This double-blind, placebo-controlled study evaluated the efficacy and safety of
hydrocodone extended release (ER) developed with abuse-deterrence technology to provide sustained
pain relief and limit effects of alcohol and
tablet manipulation on drug release. Eligible patients with chronic moderate-to-severe low back or
osteoarthritis pain were titrated to an
analgesic dose of
hydrocodone ER (15-90 mg) and randomized to placebo or
hydrocodone ER every 12 hours. The primary efficacy measure was change from baseline to week 12 in weekly average
pain intensity (API; 0=no
pain, 10=worst
pain imaginable). Secondary measures included percentage of patients with >33% and >50% increases from baseline in weekly API, change from baseline in weekly worst
pain intensity, supplemental
opioid usage, aberrant
drug-use behaviors, and adverse events. Overall, 294 patients were randomized and received ≥1 dose of placebo (n=148) or
hydrocodone ER (n=146). Weekly API did not differ significantly between
hydrocodone ER and placebo at week 12 (P=0.134); although, in post hoc analyses, the change in weekly API was significantly lower with
hydrocodone ER when excluding the lowest dose (15 mg; least squares mean, -0.20 vs 0.40; P=0.032). Significantly more patients had >33% and >50% increase in weekly API with placebo (P<0.05), and mean weekly worst
pain intensity was significantly lower with
hydrocodone ER at week 12 (P=0.026). Supplemental medication usage was higher with placebo (86%) than
hydrocodone ER (79%). Incidence of aberrant
drug-use behaviors was low, and adverse events were similar between groups. This study did not meet the primary endpoint, although results support the effectiveness of this
hydrocodone ER formulation in managing chronic low back or
osteoarthritis pain. Use of the
hydrocodone ER 15-mg dose, a robust placebo response, and use of supplemental
analgesics, particularly in the placebo group, may have limited detection of a statistically significant treatment effect, and additional research is needed to clarify these findings.