The efficacy and tolerability of multiple-dose tapentadol immediate release for the relief of acute pain following orthopedic (bunionectomy) surgery .
OBJECTIVE
Tapentadol is a new, centrally acting analgesic with two mechanisms of action, combining μ-opioid agonism and norepinephrine reuptake inhibition in a single molecule. This study assessed tapentadol immediate release (IR) in patients with postsurgical orthopedic pain.


METHODS
This randomized, double-blind, phase II study involved patients with moderate-to-severe pain after bunionectomy surgery (first metatarsal with osteotomy). Patients (N = 269) were randomly assigned to receive tapentadol IR 50 or 100 mg, oxycodone HCl IR 10 mg, or placebo; the study drug was taken every 4-6 h, over a 72-h period starting 1 day after surgery (Evaluation Day 2). The primary endpoint was the sum of pain intensity over 24 h (SPI-24) on the second day after randomization (Evaluation Day 3). Potential limitations of this study included the use of rescue medication and the fact that it was not powered to statistically compare between-group differences in tolerability measures.


RESULTS
Mean (standard deviation [SD]) SPI-24 values on Evaluation Day 3 were significantly lower for tapentadol IR (50 mg: 33.6 [19.7], p = 0.0133; 100 mg: 29.2 [15.2], p = 0.0001) and oxycodone HCl IR 10 mg (35.7 [17.2]; nominal p = 0.0365) compared with placebo (41.9 [17.7]). The most common treatment-emergent adverse events for all treatment groups were characteristic of drugs with μ-opioid agonist activity. While providing similar analgesic efficacy, tapentadol IR 50 mg was associated with lower rates of nausea (46.3% vs. 71.6% for oxycodone HCl IR 10 mg), dizziness (32.8% vs. 56.7%), vomiting (16.4% vs. 38.8%), and constipation (6.0% vs. 17.9%), and a similar rate of somnolence (28.4% vs. 26.9%) compared with oxycodone HCl IR 10 mg.


CONCLUSIONS
Tapentadol IR 50 and 100 mg and oxycodone HCl IR 10 mg were effective in this study for the relief of acute postoperative pain following bunionectomy. The study results suggest improved gastrointestinal tolerability of tapentadol IR 50 mg compared with oxycodone at a dose showing comparable efficacy.
Grunenthal GmbH, Aachen, Germany. jens-ulrich.stegmann@grunenthal.com
Jens-Ulrich
JU
Stegmann
Horst
H
Weber
Achim
A
Steup
Akiko
A
Okamoto
David
D
Upmalis
Stephen
S
Daniels
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006215:Hallux Valgus / Q000150:complications / Q000601:surgery*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019637:Orthopedic Procedures / Q000009:adverse effects / Q000534:rehabilitation; D010149:Postoperative Pain / Q000188:drug therapy*; D010636:Phenols / Q000008:administration & dosage* / Q000009:adverse effects*; D010919:Placebos; D000077432:Tapentadol; D016896:Treatment Outcome; D055815:Young Adult
D000701:Analgesics, Opioid; D010636:Phenols; D010919:Placebos; D000077432:Tapentadol