Investigational Drug for Opioid Disorder Meets Primary and Secondary Endpoints in Phase 3 Trial

An investigational form of buprenorphine has been found to meet its primary and secondary endpoints in a phase 3 trial.

An investigational, once-monthly, injectable form of buprenorphine (RBP-6000/Indivior) has been found to meet its primary and secondary endpoints in a phase 3 trial studying its effects in the treatment of moderate-to-severe opioid use disorder (OUD) in adult patients. The data was presented in a late-breaking presentation at the 79th Annual Scientific Meeting of the College on Problems of Drug Dependence meeting in Montreal.

“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,” Amit Vijapura, MD, psychiatrist and study principal investigator, said in a news release announcing the results. “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.”

RBP-6000 is an investigational, sustained-release formulation of buprenorphine that uses the Atrigel (Indivior) delivery system. This system consists of a polymeric solution of a biodegradable poly-(DL-lactide-co-glycolide) co-polymer dissolved in N-methyl pyrrolidone (NMP). After subcutaneous injection, NMP diffuses out of the polymer matrix and the polymer precipitates, trapping the drug inside and forming an amorphous solid depot, which releases the drug over a 1-month period by diffusion as the polymer biodegrades.

In the phase 3 study, clinically and statistically significant differences in the percentage of abstinence and treatment success was defined as any subject with ≥80% of urine samples testing negative for opioids, combined with self-reporting for illicit opioid use from week 5 to week 24, compared with placebo.

The study included 504 treatment-seeking adults with moderate-to-severe OUD who were not currently receiving medication-assisted treatment, ranging in age from 19 to 64 years. The patients were randomized to either the investigational drug group (n = 404) or the placebo group (n = 100).

Before randomization, all subjects were inducted and dose-stabilized onto a transmucosal product containing buprenorphine to suppress their opioid withdrawal symptoms and to ensure they were not allergic to the drug. The subjects were considered dose-stabilized when their cravings and withdrawal symptoms were clinically controlled, which was defined as <20 on the 100-point Opioid Craving visual analog scale (VAS), and <12 on a 48-point clinical opiate withdrawal scale (COWS) for a minimum of 24 hours. After randomization, supplemental dosing with any product containing buprenorphine was prohibited.

The randomized subjects then received either 6, in-clinic, once-monthly, 300-mg doses of the study drug (300/300 mg); 2, in-clinic, once-monthly, 300-mg doses followed by 4, in-clinic, once-monthly 100-mg doses of the study drug (300/100 mg); or 6, in-clinic, once-monthly, subcutaneous injections of placebo. All doses in all groups were separated by 28 + 2 days. All subjects were also given individual drug counseling and psychosocial support at least once a week throughout the study.

The primary endpoint was the mean percentage of abstinence from week 5 to week 24 as measured by opioid-free weeks, which was ascertained by the percentage of urine samples that tested negative for opioids, combined with negative self-reports of illicit opioid use. The key secondary endpoint was treatment success as defined by any subject who achieved ≥80% of urine samples testing negative for opioids, combined with negative self-reports of illicit opioid use. The safety of the investigational drug was also assessed, relative to placebo.

The results showed that both primary and secondary endpoints were met. Both dosage regimens of RBP-6000 yielded significantly higher abstinence rates compared with placebo: 300/300 mg, 41.3%; 300/100 mg, 42.7%; and placebo, 5.0% (P < .0001). Both dosage regimens also yielded a higher rate of ≥80% of urine samples testing negative for opioids compared with placebo: 300/300 mg, 29.1%; 300/100 mg, 28.4%; and placebo, 2.0% (P < .0001).

Significantly more subjects in both dosage groups of the investigational drug completed the study compared with those on placebo: 300/300 mg, 64.3%; 300/100 mg, 61.3%; and placebo, 33.3% (P < .0001).

“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,” said Christian Heidbreder, PhD, chief scientific officer of Indivior, said in the news release. “These outcomes started with the first dose of RBP-6000, which achieved buprenorphine plasma concentrations ≥2 ng/mL and predicted whole brain mu-opioid receptor occupancy of ≥70%, and were also maintained for the 1-month dosing intervals and for the entire treatment duration.”

The investigational drug was generally well tolerated. In respect to treatment-emergent adverse events (TEAEs), 2.7% of subjects in both dosage regimens combined experienced a serious TEAE compared with 5.0% of the subjects on placebo; 6.9% of subjects in both dosage regimens combined experienced a severe TEAE compared with 4.0% of subjects on placebo; and 4.2% of subjects in both dosage regimens combined discontinued treatment due to TEAEs compared with 2.0% of subjects on placebo.

The most common TEAEs reported in the combined investigational drug groups were headache, constipation, nausea, injection site pruritus, vomiting, insomnia, and upper respiratory tract infection, reported in ≥5% of subjects. The investigational drug had no unexpected safety findings in this study.

In May, Indivior submitted a New Drug Application to the US Food and Drug Administration to seek marketing approval for RBP-6000 for the treatment of adults with moderate-to-severe OUD as part of a complete treatment plan to include counseling and psychosocial support.