The efficacy and safety of hydrocodone bitartrate extended-release tablets 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 hydrocodone bitartrate extended-release tablets. Patients were dosed once daily with hydrocodone bitartrate extended-release tablets (20 mg to 120 mg). Patients stopped their prior opioid analgesics and/or nonopioid analgesics prior to starting hydrocodone bitartrate extended-release tablet 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, hydrocodone bitartrate extended-release tablets dose was allowed to be increased once every 3 to 5 days until a stabilized and tolerable dose was identified. During the dose-titration period, 65% of the patients achieved a stable hydrocodone bitartrate extended-release tablets 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 hydrocodone bitartrate extended-release tablets (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 to 10 numerical rating scale) and acceptable tolerability of hydrocodone bitartrate extended-release tablets. Patients randomized to placebo were given a blinded taper of hydrocodone bitartrate extended-release tablets according to a pre-specified tapering schedule, 3 days on each step-down dose (reduced by 25% to 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 hydrocodone bitartrate extended-release tablets dose. During the double-blind period, 229 treated patients (77%) completed the 12-week treatment with hydrocodone bitartrate extended-release tablets and 210 patients (72%) completed on placebo. Overall, 10% of patients discontinued due to lack of therapeutic effect (5% in hydrocodone bitartrate extended-release patients and 15% in placebo patients); 5% of patients discontinued due to adverse events (6% in hydrocodone bitartrate extended-release tablet treated patients and 3% in placebo patients). 

Hydrocodone bitartrate extended-release tablets 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 hydrocodone bitartrate extended-release tablets 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