Onset of action of diclofenac potassium liquid-filled capsules in dental surgery patients

Abstract

Objective:

Diclofenac potassium soft gelatin capsules (DPSGC) are a low-dose, liquid-filled formulation that uses patented dispersion technology to facilitate rapid and consistent gastrointestinal absorption. Onset of pain relief experienced by patients receiving DPSGC was evaluated in two dental pain studies. Confirmed perceptible pain relief was evaluated in a post hoc analysis from these randomized controlled trials.

Research design and methods:

Adult patients (n = 514) were enrolled in two multicenter, parallel group, double-blind, placebo-controlled studies. Patients undergoing third molar extraction and experiencing a requisite level of pain (≥50 mm on a 100-mm visual analog scale within 4 hours post-surgery) were randomized to receive single doses of DPSGC 25 mg, 50 mg, 100 mg, or placebo. Pain was assessed at baseline and during 6 hours after dosing. Times to onset of perceptible and meaningful pain relief were recorded using the two-stopwatch method. Confirmed perceptible pain relief was determined in the DPSGC and placebo groups by calculating the median time to onset of perceptible pain relief (first stopwatch) in only those individuals who reported meaningful pain relief (second stopwatch).

Results:

More than 80% of patients achieved confirmed perceptible pain relief in the DPSGC groups compared with less than 30% of patients in the placebo group (Study 1 and Study 2, p < 0.0001). The median time to onset of confirmed perceptible pain relief in the two studies was less than 30 minutes for patients receiving any dose of DPSGC and more than 360 minutes in the placebo group (Study 1 and Study 2, p < 0.0001). DPSGC was well tolerated and no serious adverse events were reported. Study design limitations include the short duration of the trial and evaluation of a relatively limited patient population.

Conclusions:

These results indicate that DPSGC was efficacious in providing a rapid onset of confirmed perceptible pain relief within 30 minutes of administration in these single dose postoperative dental pain studies.

Key words::

• Acute pain
• Analgesics
• Dental pain
• Diclofenac
• NSAIDs
• Oral surgery

Transparency

Declaration of funding

This research was supported by Xanodyne Pharmaceuticals, Inc.

Declaration of financial/other relationships

J.R.Z. has disclosed that he has received grant/research support from Applied Analytical Industries, Inc., and that he has participated in speakers bureaus for Applied Analytical Industries, Inc., and Pfizer. R.J.N. has no disclosures to report. W.K.S. has disclosed that he has acted as a consultant on behalf of RRD International and Xanodyne Pharmaceuticals, Inc. S.E.B. is a full-time employee of Xanodyne Pharmaceuticals, Inc. E.V.H. has disclosed that he has received grant/research support from Applied Analytical Industries, Inc.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgment

The authors would like to thank the participants, coordinators, nurses, and investigators involved in these studies. They would also like to thank Teresa A. Oblak, PhD, of The JB Ashtin Group, Inc., who assisted in the preparation of this manuscript.

Some of the data reported in this article were previously presented in poster form at the American Pain Society Annual Scientific Meeting, Tampa, FL, USA, 8–10 May 2008; American Society of Pain Educators Meeting, Las Vegas, NV, USA, 4–7 September 2008; and the American Academy of Pain Medicine Meeting, Honolulu, HI, USA, 27–31 January 2009.

All authors have participated in the study and were involved in critically reviewing, revising, and approving the manuscript as submitted. Medical writing services from The JB Ashtin Group, Inc., Plymouth, Michigan, were funded by Xanodyne Pharmaceuticals, Inc.

Notes

* Zipsor is a registered trademark of Xanodyne Pharmaceuticals, Inc., Newport, KY, USA.

† ProSorb is a registered trade name of Xanodyne Pharmaceuticals, Inc, licensed from AAIPharma, Inc., Wilmington, NC, USA.