Introduction The efficacy and safety of one dose of controlled-release hydrocodone 15 mg/acetaminophen 500 mg (HC/APAP CR) were evaluated following bunionectomy.

Methods Subjects were recruited from 4 US sites; each site's IRB approved the study protocol and informed consent. 212 subjects were randomized to 1 HC/APAP CR tablet plus placebo (n=70), 2 HC/APAP CR tablets (n=70), or 2 placebo tablets (n=72) upon onset of moderate or severe pain within 6 hours of surgery. Subjects were treated for 3 days; results are from the first 12 hours of treatment. The primary endpoint was time-interval weighted sum of pain relief (TOTPAR) over the first 12 hours. Subjects received rescue medication as needed.

Results 211/212 subjects completed the study; 140 received at least 2 doses of HC/APAP CR. Baseline variables were similar among groups. Most subjects were female (91%) and the mean age was 40.3 years. Subjects receiving HC/APAP CR showed statistically significant improvement in all efficacy variables shown in Table 1.  

Table 1. Efficacy Variable Results

 

Variables	Placebo n=72	1-Tablet HC/APAP CR n=70	2-Tablet HC/APAP CR n=70
TOTPAR score, mean (SE) (higher scores indicate more pain relief)	2.2 (0.98)	6.4 (0.99)*	13.3 (1.00)*†
Perceived pain relief, n (%)	28/70 (40%)	52 (74%)*	60 (86%)*
Meaningful pain relief, n (%)	11/70 (16%)	28 (40%)*	45 (64%)*†
Median time to rescue medication, minutes	101	131*	251*†

    * p<0.01 vs. placebo

    † p<0.01 vs. 1-tablet  

Time to perceptible pain relief was <40 minutes. Incidence of adverse events was significantly higher for subjects receiving HC/APAP CR versus placebo; the most common adverse events were nausea, vomiting, headache, dizziness, somnolence, pruritus, and pain.

Conclusions One or 2 tablets of controlled-release HC 15 mg/APAP 500 mg provided significantly better pain relief for acute bunionectomy pain versus placebo. Two tablets provided consistently superior relief to 1 tablet.