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An enhanced bunionectomy model as a potential tool for early decision-making in the development of new analgesics

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Abstract

Background

Bunionectomy has been used as a model of postoperative pain for opioids and nonsteroidal anti-inflammatory drugs/cyclooxygenase-2 inhibitors with a fast onset of analgesia. The present study was conducted to assess whether the utility of the model can be broadened in assessing the efficacy of analgesics with diverse mechanisms and pharmacokinetic profiles in drug development and to enhance the sensitivity of a bunionectomy model.

Methods

This was a single center, randomized, double-blind, placebo-controlled, three-arm, parallel group methodology study to evaluate the effects of pregabalin and naproxen sodium on postoperative pain following bunionectomy. Patients (n=100) were randomized 1:1:1 to three treatments (administered 1 hour before and at defined intervals after surgery): pregabalin 300 mg before surgery and 150 mg every 8 hours; naproxen sodium 550 mg before surgery and 550 mg every 12 hours; or placebo in a double-dummy fashion. Primary endpoints were patient-controlled analgesic (PCA) hydromorphone consumption and the time to first PCA hydromorphone use postsurgery over 24 hours.

Results

Of the 100 patients randomized, 96 completed the study. Relative to placebo, pregabalin and naproxen sodium, respectively, reduced PCA hydromorphone consumption by 51% (P=0.005) and 65% (P<0.001) and increased the median time to first use of PCA hydromorphone by 1.5 hours (P=0.004) and 3.7 hours (P<0.001). Both drugs significantly (P<0.050) decreased use of oral opioid rescue medication over 24–48 hours postsurgery relative to placebo. Although there were no statistically significant differences between naproxen sodium and pregabalin in opioid consumption and global evaluation of medication, overall naproxen sodium appeared to be more effective at reducing pain.

Conclusions

The model provided a sensitive method for evaluating efficacy of compounds with diverse mechanisms and pharmacokinetic profiles. The robustness of the enhanced pain model renders bunionectomy pain a valuable tool to assess novel analgesic compounds in small numbers of subjects early in drug development.

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Authors and Affiliations

  1. CNS/Pain and Translational Medicine, Johnson & Johnson Pharmaceutical Research and Development, LLC, Welsh & McKean Roads, PO Box 776, Spring House, PA, 19477-0776, USA

    Hao Wang

  2. Department of Experimental Medicine, Merck Research Laboratories, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USA

    Suzanne Lukac, Chan Beals, Melissa Drexel, Marcella Ruddy & Gary Herman

  3. Department of Biostatistics and Research Decision Sciences-Experimental Medicine, Merck Research Laboratories, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USA

    Cynthia Gargano

  4. Lifetree Clinical Research, Salt Lake City, Utah, USA

    Alice Jackson, Robert Medve & Lynn Webster

  5. Clinical Research Operations US - Experimental Medicine, Merck Research Laboratories, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USA

    Patricia Smiley

  6. Medical Communications Department, Merck Research Laboratories, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USA

    Amy O. Johnson-Levonas

  7. Department of Bone, Respiratory, Immunology, and Endocrine Research, Merck Research Laboratories, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USA

    Alise Reicin

Authors
  1. Hao Wang
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  2. Cynthia Gargano
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  3. Suzanne Lukac
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Correspondence to Hao Wang.

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Wang, H., Gargano, C., Lukac, S. et al. An enhanced bunionectomy model as a potential tool for early decision-making in the development of new analgesics. Adv Therapy 27, 963–980 (2010). https://doi.org/10.1007/s12325-010-0084-8

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  • DOI: https://doi.org/10.1007/s12325-010-0084-8

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