Posters

Poster –

Buprenorphine Buccal Film for Chronic Low Back Pain in 2 Double-blind, Placebo-controlled, Randomized Withdrawal Trials:
A Pooled Analysis of Subgroups Based on Baseline Pain Severity

Mancia Ko, PharmD¹; Gary Cutter, PhD^2,3; Todd Kunkel, PharmD¹

¹ BioDelivery Sciences International, Inc., Raleigh, NC, USA; ² Pythagoras, Inc., Birmingham, AL, USA; ³ University of Alabama at Birmingham School of Public Health, Department of Biostatistics, Birmingham, AL, USA

Buprenorphine Buccal Film (BELBUCA®)

• —Buprenorphine is an atypical opioid and a partial µ-opioid receptor agonist, with demonstrated efficacy as an analgesic and favorable safety properties that may provide an improved risk-benefit profile relative to other opioids1
• —As with all Schedule II long-acting opioids, buprenorphine buccal film (BBF) is approved by the US Food and Drug Administration for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate2
• —Two previous phase 3 clinical trials established the efficacy of BBF for treating chronic low back pain in opioid-naive3 and opioid-experienced4 subjects (ClinicalTrials.gov NCT01633944 and NCT01675167, respectively)
• —Both studies used an enriched enrollment, randomized withdrawal design that consisted of an open-label BBF titration phase followed by a randomized, double-blind phase in which subjects either continued treatment with BBF or were switched to placebo3,4 (Figure 1)
• —After 12 weeks of double-blind treatment, mean average daily pain scores worsened significantly less from baseline in subjects who continued use of BBF than in those who switched to placebo3,4
• —Subjects in the BBF group also had significantly lower pain scores at Week 1 and at all subsequent time points through Week 123,4

Objective

—This post hoc analysis pooled data from both aforementioned clinical trials to characterize further the efficacy of BBF on the basis of baseline pain severity

Presentation Slide Handouts: Poster Presentation

DOI: 10-5055-bupe-21-pp-0070

References:

1.Marshall B, et al. Pain Manag. 2019;9(2):131-138.
2.Webster LR, et al. Adv Ther. 2020;37(11):4685-4696.
3.United States Drug Enforcement Administration. Drug scheduling. https://www.dea.gov/drug-scheduling.
4.Belbuca. Package insert. BioDelivery Sciences International, Inc.; 2019.
5.Webster LR, et al. Pain Med. 2016;17(6):1112-1130.
6.Kopecky EA, et al. J Clin Pharmacol. 2017;57(4):500-512.
7.Shram MJ, et al. J Clin Psychopharmacol. 2015;35(3):242-9.

Poster – Pharmacokinetic and Pupillometry Outcomes from a Phase 1 Placebo-controlled Trial
to Compare the Effects of Buprenorphine Buccal Film and Oral Oxycodone Hydrochloride

Lynn Webster, MD¹; Jacqueline Cater, PhD²; Thomas Smith, MD³

¹ Center for U.S. Policy, Salt Lake City, UT, USA; ² ICON plc, Philadelphia, PA, USA; ³ BioDelivery Sciences International, Inc., Raleigh, NC, USA

Background

• —The opioid crisis has led to increased concern about the safety of opioids administered for chronic pain, especially regarding abuse and respiratory depression–associated death1
• —As a partial μ-opioid receptor agonist, buprenorphine has unique properties that distinguish it from full μ-opioid receptor agonists
  • Buprenorphine is classified as a Schedule III drug because it has a lower abuse potential than full µ-opioid receptor agonists2,3
• —Buprenorphine buccal film (BELBUCA®, BBF) is approved by the US Food and Drug Administration for use in patients with pain severe enough to require daily, around-the-clock, long-term opioid treatment and for whom alternative treatment options are inadequate4
• —In this phase 1 study, evaluation of the primary endpoint revealed immediate-release oxycodone administration led to a significant, dose-dependent decrease in respiratory drive, whereas BBF did not (ClinicalTrials.gov Identifier: NCT03996694)
• —The pharmacokinetic and pupillometry outcomes presented here were chosen because of their relevance for respiratory safety and potential risk for abuse
  • The abuse quotient (AQ) is a quantitative measure of pharmacokinetic parameters to compare an aspect of abuse potential across opioids5
  • oPrevious studies have shown a relationship between pupil constriction and “drug liking” in the context of opioid abuse6,7

Purpose

—Here we report secondary outcomes from the aforementioned phase 1 clinical trial, including effects of BBF and immediate-release oral oxycodone on pharmacokinetic, and pupillometry assessments.

Presentation Slide Handouts: Poster Presentation

DOI: 10-5055-bupe-21-pp-0065

References:

1.Marshall B, et al. Pain Manag. 2019;9(2):131-138.
2.Webster LR, et al. Adv Ther. 2020;37(11):4685-4696.
3.United States Drug Enforcement Administration. Drug scheduling. https://www.dea.gov/drug-scheduling.
4.Belbuca. Package insert. BioDelivery Sciences International, Inc.; 2019.
5.Webster LR, et al. Pain Med. 2016;17(6):1112-1130.
6.Kopecky EA, et al. J Clin Pharmacol. 2017;57(4):500-512.
7.Shram MJ, et al. J Clin Psychopharmacol. 2015;35(3):242-9.

Poster – Respiratory Outcomes from a Phase 1, Placebo-controlled Trial to Compare the Effects of Buprenorphine Buccal Film and Oral Oxycodone Hydrochloride

Lynn Webster, MD¹; Jacqueline Cater, PhD²; Thomas Smith, MD³

¹ Center for U.S. Policy, Salt Lake City, UT, USA; ² ICON plc, Philadelphia, PA, USA; ³ BioDelivery Sciences International, Inc., Raleigh, NC, USA

Background

• —Respiratory depression is the leading cause of death due to opioid overdose1
• —Inhibition of respiratory drive (ie, the ability of neuronal respiratory centers to control and regulate ventilation) is a major contributor to respiratory depression2
• —Buprenorphine is a partial µ-opioid receptor agonist that exhibits a ceiling effect for respiratory depression when administered intravenously, unlike full µ-opioid receptor agonists (eg, morphine, oxycodone, fentanyl)3,4
• —Partial agonism only refers to receptor-level activation and not analgesic efficacy, as buprenorphine provides analgesic efficacy comparable to that of full µ-opioid receptor agonists5
• −This partial agonism at the µ-opioid receptor, together with antagonism at the κ and δ opioid receptors and agonism at the nociceptin receptor (formerly known as opioid receptor-like 1 or ORL-1), may play a role in limiting common opioid-related adverse events (AEs) such as respiratory depression

Purpose

—This study compared the effects of buprenorphine buccal film (BBF; BELBUCA®) with the effects of immediate-release oral oxycodone on respiratory outcomes to differentiate impact of a partial µ-opioid receptor agonist (ie, BBF) from that of a full µ-opioid receptor agonist (ie, oxycodone)

Presentation Slide Handouts: Poster Presentation

DOI: 10-5055-bupe-21-pp-0060

References:

1. White JM, Irvine RJ. Addiction. 1999;94(7):961-972.
2.Pattinson KTS. Br J Anaesth. 2008;100(6):747-758. doi:10.1093/bja/aen094
3.Dahan A, et al. Br J Anaesth. 2005;94(6):825-834. doi:10.1093/bja/aei145
4.Dahan A, et al. Br J Anaesth. 2006;96(5):627-632. doi:10.1093/bja/ael051
5.Gudin J, Fudin J. Pain Ther. 2020;9(1):41-54. doi:10.1007/s40122-019-00143-6
6.Hale M, et al. J Pain Res. 2017;10: 233-240. doi:10.2147/JPR.S120170
7.Rauck RL, et al. Postgrad Med. 2016;128(1):1-11. doi:10.1080/00325481.2016.1128307
8.Gimbel J, et al. Pain. 2016;157(11):2517-2526. doi:10.1097/j.pain.0000000000000670