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

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:

Trial registration: ClinicalTrials.gov identifier: 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 hydromorphone ER (0.2 units) compared to placebo (1.2 units). 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 generalizabilty of these results.

Key words::

• Analgesics
• Chronic low back pain
• Hydromorphone
• Opioid
• Pain

View correction statement:

Erratum

Transparency

Declaration of funding

This study was supported by Neuromed Pharmaceuticals. Funding for editorial support for this manuscript was provided by Neuromed and Covidien Pharmaceuticals.

Declaration of financial/other relationships

M.H. has disclosed that he has been a Consultant to Alza, Neuromed and Covidien Pharmaceuticals; and an investigator in several trials conducted by Knoll, Alza and Neuromed to investigate the safety and efficacy of OROS hydromorphone ER. A.K., principal investigator of over 330 clinical trials sponsored by over 55 pharmaceutical companies and 30 contract research organizations, has disclosed that he has done no compensated consulting or speaking on their behalf. He has disclosed that he has been a principal investigator during two hydromorphone ER phase III trials enrolling a total of 25 patients. M.K. has disclosed that he is an employee of Applied Clinical Intelligence; ACI was the data management and statistical programming CRO used for this trial. S.L. has disclosed that he is a former employee and shareholder of Neuromed, which sponsored the development of this drug.

Some peer reviewers receive honoraria from CMRO for their review work. The peer reviewers of this paper have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors acknowledge editorial support provided by Synchrony Medical LLC, West Chester, PA funded by Neuromed and Covidien.

Data contained in this paper were previously presented at the 28th Annual Scientific Meeting of the American Pain Society; May 6–9, 2009; San Diego, CA, USA.

Notes

*Mallinckrodt Inc., a Covidien company, Hazelwood, MO, USA.

†Janssen-Cilag outside USA.