Positive results have been reported from a pivotal phase 3 study of RBP-6000 (buprenorphine monthly depot, Indivior PLC), an investigational drug for the treatment of opioid use disorder as part of a complete treatment plan that includes counseling and psychosocial support. If RBP-6000 receives FDA approval within the assumed six-month priority review timeline, a marketing authorization could be granted in the fourth quarter of 2017.
RBP-6000 is an investigational buprenorphine sustained-release formulation using Indivior’s Atrigel delivery system, which consists of a polymeric solution of a biodegradable poly-(DL-lactide-co-glycolide) co-polymer dissolved in N-methyl pyrrolidone (NMP), a water-miscible biocompatible solvent. After subcutaneous (SC) injection, NMP diffuses out of the polymer matrix and the polymer precipitates, trapping the drug inside and forming an amorphous solid depot in situ. The depot releases buprenorphine over a one-month period by diffusion as the polymer biodegrades.
RBP-6000 previously received a fast track designation from the FDA. Fast track status is granted to facilitate and expedite the development and review of drugs that are intended to treat a serious condition and with nonclinical or clinical data that demonstrate the potential to address an unmet medical need.
The pivotal trial was a multicenter, randomized, double-blind, placebo-controlled study involving 489 subjects with moderate or severe opioid use disorder (based on criteria from the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders) who were not currently in treatment but were seeking medication-assisted treatment for opioid use disorder. The subjects were initially treated with Suboxone (buprenorphine/naloxone, Indivior) sublingual film for three days according to the product’s prescribing information to prevent withdrawal from opiates and to ensure the lack of allergy to buprenorphine. The subjects then completed a four- to 11-day Suboxone dose adjustment, with doses ranging from 8 mg to 24 mg.
Once the subjects met the randomization criteria of no significant opioid craving (less than or equal to 20 mm on the Opioid Craving Visual Analog Scale [VAS]) or withdrawal (a score of less than or equal to 12 on the Clinical Opiate Withdrawal Scale [COWS]) after at least seven days of Suboxone sublingual film therapy, they were randomly assigned to receive one of two dosing regimens of RBP-6000 or placebo of the equivalent volume in six SC injections separated by 28 days. Subjects given dose regimen number 1 of RBP-6000 received one injection of 300 mg RBP-6000 on day 1 and then every 28 days thereafter. Subjects given dose regimen number 2 of RBP-6000 received one injection of 300 mg RBP-6000 on day 1 and one on day 29, which were followed by four injections (once every 28 days) of RBP-6000 100 mg.
The study’s primary objective was to assess the efficacy of monthly SC injections of RBP-6000 in two dosing regimens containing either buprenorphine 300 mg for six injections or 300 mg for two injections, followed by buprenorphine 100 mg for four injections, compared with placebo during a six-month dosing period in subjects not currently in treatment but seeking medication-assisted treatment for opioid use disorder.
RBP-6000 achieved the primary endpoint of the cumulative distribution function (CDF) of the percentage of urine samples negative for opioids combined with self-reports negative for illicit opioid use collected from week 5 through week 24 (P < 0.0001 for both dosage regimens versus placebo).
The study’s key secondary endpoint was treatment success, defined as any subject with greater than or equal to 80% of urine samples negative for opioids combined with self-reports negative for illicit opioid use from week 5 through week 24. The secondary endpoint was also achieved for both dosage regimens compared with placebo (P < 0.0001).
Safety findings indicated that 2.8% of the subjects treated with RBP-6000 (both dosage regimens combined) experienced serious treatment-emergent adverse events (TEAEs) compared with 5.1% of the subjects given placebo. Of the subjects receiving RBP-6000 (both dosage regimens combined), 4.6% discontinued treatment because of TEAEs compared with 2.0% of the subjects given placebo.
Source: Indivior; August 17, 2016.