Low-dose naloxone provides an abuse-deterrent effect to buprenorphine

Figures & data

Figure 1 BBN with the BEMA^® technology.

Notes: BBN is an oral transmucosal dosage form of BN that uses the BEMA^® technology to optimize drug absorption and enhance patient convenience. The film adheres to the inside of the cheek within seconds, and the buprenorphine is efficiently absorbed. The backing layer creates a barrier to facilitate one-way absorption into the cheek. There is no need for patients to avoid talking or swallowing during administration, and the film completely dissolves.
Abbreviations: BBN, BN buccal film; BN, buprenorphine–naloxone; BEMA^®, BioErodible MucoAdhesive.

Table 1 Randomization of study treatments

Treatment day	Treatment sequence
	1	2	3	4
1	A	D	B	C
2	B	A	C	D
3	C	B	D	A
4	D	C	A	B

Notes: A, buprenorphine 0.75 mg; B, buprenorphine 0.75 mg + naloxone 0.1 mg; C, buprenorphine 0.75 mg + naloxone 0.2 mg; D, placebo.

Table 2 Key study events during the treatment phase

Study day	Key study events
0	Entered facility, fasted at midnight
1	Study treatment at 8 am with serial safety/efficacy measurements following for 24 hours
2	Last serial safety/efficacy at approximately 8 am, then observed
3	Observed, fasted at midnight
4	Study treatment at 8 am with serial safety/efficacy measurements following for 24 hours
5	Last safety/efficacy at approximately 8 am, then released from facility
6	Entered facility, fasted at midnight
7	Study treatment at 8 am with serial safety/efficacy measurements following for 24 hours
8	Last serial safety/efficacy at approximately 8 am, then observed
9	Observed, fasted at midnight
10	Study treatment at 8 am with serial safety/efficacy measurements following for 24 hours
11	Last safety/efficacy at approximately 8 am, then released from facility

Table 3 Demographics

Variable	Value
Age (years)a	49.5 (10.5)
Sex, n (%)
Female	6 (40)
Male	9 (60)
Race, n (%)
Caucasian	15 (100.0)
Weight (kg)a	89.6 (18.8)
Height (cm)a	172.6 (9.5)
BMI (kg/m^2)a	30.4 (6.9)
Medical history (%)
Gastrointestinal	93
Nervous system	93
Musculoskeletal	87
Psychiatric	87
Immune	67
Respiratory	67

Note:

a Mean (SD).

Abbreviations: BMI, body mass index; SD, standard deviation.

Figure 2 Subjects requiring rescue medication.

Note: Includes 15-minute scores for subjects who did not rescue.
Abbreviation: BN, buprenorphine–naloxone.

Table 4 COWS total scores

Score, median (min, max)	Buprenorphine (N=15)	BN 0.1 mg (N=15)	BN 0.2 mg (N=15)	Placebo (N=15)
Predose	0.0 (0, 1)	0.0 (0, 2)	0.0 (0, 1)	0.0 (0, 2)
15-minute postdosea	6.0 (0, 18)	14.0 (0, 27)	16.0 (1, 26)	1.0 (0, 23)
Change from predose	6.0 (0, 18)*	14.0 (−1, 26)*,**	16.0 (1, 26)*,**	0.0 (−2, 23)

Notes:

a Or the score obtained immediately prior to rescue treatment;

* P<0.001 vs placebo;

** P<0.001 vs buprenorphine alone.

Abbreviations: COWS, Clinical Opioid Withdrawal Scale; BN, buprenorphine–naloxone.

Table 5 Adverse events by MedDRA body system

Disorders	Buprenorphine (N=15)	BN 0.1 mg (N=15)	BN 0.2 mg (N=15)	Placebo (N=15)
General	4 (26.7)	8 (53.3)	11 (73.7)	3 (30.3)
Nervous system	5 (33.3)	4 (26.7)	6 (40.0)	9 (60.0)
Psychiatric system	6 (40.0)	3 (30.3)	3 (30.3)	0
Musculoskeletal/connective tissue	0	3 (30.3)	3 (30.3)	0
Skin and subcutaneous tissue	1 (6.7)	1 (6.7)	3 (30.3)	0
Vascular	1 (6.7)	1 (6.7)	0	1 (6.7)
Cardiac	0	0	1 (6.7)	0
Eye	0	1 (6.7)	0	0
Infections and infestations	1 (6.7)	0	0	0
Reproductive system and breast	0	1 (6.7)	0	0
Respiratory, thoracic, and mediastinal	0	0	1 (6.7)	0

Note: Data is presented as n (%).

Abbreviations: MedDRA, Medical Dictionary for Regulatory Affairs; BN, buprenorphine–naloxone.