Discontinuation vs Continuation of Long-term Opioid Therapy in Suboptimal and Optimal Responders With Chronic Pain

This was a multicenter, randomized, double-blind, placebo-controlled study which consisted of a common Screening Visit for all subjects, then different schedules for Optimal and Suboptimal Responders, followed by a common schedule for the Blinded Structured Opioid Discontinuation Period (BSODP) and Follow-up Period. The original protocol (10 Jan 2016) was amended twice: Amendment 1 (07 Jul 2016) and Amendment 2 (08 Feb 2017). Screening of subjects only started after Amendment 1 approval. Approximately half the subjects were screened under Amendment 1 and half under Amendment 2. The original statistical analysis plan (SAP) was amended twice as well based on the protocol amendments. The current SAP is version 1.3, dated 11 April 2018, which added a section to list the analyses that were not being completed as a result of the premature termination of this study. The duration of the entire study for each subject was approximately 33 to 37 weeks. For Suboptimal Responders: the study duration included Screening Period of up to 3 weeks, Run-in Period of 1 week, Baseline Period of 1 week, Blinded Structured Opioid Discontinuation Period of 24 weeks, and Follow-up Period of 4 weeks. For Optimal Responders: the study duration included Screening Period of up to 3 weeks, Observation Period of 1 week, Taper Period up to 2 weeks, Open Label Titration Period of 3 weeks, Blinded Structured Opioid Discontinuation Period of 24 weeks, and Follow-up Period of 4 weeks. The primary endpoint was the change in the mean Average PI score on the 0-10 Numerical Ratings Scale (NRS) from Baseline to the 1 week period before the Week 12 visit. Data were summarized using descriptive statistics (number of observations \[n\], mean, standard deviation, median, first and third quartiles, minimum, and maximum for continuous variables; and frequency and percentage for categorical variables). Due to the inability to recruit a sufficient number of subjects over an acceptable period of time, the study was terminated prematurely and efficacy analyses were reduced and only a brief summary of the statistical analyses of the primary endpoint in each group (Suboptimal Responders and Optimal Responders) were performed.