Efficacy of single-dose, extended-release naproxen sodium 660 mg in postsurgical dental pain: two double-blind, randomized, placebo-controlled trials

Abstract

Objective:

To evaluate the efficacy of a novel formulation of extended-release/immediate-release (ER) naproxen sodium over 24 h in a dental pain model.

Research design and methods:

Two randomized, double-blind, placebo-controlled trials in moderate to severe pain after extraction of one or two impacted third molars (at least one partial mandibular bony impaction). Treatment comprised oral ER naproxen sodium 660 mg (single dose), placebo (both studies) or immediate-release (IR) naproxen sodium 220 mg tid (study 2).

Main outcome measures:

Primary efficacy endpoint: 24-h summed pain intensity difference (SPID). Secondary variables included total pain relief (TOTPAR), use of rescue medication. All treatment-emergent adverse events were recorded.

Clinical trial registration:

NCT00720057 (study 1), NCT01389284 (study 2).

Results:

Primary efficacy analyses: pain intensity was significantly lower over 24 h with ER naproxen sodium vs. placebo (p < 0.001), with significant relief from 15 min (study 2). In study 2, ER naproxen sodium was non-inferior to IR naproxen sodium, reducing pain intensity to a comparable extent over 24 h. TOTPAR was significantly greater with ER and IR naproxen sodium vs. placebo at all time points, with generally comparable differences between active treatments. Significantly more placebo patients required rescue medication vs. ER and IR naproxen sodium from 2–24 h post-dose. Once daily ER naproxen sodium was generally safe and well tolerated, with a similar safety profile to IR naproxen sodium tid.

Limitations:

The studies were single dose, with limited ability to assess efficacy or safety of multiple doses over time. As the imputed pain score meant that estimated treatment differences may have been biased in favor of ER naproxen sodium, a post hoc analysis evaluated the robustness of the results for pain relief.

Conclusions:

A single dose of ER naproxen sodium 660 mg significantly reduced moderate to severe dental pain vs. placebo and was comparable to IR naproxen sodium 220 mg tid. Significant pain relief was experienced from 15 min and sustained over 24 h, resulting in a reduced need for rescue medication. ER naproxen sodium 660 mg once daily is a convenient and effective therapy providing 24 h relief of pain.

Keywords: :

• Naproxen
• Pain
• Randomized controlled trial
• Tooth, impacted

View addendum:

Addendum

Transparency

Declaration of funding

Bayer HealthCare Consumer Care sponsored both of the trials, as well as preparation of the manuscript.

Author contributions: I.L. designed and oversaw both of the studies, while R.A. worked on the statistical plan and data analysis. Both authors reviewed, edited and approved the draft manuscript provided by the medical writer (Deborah Nock, Medical WriteAway, Norwich, UK).

Declaration of financial/other relationships

I.L. and R.A. have disclosed that they are employees of Bayer HealthCare Consumer Care. R.A. has disclosed that he is also a Bayer stock shareholder.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

Medical writing was provided by Deborah Nock (Medical WriteAway, Norwich, UK), funded by Bayer HealthCare Consumer Care.