Ryan K Lanier1, Jack E Henningfield2,3, Jeffrey Gudin4, Richard Rauck5, Harrison Elder1, Nathalie Erpelding1, Roi Treister6, Joseph Gimbel7, Mary Tagliaferri8, Stephen K Doberstein8, Carlo J Di Fonzo8, Lin Lu8, Suresh Siddhanti8, Nathaniel P Katz1,9. 1. Analgesic Solutions, Wayland, MA, USA. 2. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 3. Pinney Associates, Bethesda, MD, USA. 4. Pain Management Center, Englewood Hospital and Medical Center, Englewood, NJ, USA. 5. Center for Clinical Research, Carolinas Pain Institute, Winston-Salem, NC, USA. 6. Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel. 7. Arizona Research Center, Phoenix, AZ, USA. 8. Nektar Therapeutics, San Francisco, CA, USA. 9. Tufts University School of Medicine, Boston, MA, USA.
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.
RCT Entities:
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.
Authors: Jeffrey Gudin; Richard Rauck; Charles Argoff; Eva Agaiby; Joseph Gimbel; Nathaniel Katz; Stephen K Doberstein; Mary Tagliaferri; Margit Tagliaferri; Jeffrey Potts; James Wild; Lin Lu; Suresh Siddhanti; Martin Hale; John Markman Journal: Pain Med Date: 2020-11-07 Impact factor: 3.750
Authors: Alex S Lee; Suchi Tiwari; Isabel Bishop; Vartan Matossian; Nicole Romaneschi; Takahiro Miyazaki; Laurie VanderVeen; Jonathan Zalevsky; Kathryn DeFea; Catherine M Cahill; Wendy M Walwyn Journal: Front Pain Res (Lausanne) Date: 2021-08-23
Authors: Jack E Henningfield; Jeffrey Gudin; Richard Rauck; Joseph Gimbel; Mary Tagliaferri; Stephen K Doberstein; Carlo Di Fonzo; Lin Lu; Nathaniel Katz; Suresh Siddhanti; Sidney Schnoll Journal: Pain Med Date: 2020-08-01 Impact factor: 3.750