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Measuring Opioid Withdrawal in a Phase 3 Study of a New Analgesic, NKTR-181 (Oxycodegol), in Patients with Moderate to Severe Chronic Low Back Pain.

ABSTRACT: OBJECTIVE:To evaluate the SUMMIT-07 trial opioid withdrawal results of NKTR-181 (oxycodegol), a new molecular entity mu-opioid receptor agonist. DESIGN:Phase 3, enriched-enrollment, double-blind, randomized-withdrawal study in patients with chronic low back pain (CLBP). SETTING:Conducted in the United States at multiple sites. METHODS:SUMMIT-07 was comprised of five periods: screening; NKTR-181 open-label titration (100 to 400?mg twice daily); 12-week randomized, double-blind study drug (NKTR-181 or placebo); one-week study drug taper; and two-week safety follow-up. Permitted rescue medication included hydrocodone 5?mg/acetaminophen 300?mg (two tablets daily) for two weeks after randomization, then acetaminophen 1.0?gm daily for the remainder of the trial. Signs and symptoms of drug withdrawal were evaluated using the Clinical Opiate Withdrawal Scale (COWS); Subjective Opiate Withdrawal Scale (SOWS); Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS); and withdrawal-related adverse events. RESULTS:Of 1,190 patients entering titration, one patient had moderate withdrawal (COWS score 13/48 maximum) three days after discontinuing NKTR-181. Of 610 patients randomized (N?=?309, NKTR-181; N?=?301, placebo), no COWS scores indicating withdrawal at a moderate level or greater (i.e., score ?13) were observed at any time point. At day 8 after randomization, week 12, and the end of tapering, COWS scores indicating mild withdrawal (<13) were observed in seven (2.4%), one (0.4%), and one (0.5%) placebo patients, respectively, and three (1.0%), one (0.4%), and five (2.3%) NKTR-181 patients, respectively. Mean SOWS scores in both arms were ?2.8 of 64 possible points at all time points. During the randomized period, of 35 events identified by MADDERS, adjudicators identified 20 possible "withdrawal" events (9 [2.9%] NKTR-181 and 11 [3.7%] placebo). CONCLUSIONS:NKTR-181 exhibited a low rate and severity of opioid withdrawal in SUMMIT-07 patients with CLBP.

SUBMITTER: Henningfield JE

PROVIDER: S-EPMC7530570 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Measuring Opioid Withdrawal in a Phase 3 Study of a New Analgesic, NKTR-181 (Oxycodegol), in Patients with Moderate to Severe Chronic Low Back Pain.

Henningfield Jack E JE Gudin Jeffrey J Rauck Richard R Gimbel Joseph J Tagliaferri Mary M Doberstein Stephen K SK Di Fonzo Carlo C Lu Lin L Katz Nathaniel N Siddhanti Suresh S Schnoll Sidney S

Pain medicine (Malden, Mass.) 20200801 8

<h4>Objective</h4>To evaluate the SUMMIT-07 trial opioid withdrawal results of NKTR-181 (oxycodegol), a new molecular entity mu-opioid receptor agonist.<h4>Design</h4>Phase 3, enriched-enrollment, double-blind, randomized-withdrawal study in patients with chronic low back pain (CLBP).<h4>Setting</h4>Conducted in the United States at multiple sites.<h4>Methods</h4>SUMMIT-07 was comprised of five periods: screening; NKTR-181 open-label titration (100 to 400 mg twice daily); 12-week randomized, dou ...[more]

PMID: 32150255

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Project description:ObjectivesThis post hoc analysis of data from a randomized, double-blind, placebo-controlled, enriched-enrollment randomized-withdrawal Phase III study evaluated the safety, tolerability, and analgesic efficacy of Oxycodone DETERx extended-release (ER), abuse-deterrent capsules (Xtampza® ER) in subjects with chronic low back pain who were successfully transitioned from immediate-release (IR) oxycodone.MethodsContinuous outcomes were analyzed using a mixed-model repeated-measures approach; binomial outcomes were analyzed using chi-squared; and time-to-event outcomes using Kaplan-Meier analyses.ResultsA total of 110 subjects previously prescribed IR oxycodone entered the Open-label Titration Phase. Forty-four subjects were randomized to Oxycodone DETERx (n=22) or placebo (n=22) in the 12-week Double-blind Maintenance Phase. Efficacy results in this subgroup showed a statistically significant difference between Oxycodone DETERx and placebo in average pain intensity scores from Randomization Baseline to Week 12 (least squares mean [± standard error], -1.88 [0.70]; P=0.0078). Additional efficacy results indicated that Oxycodone DETERx vs placebo was associated with a statistically significant benefit in durability of effect from Week 2 through Week 12 (P<0.01), numbers of subjects with a ≥30% (n [%] 10 [45.5%] vs 0 [0%]; P=0.0004) and ≥50% (10 [45.5%] vs 0 [0%]; P=0.0004) improvement in pain intensity, longer time-to-exit (P=0.0014), a greater number of subjects who completed the study (14 [63.6%] vs 4 [18.2%]), and less rescue medication use (acetaminophen; mean [SD], 163.5 [337.8] mg) vs 216.2 [377.3] mg). Adverse event profiles were consistent with opioid class effects and results from the original study; Oxycodone DETERx was well tolerated in subjects previously treated with short-acting oxycodone.ConclusionsOxycodone DETERx resulted in clinically meaningful and statistically significant efficacy in subjects with chronic low back pain who were previously prescribed IR oxycodone and were successfully switched to ER Oxycodone DETERx.

Dataset Information

Measuring Opioid Withdrawal in a Phase 3 Study of a New Analgesic, NKTR-181 (Oxycodegol), in Patients with Moderate to Severe Chronic Low Back Pain.

Publications

Measuring Opioid Withdrawal in a Phase 3 Study of a New Analgesic, NKTR-181 (Oxycodegol), in Patients with Moderate to Severe Chronic Low Back Pain.

Similar Datasets

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