Tolerability, Safety, and Effectiveness of Oxycodone DETERx in Elderly Patients ≥65 Years of Age with Chronic Low Back Pain: A Randomized Controlled Trial

Abstract

Trial design: This was a phase III, randomized withdrawal, double-blind, placebo-controlled, enriched enrollment, parallel-group, multicenter study intended to demonstrate the safety, tolerability, and analgesic efficacy of oxycodone DETERx® (Xtampza™ ER) compared with matching placebo.

Methods: This post hoc analysis was performed using data from a subpopulation of enrolled patients who were ≥65 years of age. The study enrolled male and female patients with a clinical diagnosis of moderate-to-severe chronic low back pain for a minimum of 6 months prior to screening who required around-the-clock opioid therapy. To be eligible for enrollment, patients were required to have an average 24-h pain intensity score of ≥5 and ≤9 on an 11-point (0-10) Pain Intensity-Numerical Rating Scale at the screening visit. The study enrolled both opioid-experienced and opioid-naïve patients. The study consisted of an open-label titration phase followed by a 12-week double-blind maintenance phase. The dose range was 40-160 mg oxycodone hydrochloride equivalent per day. This post hoc analysis evaluated the safety, tolerability, and effectiveness of oxycodone DETERx among patients ≥65 years of age. The effectiveness of oxycodone DETERx was evaluated based on average pain intensity scores, Patient Global Impression of Change, responder analysis, and Kaplan-Meier survival analysis. The safety and tolerability of oxycodone DETERx were also evaluated. Patients were randomized to either oxycodone DETERx or placebo using a blocked randomization scheme in a 1:1 ratio. Randomization was stratified by previous opioid use (naïve or experienced). The study drug was coded in a manner that maintained the blinding. Study personnel and patients remained blinded to the assigned treatments throughout the study.

Results: For this post-hoc analysis, the intent-to-treat and randomized safety populations included 52 patients ≥65 years old, 26 each in the oxycodone DETERx and placebo groups, who participated in the study during the titration phase and were randomized to the double-blind maintenance phase. Clinically important pain reduction from screening was achieved with oxycodone DETERx, with the median pain intensity score decreasing from 7.50 at screening to 2.69 at Week 12. A clinically meaningful treatment difference of -0.9 in pain score between oxycodone DETERx and placebo was observed. All 18 elderly patients who completed the study reported improvement in pain, with 62% showing ≥30% improvement and 54% showing ≥50% improvement in pain intensity compared with patients on placebo (p = 0.0128 and p = 0.0501, respectively). Patients on oxycodone DETERx remained in the study longer than those on placebo. Of the 26 patients ≥65 years old randomized to continue oxycodone DETERx during the double-blind maintenance phase, 18 (69%) completed the study; only two patients (8%) in the oxycodone DETERx group discontinued due to adverse events. The safety and tolerability profiles showed no new or unexpected safety concerns. The adverse event profiles were similar between the titration and double-blind maintenance phases.

Conclusions: Oxycodone DETERx was efficacious and generally well tolerated in patients ≥65 years old.

Trial registration: The study was registered with ClinicalTrials.gov (NCT01685684).

Conflict of interest statement

Conflict of interest

Authors Melinda O’Connor and Scott Lagasse are salaried (including stock) employees of Collegium Pharmaceutical, Inc., the company that funded the study and the writing of this manuscript. At the time this manuscript was written, author Ernest A. Kopecky was a salaried (including stock) employee of Collegium Pharmaceutical, Inc. Ben Vaughn is a salaried employee of Rho, Inc., a contract research organization that performed the statistical analyses for the manuscript. Mr. Vaughn has no personal financial ties to Collegium Pharmaceutical, Inc. and no ownership in any form in Rho, Inc.

Funding

The study was funded by Collegium Pharmaceutical, Inc.

Ethical approval and informed consent

The study was conducted according to Good Clinical Practice guidelines and the Declaration of Helsinki. The clinical protocol for the parent study was reviewed and approved by an institutional review board (Quorum Review IRB, Seattle, WA, USA). All patients provided written consent to participate in the parent study before study-related procedures or assessments were conducted.

Figures

Fig. 1

Patient disposition

Fig. 2

Weekly pain intensity (measured using an 11-point (0–10) numerical rating scale) scores for patients taking oxycodone DETERx by age (intent-to-treat population)

Fig. 3

Responder analysis for pain intensity percent reduction at Week 12 in patients ≥65 years old (intent-to-treat population)

Fig. 4

Time to exit from the study using the Kaplan–Meier method—patients ≥65 years of age