Why carry out this study?
|
Respiratory depression is a leading cause of death due to opioid overdose and is a serious public health concern. We tested the effect of buprenorphine buccal film compared with oxycodone to distinguish the impact of a partial versus a full μ-opioid receptor agonist on respiratory drive |
What was learned from the study?
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Buprenorphine buccal film did not significantly reduce respiratory drive at any dose compared with placebo |
Administration of oxycodone resulted in a significant dose-dependent decrease in respiratory drive |
Buprenorphine buccal film may be a safer treatment option than full μ-opioid receptor agonists for patients with chronic pain |
Introduction
Purpose
Methods
Subjects
Study Design
Study Schedule and Procedures
Dose Selection
Ventilatory Response to Hypercapnia
Safety
Statistical Analyses
Ethics
Results
Treatment Effect on Minute Ventilation
Test | References (mg) | Least squares mean difference (test − reference) | ||||||
---|---|---|---|---|---|---|---|---|
Estimate | Standard error | Degrees of freedom | t | 95% CI | P value | Effect sizea | ||
Oxycodone 30 mg | Placebo | − 0.79 | 1.96 | 65 | − 0.40 | (− 4.72, 3.13) | 0.687 | 0.10 |
Oxycodone 60 mg | Placebo | − 5.23 | 1.96 | 65 | − 2.66 | (− 9.15, − 1.31) | 0.010 | 0.69 |
BBF 300 µg | Placebo | 1.24 | 1.96 | 65 | 0.63 | (− 2.67, 5.15) | 0.529 | 0.16 |
BBF 600 µg | Placebo | 0.23 | 1.96 | 65 | 0.12 | (− 3.70, 4.15) | 0.908 | 0.03 |
BBF 900 µg | Placebo | 0.93 | 1.96 | 65 | 0.47 | (− 2.99, 4.85) | 0.637 | 0.12 |
BBF 300 µg | Oxycodone 30 | 2.03 | 1.96 | 65 | 1.04 | (− 1.89, 5.96) | 0.304 | 0.27 |
BBF 300 µg | Oxycodone 60 | 6.47 | 1.96 | 65 | 3.29 | (2.55, 10.39) | 0.002 | 0.85 |
BBF 600 µg | Oxycodone 30 | 1.02 | 1.96 | 65 | 0.52 | (− 2.89, 4.94) | 0.604 | 0.13 |
BBF 600 µg | Oxycodone 60 | 5.46 | 1.96 | 65 | 2.78 | (1.53, 9.38) | 0.007 | 0.72 |
BBF 900 µg | Oxycodone 30 | 1.73 | 1.96 | 65 | 0.88 | (− 2.20, 5.65) | 0.383 | 0.23 |
BBF 900 µg | Oxycodone 60 | 6.16 | 1.96 | 65 | 3.14 | (2.25, 10.07) | 0.003 | 0.81 |
Safety
BBF 300 µg (N = 15) N (%) | BBF 600 µg (N = 17) N (%) | BBF 900 µg (N = 17) N (%) | Oxy 30 mg (N = 15) N (%) | Oxy 60 mg (N = 16) N (%) | Placebo (N = 16) N (%) | |
---|---|---|---|---|---|---|
Number of TEAEs | 10 | 28 | 30 | 19 | 45 | 2 |
Subjects with at least one TEAE | 8 (53.3) | 12 (70.6) | 12 (70.6) | 9 (60.0) | 14 (87.5) | 2 (12.5) |
Discontinuation due to an AE | 0 | 1 (5.9) | 0 | 0 | 0 | 0 |
Most common TEAEsa | ||||||
Gastrointestinal disorders | ||||||
Nausea | 0 | 4 (23.5) | 4 (23.5) | 2 (13.3) | 5 (31.3) | 0 |
Vomiting | 1 (6.7) | 1 (5.9) | 4 (23.5) | 2 (13.3) | 6 (37.5) | 0 |
Nervous system disorders and psychiatric disorders | ||||||
Somnolence | 0 | 4 (23.5) | 4 (23.5) | 3 (20.0) | 7 (43.8) | 1 (6.3) |
Euphoric mood | 3 (20.0) | 3 (17.6) | 4 (23.5) | 4 (26.7) | 4 (25.0) | 0 |
Dizziness | 1 (6.7) | 4 (23.5) | 2 (11.8) | 1 (6.7) | 2 (12.5) | 0 |
Headache | 2 (13.3) | 1 (5.9) | 1 (5.9) | 0 | 1 (6.3) | 0 |
Irritability | 0 | 1 (5.9) | 1 (5.9) | 0 | 0 | 0 |
Skin and subcutaneous tissue disorders | ||||||
Pruritus | 0 | 1 (5.9) | 4 (23.5) | 4 (26.7) | 9 (56.3) | 0 |
Hyperhidrosis | 1 (6.7) | 1 (5.9) | 0 | 0 | 2 (12.5) | 1 (6.3) |