Dataset Information

A Phase I Placebo-Controlled Trial Comparing the Effects of Buprenorphine Buccal Film and Oral Oxycodone Hydrochloride Administration on Respiratory Drive.

ABSTRACT:

Introduction

Buprenorphine is a partial ?-opioid receptor agonist that, unlike full ?-opioid receptor agonists, has been shown to have a ceiling effect on respiratory depression. Buprenorphine buccal film (BBF) is approved by the US Food and Drug Administration for use in patients with chronic pain severe enough to require daily, around-the-clock, long-term opioid treatment and for whom alternative treatment options are inadequate. This study was conducted to compare the effects of BBF and immediate-release oral oxycodone hydrochloride administration on respiratory drive, as measured by the ventilatory response to hypercapnia (VRH) after drug administration.

Methods

Subjects (N?=?19) were men and women, ages 27-41 years, self-identifying as recreational opioid users who were not physically dependent on opioids as determined via a Naloxone Challenge Test. Respiratory drive was evaluated by measuring VRH through the assessment of the maximum decrease in minute ventilation (E_max) after administration of each treatment. The treatments utilized in this study included 300, 600, and 900 ?g BBF; 30 and 60 mg orally administered oxycodone; and placebo (each separated by a 7-day washout period). Effects on respiratory drive were assessed using a double-blind, double-dummy, six-treatment, six-period, placebo-controlled, randomized crossover design. Statistical analyses were performed using a linear mixed-effects model.

Results

The least squares mean differences in minute volume E_max (L/min, versus placebo) were as follows: 300 ?g BBF (+?1.24, P?=?0.529), 600 ?g BBF (+?0.23, P?=?0.908), 900 ?g BBF (+?0.93, P?=?0.637), 30 mg oxycodone (-?0.79, P?=?0.687), and 60 mg oxycodone (-?5.23, P?=?0.010).

Conclusions

BBF did not significantly reduce respiratory drive at any dose compared with placebo, including at the maximum available prescription dose of 900 ?g. Administration of oxycodone resulted in a significant dose-dependent decrease in respiratory drive. These data suggest that BBF may be a safer treatment option than full ?-opioid receptor agonists for patients with chronic pain.

Trial registration

ClinicalTrials.gov identifier, NCT03996694.

SUBMITTER: Webster LR

PROVIDER: S-EPMC7547962 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

A Phase I Placebo-Controlled Trial Comparing the Effects of Buprenorphine Buccal Film and Oral Oxycodone Hydrochloride Administration on Respiratory Drive.

Webster Lynn R LR Hansen Erik E Cater Jacqueline J Smith Thomas T

Advances in therapy 20200925 11

<h4>Introduction</h4>Buprenorphine is a partial μ-opioid receptor agonist that, unlike full μ-opioid receptor agonists, has been shown to have a ceiling effect on respiratory depression. Buprenorphine buccal film (BBF) is approved by the US Food and Drug Administration for use in patients with chronic pain severe enough to require daily, around-the-clock, long-term opioid treatment and for whom alternative treatment options are inadequate. This study was conducted to compare the effects of BBF a ...[more]

PMID: 32978722

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Dataset Information

A Phase I Placebo-Controlled Trial Comparing the Effects of Buprenorphine Buccal Film and Oral Oxycodone Hydrochloride Administration on Respiratory Drive.

Introduction

Methods

Results

Conclusions

Trial registration

Publications

A Phase I Placebo-Controlled Trial Comparing the Effects of Buprenorphine Buccal Film and Oral Oxycodone Hydrochloride Administration on Respiratory Drive.

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