Once-daily OROS hydromorphone ER compared with placebo in opioid-tolerant patients with chronic low back pain

Curr Med Res Opin. 2010 Jun;26(6):1505-18. doi: 10.1185/03007995.2010.484723.

Abstract

Objective: This multicenter, double-blind, placebo-controlled study using a randomized withdrawal design evaluated the efficacy and safety of once-daily OROS hydromorphone ER in the treatment of opioid-tolerant patients with chronic moderate-to-severe low back pain (LBP).

Main outcome measures: The primary efficacy assessment was mean change in pain intensity based on patient diary Numeric Rating Scale (NRS) scores from baseline to final visit of the 12-week double-blind phase. Secondary endpoints included mean change from baseline to each visit in patient diary NRS scores; and office NRS scores; time to treatment failure; Patient Global Assessment; rescue medication use; and Roland Morris Disability Questionnaire total scores.

Clinical trial registration: ClinicalTrials.gov NCT00549042.

Results: For the primary outcome measure, hydromorphone ER significantly reduced pain intensity compared to placebo (p < 0.001). Median diary NRS score change from baseline to endpoint was significantly lower for OROS [corrected] hydromorphone ER (0.2 units) compared to placebo (1.6 units). [corrected] A significantly higher proportion of hydromorphone ER (60.6%) vs. placebo (42.9%) patients had at least a 30% reduction in diary NRS pain score from screening to endpoint (p < 0.01). Hydromorphone ER was well-tolerated, although 60 (13%) discontinued during the enrichment phase for adverse events and more active (9, 6.7%) than placebo (4, 3.0%) patients discontinued treatment for adverse events during the randomized phase.

Conclusions: These results provide evidence for the efficacy and safety of hydromorphone ER in opioid-tolerant patients with chronic moderate-to-severe LBP. Potential limitations include the shortened dose-conversion/titration phase, limiting the daily allowable dose of hydromorphone ER to 64 mg, and the allowance of limited rescue medication throughout the entire double-blind phase. Other trial design elements such as the use of an enrichment phase and the inclusion of only opioid tolerant patients may limit the generalizability of these results.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacology*
  • Chronic Disease
  • Delayed-Action Preparations
  • Drug Tolerance
  • Female
  • Humans
  • Hydromorphone / administration & dosage
  • Hydromorphone / pharmacology*
  • Low Back Pain / drug therapy*
  • Male
  • Middle Aged
  • Placebos
  • Quebec
  • Treatment Outcome
  • Young Adult

Substances

  • Analgesics, Opioid
  • Delayed-Action Preparations
  • Placebos
  • Hydromorphone

Associated data

  • ClinicalTrials.gov/NCT00549042