Monthly buprenorphine depot RBP-6000 effective, safe for opioid addiction

Indivior recently presented phase 3 findings that indicated efficacy and safety of RBP-6000, an investigational once-monthly injectable buprenorphine in the Atrigel delivery system, for treatment of moderate-to-severe opioid use disorder.

“The clinical data from our phase 3 study also showed that outcomes with RBP-6000 are consistent across other secondary clinical endpoints, including control of craving and withdrawal symptoms, as compared to placebo,” Christian Heidbreder, PhD, chief scientific officer of Indivior, said in a press release. “These outcomes started with the first dose of RBP-6000, which achieved buprenorphine plasma concentrations 2 ng/mL and predicted whole brain µ-opioid receptor occupancy of 70%, and were also maintained for the 1-month dosing intervals and for the entire treatment duration.”

To determine safety and efficacy of RBP-6000 for moderate-to-severe opioid use disorder, researchers conducted a phase 3 study among 504 treatment-seeking adults, aged 19 to 54 years, with moderate or severe opioid use disorder not currently receiving medication-assisted treatment. Study participants were randomly assigned to receive two dosages of RBP-6000 (n = 404) or placebo (n = 100).

Prior to randomization, participants were inducted and dose-stabilized on transmucosal buprenorphine product to suppress opioid withdrawal symptoms and confirm lack of buprenorphine allergy. Suboxone (buprenorphine/naloxone, Indivior) sublingual film was used for induction. Supplemental dosing with any buprenorphine-containing product was not permitted after randomization.

Study participants received six once-monthly 300-mg doses, two once-monthly 300-mg doses followed by four once-monthly 100-mg doses, or six once-monthly subcutaneous injections of placebo for 24 weeks. All participants received manual-guided psychosocial support at least once a week.

Abstinence rates were significantly higher among participants who received 300 mg of RBP-6000 (41.3%) and 300 mg/100 mg of RBP-6000 (42.7%), compared with placebo (5%; P < .0001).

Participants who received 300 mg (29.1%) and 300 mg/100 mg of RBP-6000 (28.4%) were more likely to test negative on at least 80% of urine samples and report negative illicit opioid use, compared with placebo (2%; P < .0001).

Exposure-response analysis indicated a positive relationship between buprenorphine exposure, -opioid receptor occupancy and clinical endpoints of abstinence, withdrawal symptoms and opioid craving.

Serious treatment-emergent adverse events occurred among 2.7% of participants who received RBP-6000, compared with 5% who received placebo.

Severe treatment-emergent adverse events occurred among 6.9% of participants who received RBP-6000, compared with 4% who received placebo.

Discontinuation occurred in 4.9% of participants who received RBP-6000, compared with 2% who received placebo.

The most common treatment-emergent adverse events were headache, constipation, nausea, injection site pruritus, vomiting, insomnia and upper respiratory tract infection.

“Opioid use disorder is a chronic, relapsing medical condition with multiple factors playing a role and impacting patient outcomes, including control of withdrawal symptoms, cravings and relapse to illicit opioid use,” study researcher Amit Vijapura, MD, of Vijapura Behavioral Health LLC, Jacksonville, Florida, said in the release. “If approved, RBP-6000 could help address the unmet needs of patients and represent a potentially important new option for the treatment of opioid use disorder.”

Reference:

Learned S, et al. RBP-6000 buprenorphine monthly depot demonstrates efficacy, safety, and exposure/response relationship in opioid use disorder. Presented at: College on Problems of Drug Dependence Annual Meeting; June 17-22, 2017; Montreal.