An enriched-enrollment, randomized-withdrawal, double-blind, placebo-controlled, parallel group, study was conducted in 740 patients with persistent, moderate-to-severe chronic lower back pain, with inadequate pain control from their prior therapy. During screening, patients stopped their prior opioid analgesics and/or non-opioid analgesics prior to starting XTAMPZA ER treatment. Patients were titrated to a stable and tolerated dose between 18 mg (equivalent to 20 mg oxycodone HCl) twice daily and 72 mg (equivalent to 80 mg oxycodone HCl) twice daily of XTAMPZA ER in an open-label fashion during the first six weeks of the trial. Optional use of rescue medication (acetaminophen 500 mg tablets) up to 2 tablets every 4-6 hours was permitted during the dose titration phase, up to 2000 mg per day. XTAMPZA ER was titrated once every three to seven days until a stable and tolerable dose was identified (maximum dose of 72 mg [equivalent to 80 mg oxycodone HCl] twice daily). 

Following the titration phase, 389 subjects (53%) met the study randomization criteria of adequate analgesia (pain reduction of at least 2 points from screening baseline to a score of 4 or less on a 0-10 numerical rating scale) and acceptable tolerability of XTAMPZA ER and entered the randomized, double-blind maintenance phase. Subjects discontinued from the dose-titration phase for the following reasons: failure to meet entrance criteria (18%), adverse events (13%), subject request (7%) and lack of efficacy (5%). Patients were randomized at a ratio of 1:1 into a 12-week double-blind maintenance phase with their fixed stable dose of XTAMPZA ER (or matching placebo). Patients randomized to placebo were given a blinded taper of XTAMPZA ER according to a prespecified tapering schedule; XTAMPZA ER was decreased by 25% to 35% every 5 days for the higher doses of XTAMPZA ER and up to 50% every 5 days for the mid-to-lower doses of XTAMPZA ER over the first 20 days of the double-blind maintenance phase. Patients were allowed to use rescue medication (acetaminophen 500 mg tablets) up to a maximum dose of 2000 mg per day. During the double-blind maintenance phase, 122 patients (63%) completed the 12-week treatment with XTAMPZA ER and 100 (51%) completed with placebo. Overall, 11% of patients discontinued due to lack of efficacy (4% of XTAMPZA ER patients and 17% of placebo patients), and 7% discontinued due to adverse events (7% of XTAMPZA ER patients and 7% of placebo patients).

In this study, there was a significant difference in pain reduction, favoring XTAMPZA ER, between XTAMPZA ER (doses of 36-144 mg per day, equivalent to 40-160 mg of oxycodone HCl) and placebo, based on the primary endpoint of change in average pain intensity from randomization baseline to Week 12 of the double-blind maintenance phase.

The proportion of patients (responders) in each group who demonstrated improvement in their weekly average pain scores from screening baseline to Week 12, is shown in Figure 2. The figure is cumulative, so that patients whose change from screening is, for example, 30%, are also included at every level of improvement below 30%. Patients who did not complete the study were classified as non-responders. Treatment with XTAMPZA ER resulted in a higher proportion of responders, defined as patients with at least a 30% and 50% improvement as compared to placebo.

Figure 2: Responder Analysis for Pain Intensity: Percent Reduction/Improvement (Intent-to-Treat Population)