Tapentadol, oxycodone or placebo for acute pain of vertebral compression fractures: a randomized Phase IIIb study

SUMMARY

Tapentadol is a centrally acting analgesic that combines µ-opioid receptor agonism with norepinephrine reuptake inhibition. This study evaluated the efficacy and safety of tapentadol immediate-release (IR), oxycodone IR or placebo in subjects with acute pain from vertebral compression fracture (VCF) associated with osteoporosis.

Study patients were adults with new onset of pain or acute exacerbation of previous pain from VCF associated with osteoporosis, radiographic confirmation of VCF and back pain intensity of 5 or greater on an 11-point scale from 0 (no pain) to 10 (pain as bad as you can imagine). Patients were randomized to treatment with tapentadol IR (50 mg, then 50 or 75 mg), oxycodone IR (5 mg, then 5 or 10 mg) or placebo every 4-6 h as needed for pain, for up to 10 days. Twice daily, subjects recorded pain intensity on the 11-point scale (numeric rating scale), pain relief on a 5-point scale from 0 (none) to 4 (complete), sleep assessments (morning assessment only) and any episodes of vomiting (evening assessment only).

The study was designed to include 625 subjects, but was stopped after 14 months due to slow enrollment (44 tapentadol IR, 43 oxycodone IR and 21 placebo subjects) and had insufficient statistical power for comparative efficacy analyses. Discontinuation rates in the tapentadol IR, oxycodone IR and placebo groups were 18.2, 27.9 and 9.5%, respectively, often due to adverse events (4.5, 18.6 and 4.8%, respectively). Treatment-emergent adverse-event rates were 63.6, 81.4 and 38.1%, respectively.

In this prematurely terminated study in adults with painful VCF, trends suggested that tapentadol IR was tolerated better than oxycodone IR.