Assessment of potentially abuse-related events in two phase 3 studies of NKTR-181, a novel opioid analgesic, using the MADDERS® system (Misuse, Abuse, and Diversion Drug Event Reporting System)

• Published in: Current medical research and opinion Vol. 35; no. 9; pp. 1513 - 1522
• Main Authors: Lanier, Ryan K., Henningfield, Jack E., Gudin, Jeffrey, Rauck, Richard, Elder, Harrison, Erpelding, Nathalie, Treister, Roi, Gimbel, Joseph, Tagliaferri, Mary, Doberstein, Stephen K., Di Fonzo, Carlo J., Lu, Lin, Siddhanti, Suresh, Katz, Nathaniel P.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02-09-2019
• Subjects: Abuse potential; chronic pain; clinical trial; drug accountability; opioid; opioid abuse; potentially abuse-related events; clinical trial; chronic pain; opioid abuse; drug accountability; opioid; potentially abuse-related events; Abuse potential
• ISSN: 0300-7995; 1473-4877
• DOI: 10.1080/03007995.2019.1594744

Objective: To prospectively evaluate the abuse potential of NKTR-181, a novel opioid analgesic, in two phase 3 clinical trials using a newly developed reporting system: the Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS®).
Methods: SUMMIT-07 was an enriched enrollment randomized withdrawal study that examined the safety and efficacy of NKTR-181 across 12 weeks in opioid-naïve subjects with chronic low back pain. SUMMIT-LTS was a 52 week open-label study in opioid-naïve and experienced subjects with chronic low back pain or noncancer pain rolled over from SUMMIT-07 or enrolled de novo. System evaluations were triggered by adverse events of interest and drug accountability discrepancies signaling potentially abuse-related events. Each event was assigned a primary classification and supplementary classification(s) by investigators and by a blinded, independent committee of substance abuse experts (adjudicators). At the final study visit, investigators administered a survey to subjects to identify overlooked events of interest.
Results: Seventy-nine (6.6%) of 1189 subjects were associated with 86 events in SUMMIT-07 and 51 (8.0%) of 638 subjects were associated with 59 events in SUMMIT-LTS. Most events were attributed to "Withdrawal" and, primarily in SUMMIT-07, "Therapeutic Error" (unintentional overuse) or "Misuse" (intentional overuse for a therapeutic purpose) of study medication. Adjudicators identified five possible "Abuse" events (three NKTR-181, two placebo) in SUMMIT-07 and four possible "Abuse" events (all NKTR-181) in SUMMIT-LTS.
Conclusions: The MADDERS® system discerns potentially abuse-related events and identified low rates of withdrawal and a low risk of abuse potential, diversion or addiction associated with NKTR-181 in phase 3 trials.