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W9

FIRST DOSE TREATMENT EFFECTS WITH INJECTABLE WEEKLY AND MONTHLY BUPRENORPHINE (CAM2038) AND THE RELATIONSHIP BETWEEN BUPRENORPHINE PLASMA CONCENTRATIONS AND WITHDRAWAL SUPPRESSION IN PARTICIPANTS WITH OPIOID USE DISORDER

Michael P. Frost — Edward V. Nunes2, Michelle R. Lofwall3, Sharon L. Walsh3, Genie L. Bailey4, Brian J. Dawson5, Natalie R. Budilovsky-Kelley6, Adam Friedman6, Carrie Kaempfer6, Joshua M. Cohen6 1The Frost Medical Group, LLC, 2Columbia University Irving Medical Center, New York State Psychiatric Institute, 3University of Kentucky College of Medicine, Center on Drug and Alcohol Research, 4Brown University and Stanley Street Treatment and Resources (SSTAR), 5Ideal Option, 6Braeburn Inc, Plymouth Meeting

2026 ASCP Annual Meeting

Introduction

Early research examining the relationship between buprenorphine plasma concentrations and opioid withdrawal in patients with opioid use disorder (OUD) reported an association between higher plasma concentrations and withdrawal suppression and suggested that plasma concentrations of 0.7 to 1.0 ng/mL were needed to control withdrawal (Kuhlman et al 1998; Greenwald et al 2007). More recent research, however, indicates that withdrawal is effectively suppressed in most patients at lower plasma concentrations (Laffont et al 2022; Walsh et al 2024). CAM2038 is a weekly and monthly injectable buprenorphine medication approved for the treatment of moderate-to-severe OUD and, in clinical studies, has demonstrated withdrawal suppression and reductions in illicit opioid use.

Methods

An open-label, single-dose, pharmacokinetic (PK) study evaluated participants with moderate-to-severe OUD randomized to either CAM2038 32 mg weekly or 128 mg monthly. During the 2-week period preceding CAM2038 administration (Day -13 to Day 1), participants were assessed for self-reported illicit drug use using timeline follow back (TLFB). Prior to CAM2038 administration on Day 1, Clinical Opiate Withdrawal Scale (COWS) scores (mild = 5–12; moderate = 13–24; moderately severe = 25–36; severe = > 36) were also collected. Following CAM2038 administration, participants remained inpatient for 5 days (Day 2 to Day 6) and returned for outpatient visits at Day 8 (last visit for CAM2038 weekly group), Day 15, Day 22, and Day 29. PK samples and COWS scores were collected each inpatient day and at subsequent outpatient visits. Illicit drug use was assessed using TLFB at each outpatient visit. A post-hoc analysis (N=110) evaluated the effect of single-dose CAM2038 32 mg weekly and 128 mg monthly on opioid withdrawal and self-reported illicit drug use throughout the dosing interval and the association between buprenorphine plasma concentrations and withdrawal suppression (defined as COWS < 5).

Results

The mean baseline COWS score on Day 1 was 13 (no participants with COWS scores < 5), which declined to 5 and 7 (53% and 32% with COWS scores < 5) by Day 2 and to 3 and 5 (68% and 61% with COWS scores < 5) by Day 3 in the CAM2038 weekly and monthly groups, respectively. At the end of the weekly and monthly dosing intervals (Day 8 and Day 29), the CAM2038 32 mg weekly group had a mean COWS score of 2 (91% with COWS score < 5) and the CAM2038 128 mg monthly group had a mean COWS score of 1 (95% with COWS score < 5). Among PK samples collected with buprenorphine plasma concentrations < 0.5 ng/mL, 92% co-occurred with COWS scores < 5. No meaningful association was found between plasma concentrations and withdrawal suppression across study time points. Prior to CAM2038 administration, 94% of participants reported use of illicit opioids. When reassessed at the end of the weekly and monthly dosing intervals (Day 8 and Day 29), self-reported illicit opioid use had declined to 14% in the CAM2038 32 mg weekly group and to 18% in the CAM2038 128 mg monthly group. Self-reported use of other illicit drugs was also found to decrease following administration of weekly and monthly CAM2038.

Conclusions

Rapid and sustained withdrawal suppression was observed in participants with OUD treated with weekly and monthly CAM2038. COWS scores < 5 were consistently recorded in participants with the lowest observed buprenorphine plasma concentrations. Rates of selfreported illicit opioid use substantially declined across weekly and monthly dosing intervals. These findings reinforce known treatment effects of weekly and monthly CAM2038 and indicate that very low buprenorphine plasma concentrations (< 0.5 ng/mL) effectively suppress withdrawal.