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). (2nd September 2019)

• Record Type: Journal Article
• 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.
• Is Part Of: Current medical research and opinion. Volume 35:Number 9(2019)
• Page Start: 1513
• Page End: 1522
• Publication Date: 2019-09-02
• Subjects: Abuse potential -- potentially abuse-related events -- chronic pain -- clinical trial -- drug accountability -- opioid -- opioid abuse; Clinical medicine -- Periodicals; Therapeutics -- Periodicals; 615.5
• DOI: 10.1080/03007995.2019.1594744
• Languages: English
• ISSNs: 0300-7995

Abstract

Abstract: 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.