The efficacy of TARGINIQ ER was evaluated in one 12-week, randomized, double-blind, placebo-controlled clinical trial in opioid-experienced patients with uncontrolled moderate to severe chronic low back pain.

12-Week Study in Opioid-Experienced Patients with Uncontrolled Chronic Low Back Pain   
A total of 1095 patients (mean age = 52 years [range 20-88]; 45% male and 55% female) with uncontrolled moderate to severe chronic low back pain entered an open-label, dose-titration period for up to four weeks. Patients initiated TARGINIQ ER therapy at an oxycodone dose approximately equivalent to their current therapy [see Dosage and Administration (2.1)]. The dose of TARGINIQ ER could be up-titrated to a maximum of 40/20 mg twice daily by the investigator every 1-2 days as needed based on efficacy, safety, and tolerability considerations or down-titrated at any time for safety and/or tolerability reasons. During open-label titration, subjects were allowed supplemental pain medication (immediate-release oxycodone HCl 5 mg capsules) for low back pain every 4 hours as needed up to 8 capsules per day.

Fifty-five percent (55%) of patients who entered the open-label titration period achieved adequate analgesia and tolerability on TARGINIQ ER and were then randomized to their final titrated dose of TARGINIQ ER or matching placebo for 12 weeks of double-blind treatment. Nine percent (9%) of patients discontinued from the open-label titration period due to an adverse event; 10% discontinued due to lack of a therapeutic effect, and 11% discontinued for other reasons. Sixteen (16%) percent did not qualify for randomization. During double-blind treatment, subjects were allowed one capsule of supplemental pain medication (immediate-release oxycodone HCl 5 mg capsules) for low back pain as needed, up to 2 capsules per day.

Of the 298 patients randomized to TARGINIQ ER, 73% of the patients completed the 12-week double-blind treatment on study drug. Of the 302 patients randomized to placebo, 60% of the patients completed the study. Fewer patients randomized to TARGINIQ ER discontinued due to lack of efficacy compared to placebo, 10% versus 24%. Discontinuation due to adverse events was the same for both TARGINIQ ER (8%) and placebo (8%).

Of the patients who were randomized, pain scores were similar at screening and end of the open-label titration for TARGINIQ ER and placebo subjects. The mean average pain over the last 24 hours (SE) scores were 7.0 (0.06) and 7.1 (0.06) at screening and 3.1 (0.06) and 3.1 (0.06) at pre-randomization (beginning of double-blind phase) for the TARGINIQ ER and placebo groups, respectively.

The mean score of average pain over the last 24 hours at the end of the study (Week 12/Early Termination) was statistically significantly lower in patients treated with TARGINIQ ER (SE), 3.9 (0.1), compared to patients treated with placebo (SE), 4.3 (0.1).

A plot of distribution of responders based on pain intensity at week 12 is shown in Figure 4 below. The figure is cumulative, such that patients whose change from baseline, for example 50%, are also included at every level of improvement below 50%. Patients who did not complete the study were assigned 0% improvement. A higher proportion of patients treated with TARGINIQ ER (55%) had at least a 30% reduction in pain score from screening to week 12 compared to placebo patients (41%). Also, a higher proportion of patients treated with TARGINIQ ER (37%) had at least a 50% reduction in pain score from screening to week 12 compared to placebo patients (25%).

Figure 4. Plot of Distribution of Responders Based on Pain Intensity at Week 12