10 Jul Optimistic Results From Phase 3 Study of RBP-6000 Buprenorphine Monthly Depot for Treatment of Opioid Use Disorder
Medical Research.com Interview with:
Dr. Christian Heidbreder, PhD
Chief Scientific Officer
Richmond, VA 23235, USA
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: This pivotal Phase 3 clinical trial (RB-US-13-0001) evaluated the efficacy and safety of RBP-6000, an investigational once-monthly injectable buprenorphine in the ATRIGEL® delivery system for the treatment of adults with moderate-to-severe opioid use disorder (OUD) as part of a complete treatment plan to include counseling and psychosocial support1.
The 24-week Phase 3 study met its primary and key secondary endpoints, demonstrating statistically significant differences in percentage abstinence and treatment success across both dosage regimens of RBP-6000 versus placebo1.
The findings 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. These outcomes were associated with buprenorphine plasma concentrations ≥ 2 ng/mL and predicted whole brain mu-opioid receptor occupancy of ≥ 70%, and were also maintained for the one-month dosing intervals and for the entire treatment duration1.
The results were confirmed by exposure-response analyses demonstrating a relationship between buprenorphine plasma concentrations, abstinence, withdrawal symptoms and opioid craving1.
RBP-6000 was generally well tolerated and had a safety profile consistent with that of transmucosal buprenorphine. Injection site reactions were not treatment-limiting. The most common (reported in ≥ 5% of subjects) treatment-emergent adverse events (TEAEs) reported in the active total group were constipation, headache, nausea, injection site pruritus, vomiting, increased hepatic enzyme, fatigue and injection site pain1.
MedicalResearch.com: What should clinicians and patients take away from your report?
Response: Opioid use disorder is a chronic medical condition. Medication-assisted treatment (MAT), the use of medications in combination with counseling and/or behavioral therapies, is one approach to the treatment of substance use disorder2. If approved, RBP-6000 could represent a potentially important new option for the treatment of opioid use disorder.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: The medical community should consider pursuing the following types of research:
1) More research on craving. Growing evidence suggests that the ability to regulate craving could serve as a biomarker of treatment-related changes over time. Furthermore, in our Phase 3 trials, craving was the number one predictor of treatment dropout. Future research should also focus on new molecular targets with mechanisms of action involved in craving; these are likely to be useful across addictive disorders.
2) Investment in health economics and outcomes research as part of clinical development plans (prospective HEOR) and post-marketing studies (retrospective and prospective HEOR).
3) Research on how to combine pharmacotherapies with cognitive behavioral therapy and contingency management. Importantly, how could such combinations be implemented in real world settings?
4) More research on risk/vulnerability phenotypes.
5) More collaborative research efforts on the pharmacogenomics of addiction and its challenges including how to characterize/quantify pharmacotherapeutic response (efficacy, nonadherence, treatment duration, concurrent medications use, etc.) and how to define patients’ characteristics (differential diagnosis, illness course, comorbidities, etc.). Same effort on the pharmacogenomics of safety.
6) More translational medicine approaches to support good decision making processes as early as possible in drug development.
MedicalResearch.com: Is there anything else you would like to add?
Response: Despite the growing epidemic of opioid use disorder and its impact on health and productivity, most individuals with this disorder do not receive treatment. It has been estimated that only 29% of patients with a lifetime history of nonmedical prescription opioid use disorder ever sought help or treatment based on 2012-2013 data3; among patients who are treated, the median delay from disease onset to treatment was 3.8 years based on 2004-2005 data4. In 2013 at publicly funded US treatment facilities, only 26.8% of 307,180 admissions for heroin treatment and 18.0% of 147,990 admissions for opioid use disorder treatment involved methadone or buprenorphine as part of the treatment plan5.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
1. Learned S. RBP-6000 buprenorphine monthly depot demonstrates efficacy, safety, and exposure/ response relationship in opioid use disorder. Presented during late-breaking research oral presentations at 79th Annual Scientific Meeting of the College on Problems of Drug Dependence (CPDD) Montreal, Canada, June 17-22, 2017.
2. Substance Abuse and Mental Health Services Administration. 2015. Medication and Counseling Treatment. Retrieved from: https://www.samhsa.gov/medication-assisted-treatment/treatment. Accessed June 28, 2017.
3. Saha, T. et al. Nonmedical Prescription Opioid Use and DSM-5 Nonmedical Prescription Opioid Use Disorder in the United States. J Clin Psychiatry. 2016;77(6):772-780.
4. Blanco, C., Iza, M., Schwartz, R. P., Rafful, C., Wang, S., & Olfson, M. (2013). Probability and predictors of treatment-seeking for prescription opioid use disorders: A National Study. Drug and Alcohol Dependence, 131(0), 143–148. http://doi.org/10.1016/j.drugalcdep.2012.12.013
5. Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality. Treatment Episode Data Set (TEDS): 2003-2013. National Admissions to Substance Abuse Treatment Services. BHSIS Series X-XX, HHS Publication No. (SMA) XX-XXXX. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2015.
Citation: Abstract presented at the 79th Annual Scientific Meeting of the College on Problems of Drug Dependence
Results from the Phase 3 Study of RBP-6000 Buprenorphine Monthly Depot for the Treatment of Opioid Use Disorder
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