humans. • One study by C Zamarripa, SR Edwards, and colleagues demonstrates that TRV130 produces reinforcing and antinociceptive effects that are quantitatively similar to oxycodone, and that a biased-signaling profile does not necessarily reduce abuse potential. 7 • Even though this study was conducted in rats, it could be argued that this effect could be similar in humans. • Do we really need a new IV opioid during an opioid epidemic when we should focus more of our resources on finding more novel non-opioid interventions and therapies? Future studies should evaluate oliceridine compared to other APPLICATIONS available intravenous opioids and TO CLINICAL PRACTICE non-opioids as far as efficacy, safety, dependency, and costs. • 1. 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 • 2. 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 REFERENCES Requiring Parenteral Opioid Therapy. J Pain Res. 2019;12:3113- 3126. Published 2019 Nov 14. doi:10.2147/JPR.S217563 • 3. 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 Mar 11;12:927-943. doi: 10.2147/JPR.S171013. PMID: 30881102; PMCID: PMC6417853. • 4. Singla N, Minkowitz HS, Soergel DG, Burt DA, Subach RA, Salamea MY, Fossler MJ, Skobieranda F. 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 Oct 6;10:2413-2424. doi: 10.2147/JPR.S137952. PMID: 29062240; PMCID: PMC5638571. • 5. 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. REFERENCES 2016;157(1):264-272. doi:10.1097/j.pain.0000000000000363 • 6. Soergel DG, Subach RA, Burnham N, et al. Biased agonism CONTINUED of the μ-opioid receptor by TRV130 increases analgesia and reduces on-target adverse effects versus morphine: A randomized, double-blind, placebo-controlled, crossover study in healthy volunteers. Pain. 2014;155(9):1829-1835. doi:10.1016/j.pain.2014.06.011 • 7. Austin Zamarripa C, Edwards SR, Qureshi HN, Yi JN, Blough BE, Freeman KB. The G-protein biased mu-opioid agonist, TRV130, produces reinforcing and antinociceptive effects that are comparable to oxycodone in rats. Drug Alcohol Depend. 2018;192:158-162. doi:10.1016/j.drugalcdep.2018.08.002