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Safety and Tolerability of Tapentadol Extended Release in Moderate to Severe Chronic Osteoarthritis or Low Back Pain Management: Pooled Analysis of Randomized Controlled Trials

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Abstract

Introduction

This analysis of pooled data from four randomized, controlled-dose adjustment, phase 3 studies (three 15-week, double-blind, placebo- and active-controlled studies and a 1-year, open-label, active-controlled safety study) in patients with chronic osteoarthritis hip or knee pain or low back pain evaluated the safety and tolerability of tapentadol extended release (ER) for the management of moderate to severe, chronic pain.

Methods

In the three 15-week studies, patients were randomized (1:1:1) to twice-daily (bid) doses of placebo, tapentadol ER (100–250 mg), or oxycodone hydrochloride (HCl) controlled release (CR; 20–50 mg). In the 1-year safety study, patients were randomized (4:1) to tapentadol ER (100–250 mg bid) or oxycodone HCl CR (20–50 mg bid). Adverse events (AEs) and discontinuations were recorded in each study; pooled results were analyzed by treatment group.

Results

In the placebo (n = 993), tapentadol ER (n = 1,874), and oxycodone CR (n = 1,224) groups, respectively, 40.7%, 48.4%, and 62.3% of patients discontinued treatment prematurely and 58.7%, 79.0%, and 86.6% of patients experienced ≥1 treatment-emergent AE (TEAE). Incidences of gastrointestinal TEAEs in the placebo, tapentadol ER, and oxycodone CR groups, respectively, were 26.6%, 47.3%, and 65.4%; incidences of nervous system TEAEs were 22.5%, 42.6%, and 45.1%, respectively. Moderate or severe gastrointestinal TEAEs were reported for 10.9% of patients who received placebo, 25.3% of patients who received tapentadol ER, and 42.3% of patients who received oxycodone CR, and moderate or severe nervous system TEAEs were reported for 10.6%, 22.1%, and 25.2% of patients, respectively. In the placebo, tapentadol ER, and oxycodone CR groups, respectively, incidences of gastrointestinal TEAEs leading to study discontinuation were 2.1%, 8.3%, and 24.1%; incidences of nervous system TEAEs leading to discontinuation were 1.4%, 7.9%, and 16.3%, respectively.

Conclusion

Results from this large patient population showed that tapentadol ER (100–250 mg bid) had improved gastrointestinal tolerability compared with oxycodone CR, based on the overall incidence of gastrointestinal TEAEs, the incidence of moderate or severe gastrointestinal TEAEs, and the incidence of gastrointestinal TEAEs leading to discontinuation.

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Acknowledgments

Sponsorship and article processing charges for this study were funded by Janssen Scientific Affairs, LLC, (New Jersey, USA) and Grünenthal GmbH (Aachen, Germany). Medical writing assistance for this study was provided by Megan Knagge, PhD, of MedErgy (Pennsylvania, USA), and funded by Janssen Research & Development, LLC (New Jersey, USA). The authors would like to acknowledge the contributions of Akiko Okamoto of Janssen Research & Development, LLC. All named authors meet the ICMJE criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published.

Conflict of interest

Mila Etropolski is an employee of Janssen Research & Development, LLC, and is a Johnson & Johnson stockholder. Christine Rauschkolb is an employee of Janssen Research & Development, LLC, and is a Johnson & Johnson stockholder. Brigitte Kuperwasser was an employee of Janssen Research & Development, LLC, at the time the work was performed and is a Johnson & Johnson stockholder. Thomas Häufel is an employee of Grünenthal GmbH. Bernd Lange is an employee of Grünenthal GmbH. Frank Laschewski is an employee of Grünenthal GmbH. Maren Flügel was an employee of Grünenthal GmbH at the time the work was performed.

Compliance with ethics guidelines

The analysis in this article is based on previously conducted studies, and does not involve any new studies of human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Janssen Research & Development, LLC, 1125 Trenton Harbourton Rd, Titusville, NJ, 08560, USA

    Mila Etropolski, Brigitte Kuperwasser & Christine Rauschkolb

  2. Global Development, Grünenthal GmbH, Aachen, Germany

    Maren Flügel & Bernd Lange

  3. Global Drug Safety, Grünenthal GmbH, Aachen, Germany

    Thomas Häufel & Frank Laschewski

Authors
  1. Mila Etropolski
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  2. Brigitte Kuperwasser
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  3. Maren Flügel
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  4. Thomas Häufel
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  5. Bernd Lange
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  6. Christine Rauschkolb
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  7. Frank Laschewski
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Corresponding author

Correspondence to Mila Etropolski.

Additional information

Trial Registration: NCT00421928, NCT00486811, NCT00449176, and NCT00361504.

Data in this manuscript were presented in part at the International Association for the Study of Pain’s 13th World Congress on Pain, August 29 to September 2, 2010, Montreal, Canada; at the British Pain Society’s 2010 Annual Scientific Meeting, April 13–16, 2010, Manchester, England; at the 14th World Society of Pain Clinicians Congress, October 28–31, 2010, Beijing, China; and at the 2010 National Conference on Pain for Frontline Practitioners (PAIN Week), September 8–11, 2010, Las Vegas, Nevada.

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Etropolski, M., Kuperwasser, B., Flügel, M. et al. Safety and Tolerability of Tapentadol Extended Release in Moderate to Severe Chronic Osteoarthritis or Low Back Pain Management: Pooled Analysis of Randomized Controlled Trials. Adv Ther 31, 604–620 (2014). https://doi.org/10.1007/s12325-014-0128-6

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