RBP-7000 is an investigational, subcutaneously administered extended-release treatment for schizophrenia.
Indivior announced positive results from 2 phase 3 trials examining the efficacy, safety and tolerability of RBP-7000 (risperidone in ATRIGEL Delivery System), an investigational, subcutaneously administered, monthly extended-release depot formulation, in adults with schizophrenia.
In the 8-week double-blind study, treatment with RBP-7000 90 mg or 120 mg significantly reduced Positive and Negative Syndrome Scale (PANSS) total score and greatly increased the percentage of participants achieving treatment response versus placebo.
“These trials were designed not to require a loading dose or supplemental dosing,” Jay Graham, PharmD, medicines development leader, senior director, Indivior, told MD Magazine. “We are leveraging a known compound, with known efficacy, known safety profile in a different dosage form that’s administered monthly.”
In the double-blind study, 354 patients with a DSM-IV-TR diagnosis of schizophrenia were randomized to receive monthly injections of either placebo (n = 119), RBP-7000 90 mg (n = 116) or RBP-7000 120 mg (n = 119), and must have experienced an acute exacerbation of schizophrenia within 8 weeks of screening and been considered likely to benefit from psychiatric hospitalization, and were required to have a PANSS total score between 80—120 at screening, and a score >4 on at least 2 of the following items: hallucinatory behavior, delusions, conceptual disorganization or suspiciousness/persecution.
In the 52-week open-label, outpatient study, some of those who completed the double-blind trial (n = 92), as well as 408 de novo participants with a DSM-IV-TR diagnosis of schizophrenia were enrolled.
Rollover patients were eligible to enroll, regardless of PANSS score at the end of the double-blind study. Stable de novo patients with a DSM-IV-TR diagnosis of schizophrenia and a PANSS total score ≤70 were eligible to participate. Additionally, rollover patients who received 2 injections of placebo or RBP-7000 (90 mg or 120 mg) in the double-blind study, received 11 additional monthly injections of RBP-7000 120 mg in the open-label study.
In the double-blind study, treatment with either RBP-7000 mg or 120 mg significantly reduced PANSS total scores from baseline to day 57—primary endpoint— and as at each post-baseline visit, versus placebo. In the open label study, a decreasing trend in the PANSS total scores was observed from baseline to end of treatment among rollover patients, which suggests continued improvement in acute schizophrenia following months of RBP-7000 exposure.
Among de novo patients, PANSS total scores remained stable throughout. Overall, 72% of double-blind participants and 73% of open-label participants had a ≥1 treatment adverse effect with 1% and 12% of these leading to study discontinuation, respectively.
In the double-blind study, a higher proportion of participants receiving RBP-7000 120 mg (77.8%) reported ≥1 treatment adverse effects versus those receiving RBP-7000 90 mg (70.4%) of placebo (68.6%). A majority of treatment adverse effects were considered mild or moderate in severity.
Serious treatment adverse effects were reported in 1% of double-blind participants and 7% of open label participants, however, none of the 4 deaths in either study were considered related to the study drug. The most common treatment adverse effects reported in the double-blind injection were site pain (19%), headache (19%) and weight increase (10%), while in the open-label study, the most common effects were injection site pain (13%), weight increased (13%) and schizophrenia (8%).
Graham noted that the efficacy profile and the safety profile is similar the safety profile of risperidone. Rollover study participants continuing into the long-term, open-label trial showed continuous improvement in the PANSS total scores during 52 weeks of treatment.
RBP-7000 was designed to optimize dopamine D2 receptor occupancy and achieve rapid therapeutic concentrations without the need for supplemental oral dosing.
It is anticipated that the FDA will make a decision sometime in July.