By Megan Brooks
NEW YORK—For adults seeking treatment for opioid use disorder (OUD), weekly or monthly subcutaneous injections of extended-release buprenorphine is noninferior to daily sublingual buprenorphine-naloxone tablets, results of a clinical trial indicate.
"Despite its efficacy, currently approved daily sublingual and buccal buprenorphine formulations have limitations, including suboptimal medication adherence, diversion, intravenous misuse, and unintended pediatric exposures," researchers note in a paper online today in JAMA Internal Medicine.
"Having a long acting injectable buprenorphine depot that can be administered by the health care provider directly to the patient on the first day of treatment without the need for a take-home prescription for buprenorphine provides an opportunity to decrease misuse, abuse and diversion of transmucosal buprenorphine, and potentially to increase adherence and improve treatment outcomes for OUD," first author Dr. Michelle Lofwall from the Center on Drug and Alcohol Research, University of Kentucky, in Lexington, told Reuters Health.
Braeburn Pharmaceuticals is in late-stage development of a subcutaneous buprenorphine formulation, now known as CAM2038, which has fast-track and priority-review designations at the U.S. Food and Drug Administration (FDA).
Dr. Lofwall and colleagues tested CAM2038 in a phase 3 double-blind study of 428 adults (263 men, mean age 38) who were seeking treatment for moderate to severe OUD.
By random allocation, 213 received weekly subcutaneous buprenorphine injections for 12 weeks followed by monthly injections for another 12 weeks (SC-BPN group) and 215 received daily sublingual tablets of buprenorphine/naloxone for 24 weeks (SL-BPN/NX group).
Symptoms of opioid craving and withdrawal, measured on standard scales, were suppressed immediately in both groups from the first day throughout the study period without significant between-group differences.
The proportion of opioid-negative urine samples was 35% and response rate was 17% with SC-BPN compared to 28% and 14%, respectively, with SL-BPN/NX. Patients were considered to have responded to treatment if they showed no evidence of illicit opioid use. Both of these primary outcomes demonstrated noninferiority.
The safety profile of subcutaneous buprenorphine was similar to that of the sublingual formulation, with the exception of some mild to moderate injection-site adverse events, the researchers say.
There were five nonfatal drug overdoses, all in the SL-BPN/NX group. Four were accidental (three involving heroin and one involving clonazepam) and one was intentional (involving doxepin hydrochloride, prazosin hydrochloride, and venlafaxine).
It's noteworthy, the researchers say, that one heroin overdose occurred after a participant was jailed for several days without access to their SL-BPN/NX and, on release, used heroin to self-treat withdrawal symptoms and overdosed.
"These results support the efficacy of long-acting weekly and monthly subcutaneous depot buprenorphine formulations as an additional OUD treatment option. These formulations may also address potential limitations and concerns about daily dosing, including diversion, misuse, and accidental exposure of medication to children," they conclude.
Braeburn Pharmaceuticals supported the study and played a role in its design and conduct, interpretation of the data and preparation and review of the manuscript. Dr. Lofwall and several coauthors disclosed financial relationships with the company.
JAMA Intern Med 2018.
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