Buprenorphine Buccal Film for Chronic Pain Management

Figures & data

Table 1. Comparison of the buprenorphine transdermal system and buprenorphine buccal film.

	Buprenorphine transdermal system	Buprenorphine buccal film
Bioavailability	∼15%	46–65%
Doses available in the USA	5, 7.5, 10, 15 and 20 μg/h	75, 150, 300, 450, 600, 750 and 900 μg
Safety
Most common adverse events reported by ≥5% of patients	Nausea, headache, application site pruritus, dizziness, constipation, somnolence, vomiting, application site erythema, dry mouth and application site rash	Nausea, constipation, headache, vomiting, fatigue, dizziness, somnolence, diarrhea, dry mouth and upper respiratory tract infection
Most common adverse events leading to discontinuation in clinical studies	Nausea, dizziness, vomiting, headache and somnolence	Nausea, vomiting and liver function test abnormality
Tolerability	Well tolerated	Well tolerated
Efficacy, opioid-naive trial data/opioid-experienced trial data
≥30% response rates	53%/49%	62%/64%
≥50% response rates	43%/35%	41%/40%
Average cost per month, lowest to highest available dosage strengths in the USA	$313–$817	$352–$857

Figure 1. Buprenorphine buccal film.

Buprenorphine buccal film is a small, bilayered dissolving polymer film that adheres to the buccal mucosa using BioErodible MucoAdhesive^® technology, which enhances bioavailability compared with other routes of administration [59]. Buprenorphine buccal film is available in 75, 150, 300, 450, 600, 750 and 900 μg dosage strengths and facilitates a unidirectional flow of the drug that is approximately 46–65% bioavailable and reaches steady-state levels in approximately 3 days [50,54].

Figure 2. Design of buprenorphine buccal film clinical trials in patients with chronic low back pain.

The safety and efficacy of buprenorphine buccal film were studied in two double-blind, Phase III, randomized, placebo-controlled trials in (A) opioid-experienced [44] and (B) opioid-naive [46] patients that comprised a 2-week screening phase; an open-label titration phase; a 12-week double-blind, placebo-controlled treatment phase; and follow-up. An analgesic taper phase was also included for opioid-experienced patients. (C) The long-term study [45] included rollover patients from (A & B) or de novo recruits and was comprised of a dose-titration period of ≤6 weeks with buprenorphine buccal film; patients who achieved and maintained an optimal dose (300–900 μg/12 h) for ≥7 days continued treatment for a long-term period up to 48 weeks.

Figure 3. Double-blind studies: buprenorphine buccal film significantly reduced pain intensity scores compared with placebo in patients with chronic low back pain.

Primary sensitivity analyses comparing the change from baseline to week 12 in numerical rating scale pain intensity scores in patients receiving placebo compared with those receiving buprenorphine buccal film.

LCL: Lower confidence limit; UCL: Upper confidence limit.

Data taken from [44,46].

Figure 4. Proportion of responders in the double-blind studies.

The percentage of patients achieving ≥30% (A) or ≥50% (B) pain reduction from the period before the open-label titration to week 12 of the double-blind treatment phase.

Table 2. Adverse events occurring in ≥5% of patients receiving buprenorphine buccal film during open-label titration in at least one study.

Adverse event, n (%)	Opioid experienced (n = 810)	Opioid naive (n = 749)	Long-term (n = 506)
Gastrointestinal disorders
Nausea	136 (16.8)	373 (49.8)	52 (10.3)
Constipation	67 (8.3)	97 (13.0)	30 (5.9)
Vomiting	54 (6.7)	58 (7.7)	12 (2.4)
Nervous system disorders
Headache	54 (6.7)	60 (8.0)	18 (3.6)
Dizziness	42 (5.2)	48 (6.4)	None reported
Somnolence	41 (5.1)	52 (6.9)	None reported

Table 3. Adverse events occurring in ≥5% of patients receiving buprenorphine buccal film during the double-blind or long-term treatment studies.

Adverse event, n (%)	Double-blind				Long-term (n = 435)
	Opioid experienced (n = 510)		Opioid naive (n = 461)		Buprenorphine buccal film (n = 435)
	Placebo (n = 256)	Buprenorphine buccal film (n = 254)	Placebo (n = 232)	Buprenorphine buccal film (n = 229)
Gastrointestinal disorders
Nausea	19 (7.4)	19 (7.5)	17 (7.3)	23 (10.0)	36 (8.3)
Vomiting	6 (2.3)	14 (5.5)	1 (0.4)	9 (3.9)	22 (5.1)

Table 4. Response rates across similar studies of opioids.

Chronic pain treatment	Response rate
	≥30%	≥50%
Buprenorphine buccal film	64	40
Hydromorphone (extended release)	61	42
Hydrocodone (extended release)	68	48
Oxymorphone (extended release)	60	48

Values are listed as percent responders [44,66–68].

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