Dosing to Effect With Weekly and Monthly Subcutaneous and Daily Sublingual Buprenorphine: Post Hoc Analysis of a Phase 3 Clinical Trial.

Objectives: CAM2038 weekly and monthly extended-release buprenorphine (BPN) formulations are effective for treating opioid use disorder (OUD). Little is known about the effect of dose on patient outcomes, particularly under blinded and flexible dosing conditions. We evaluated the number of dose changes and the impact of (1) dose on treatment outcomes and (2) baseline primary opioid use (heroin vs prescription opioids) and route of use (injection or not) on the dose.

Methods: This was a post hoc analysis of an outpatient randomized double-blind, double-dummy trial comparing weekly (first 12 wk) and monthly (second 12 wk) CAM2038 to SL-BPN (24 wk) for OUD treatment. Dosing was flexible and guided by clinical response. Maximum doses were 32 mg weekly/160 mg monthly CAM2038 and 24 mg/32 mg SL-BPN in the first and second 12 weeks, respectively. Effect of each dose was evaluated using four outcomes: urine drug test (UDT) opioid results, Clinical Opiate Withdrawal Scale scores, Subjective Opiate Withdrawal Scale scores, and need- and desire-to-use opioid visual analogue scales. Associations between baseline route of use and primary opioid used and study dose were investigated.

Results: After titration to 16 mg SL-BPN/24 mg weekly CAM2038, most participants had 0-1 dose adjustments in both first and second 12 weeks. All doses were utilized. Number of adjustments was not associated with retention. Withdrawal, craving, and opioid-positive UDTs decreased for all CAM2038 and SL-BPN doses. There were few clinically significant associations between dose and primary opioid used/route of use.

Conclusions: Results support current practice guidelines, emphasizing the importance of individualized dosing based on patient response.