Analgesic efficacy and safety of controlled-release hydrocodone and acetaminophen tablets, dosed twice daily, for moderate to severe mechanical chronic low-back pain: A randomized, double-blind, placebo-controlled withdrawal trial

Analgesic efficacy and safety of hydrocodone/acetaminophen extended-release (HC/APAP CR) was assessed in subjects with moderate-to-severe chronic low-back pain (CLBP). Subjects with CLBP (n=773) were enrolled at 62 sites; study protocol and informed consent were IRB-approved. Study periods were: Washout/Screening, 3-week Active-Drug Open-Label, 12-week Double-Blind in which subjects were randomized to placebo, 1 or 2 tablets HC/APAP CR twice daily, and Taper/Follow-up. Primary efficacy endpoint was mean change from double-blind baseline to final evaluation in Subject's Assessment of CLBP Intensity (VAS). Safety was evaluated by adverse-event (AE) assessment. All results reported are from the Double-Blind period. 511 subjects were randomized and received °Ý1 dose of study drug; data for 507 were evaluated for efficacy. Most subjects were women (59%) and white (87%); mean age 48 years. Baseline variables were similar among the 3 groups. Mean change from baseline CLBP intensity was statistically significantly lower in subjects in the HC/APAP CR groups than in the placebo group (8.6, 2-tablet; 13.3, 1-tablet vs 22.2, placebo; p<0.05); no statistically significant difference was observed between HC/APAP CR groups. The superiority of treatment with both HC/APAP treatments compared to placebo treatment was consistent across multiple secondary efficacy endpoints. 89/169 (53%) subjects in the HC/APAP CR 2-tablet, 75/170 (44%) in the 1-tablet, and 79/172 (46%) in the placebo group reported °Ý1 AE. AEs in °Ý5% of subjects in any treatment group were nausea, constipation, diarrhea, and headache. Nine subjects reported serious AEs (2 in each HC/APAP CR group; 5 in placebo group); 28 subjects discontinued due to AEs (3% in placebo; 6% in 1-tablet; 7% in 2-tablet group). Both HC/APAP CR doses given twice daily were effective treatment for CLBP over the 12-week period. The safety profile of HC/APAP CR was consistent with known profiles of mu-opioid receptor agonists.

Funded by Abbott Laboratories