Open-label, rapid initiation pilot study for extended-release buprenorphine subcutaneous injection

Figures & data

Figure 1. Flow diagram outlining procedure used to initiate buprenorphine extended-release in study participants.

COWS, Clinical Opiate Withdrawal Scale; BUP-TM, transmucosal buprenorphine‐containing product; BUP-XR, buprenorphine extended-release injection.

Figure 2. COHORT diagram showing disposition of study participants.

BUP-TM, transmucosal buprenorphine‐containing product; BUP-XR, buprenorphine extended-release injection.

Figure 3. Clinical opiate withdrawal scale (COWS), opioid craving visual analogue scale (OC-VAS) and sedation visual analogue scale (Sedation VAS) scores over time following initiation of buprenorphine extended-release injection (BUP-XR) one hour following an initial dose of 4-mg transmucosal buprenorphine (BUP-TM). Time: D1 is check-in on the day of initiation (Day 1); PTM is prior to administration of BUP-TM; 0 h is prior to BUP-XR injection; D8, D15, D22 and D29 indicate days after buprenorphine injection. Panel A (upper left), COWS Total Score (Mean ± standard deviation [SD]) (Full Analysis Set; n = 24). A score of 0 to 4 is no active withdrawal, 5 to 12 is mild, 13 to 24 is moderate, 25 to 36 is moderately severe, and >36 is severe withdrawal. *p-value ≤0.05 based on t-test for change from PTM value. After injection, COWS scores significantly decreased from a pre-BUP-TM baseline. Panel B (upper right), COWS Total Score (Mean ± SD) by Maximum COWS Severity Subgroup (Full Analysis Set). Subgroups are based on maximum COWS total score: participants whose maximum occurred at the pre-BUP-XR (MAXpre) timepoint and those whose maximum occurred at a post-BUP-XR (MAXpost). Participants with a maximum severity post-BUP-XR injection tended to have a slower decline in withdrawal severity immediately following BUP-XR injection, but COWS scores still returned to the pre-BUP-XR average between 4 to 6 hours post-BUP-XR. Panel C (lower left), OC-VAS Score (Mean ± SD) (Full Analysis Set). *p-value ≤0.05 based on t-test for change from PTM value. A steady decrease from baseline in opioid craving was measured to 48 h post-BUP-XR and was sustained to Day 29 of treatment. Panel D (lower right),” Sedation VAS Score (Mean ± SD) (Safety Analysis Set). *p-value ≤0.05 based on t-test for change from 0 h value. Mean sedation VAS score tended to be highest between 4 to 8 hours post-BUP-XR but did not change substantially up to 36 hours post-BUP-XR.

Table 1. COWS total score normalized AUC through 1, 6, 12, 24 and 48 hours post-BUP-XR 300 mg.

Interval	Through 1 hour Post-BUP-XR (n = 24)	Through 6 hours Post-BUP-XR (n = 23)	Through 12 hours Post-BUP-XR (n = 23)	Through 24 hours Post-BUP-XR (n = 23)	Through 48 hours Post-BUP-XR (n = 23)
COWS Score
Mean (SD)	11.91 (3.700)	9.27 (3.939)	7.91 (3.772)	6.59 (3.021)	5.03 (2.566)
Min, Max	5.0, 20.0	4.2, 21.7	2.0, 18.5	1.0, 14.3	0.8, 11.7

Data are from the full analysis set; COWS, Clinical Opiate Withdrawal Scale; AUC, area under the curve; BUP-XR, buprenorphine extended-release injection, SD, standard deviation.

AUC was normalized by participant for the actual time duration of the interval. The normalized AUC for COWS could be viewed as the averaged COWS over the corresponding time interval. Participants were included in a given interval if they had a pre-BUP-XR COWS assessment and a COWS assessment at the terminal timepoint for the interval.