The efficacy and safety of HYSINGLA ER was evaluated in a randomized double-blind, placebo-controlled, multi-center, 12-week clinical trial in both opioid-experienced and opioid-naïve patients with moderate to severe chronic low back pain.

A total of 905 chronic low back pain patients (opioid naive and opioid-experienced) who were not responsive to their prior analgesic therapy entered an open-label conversion and dose-titration period for up to 45 days with HYSINGLA ER. Patients were dosed once daily with HYSINGLA ER (20 to 120 mg). Patients stopped their prior opioid analgesics and/or nonopioid analgesics prior to starting HYSINGLA ER treatment. Optional use of rescue medication (immediate-release oxycodone 5 mg) up to 2 doses (2 tablets) was permitted during the dose titration period. For inadequately controlled pain, HYSINGLA ER dose was allowed to be increased once every 3–5 days until a stabilized and tolerable dose was identified. During the dose-titration period, 65% of the patients achieved a stable HYSINGLA ER dose and entered the double-blind treatment period. The remaining subjects discontinued from the dose-titration period for the following reasons: adverse events (10%); lack of therapeutic effect (5%); confirmed or suspected diversion (3%); subject's choice (5%); lost to follow-up (2%); administrative reasons (2%); and failure to achieve protocol-defined reduction in pain score (7%).

Following the dose titration period, 588 patients (65%) were randomized at a ratio of 1:1 into a 12-week double-blind treatment period with their fixed stabilized dose of HYSINGLA ER (or matching placebo). These patients met the study randomization criteria of adequate analgesia (pain reduction of at least 2 points to a score of 4 or less on a 0-10 numerical rating scale) and acceptable tolerability of HYSINGLA ER. Patients randomized to placebo were given a blinded taper of HYSINGLA ER according to a pre-specified tapering schedule, 3 days on each step-down dose (reduced by 25-50% from the previous dose). Patients were allowed to use rescue medication (immediate-release oxycodone 5 mg) up to 6 doses (6 tablets) per day depending on their randomized HYSINGLA ER dose. During the double-blind period, 229 treated patients (77%) completed the 12-week treatment with HYSINGLA ER and 210 patients (72%) completed on placebo. Overall, 10% of patients discontinued due to lack of therapeutic effect (5% in HYSINGLA patients and 15% in placebo patients); 5% of patients discontinued due to adverse events (6% in HYSINGLA ER treated patients and 3% in placebo patients).

HYSINGLA ER provided greater analgesia compared with placebo. There was a statistically significant difference in the weekly average pain scores at Week 12 between the two groups.

The percentage of patients (responders) in each group who demonstrated improvement in their weekly average pain scores at Week 12, as compared with screening is shown in Figure 4. 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 HYSINGLA ER resulted in a higher proportion of responders, defined as patients with at least a 30% and 50% improvement, as compared with placebo.

Figure 4. Percent Improvement in Pain Intensity