A Phase 2 Study Evaluating the Efficacy and Safety of a Novel, Proprietary, Nano-Formulated, Lower Dose Oral Diclofenac



This article is corrected by:

  1. Errata: Erratum Volume 14, Issue 10, 1615, Article first published online: 16 October 2013

  • Disclosure: Garen Manvelian, MD, is a consultant for Iroko Pharmaceuticals, LLC. Allan Gibofsky, MD, has participated in a scientific advisory board for Iroko Pharmaceuticals, LLC. Stephen Daniels, DO, is an employee of Premier Research Group International, LLC, which was contracted to complete this Phase 2 clinical trial.

Allan Gibofsky, MD, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA. Tel: 212-606-1423; Fax: 212-628-0354; E-mail: gibofskya@hss.edu.


Background.  Safety concerns associated with nonsteroidal anti-inflammatory drugs (NSAIDs) have prompted the development of new formulations that minimize adverse events (AEs) and maintain efficacy.

Objectives.  To determine the analgesic efficacy and safety of an investigational, proprietary, nano-formulated, oral diclofenac (nano-formulated diclofenac) compared with placebo in subjects with acute dental pain.

Methods.  A Phase 2, multisite, randomized, double-blind, single-dose, parallel-group, active- and placebo-controlled study was carried out in 202 subjects (18–50 years old) who had extraction of ≥2 third molars (≥1 had to be a fully or partially impacted mandibular third molar) and experienced moderate to severe pain intensity ≤6 hours postsurgery (NCT00985439). Subjects received nano-formulated diclofenac 35 mg or 18 mg, celecoxib 400 mg, or placebo. The primary efficacy variable was the sum of total pain relief (TOTPAR) over 0–12 hours (TOTPAR-12) after Time 0. Secondary end points included TOTPAR over 0–4 hours (TOTPAR-4), TOTPAR over 0–8 hours (TOTPAR-8), and time to onset of analgesia.

Results.  Mean ± standard deviation TOTPAR-12 for nano-formulated diclofenac 35 mg and 18 mg, celecoxib, and placebo were 16.81 ± 12.76, 17.76 ± 13.76, 14.61 ± 15.05, and 5.65 ± 11.53, respectively (P < 0.001, nano-formulated diclofenac compared with placebo). Similar improvements were observed for TOTPAR-4, TOTPAR-8, mean time to first perceptible pain relief (P < 0.001), and peak relief (P < 0.05). Celecoxib treatment was not statistically different than placebo for these latter two parameters. Treatment-emergent AEs were similar across all treatment groups.

Conclusions.  Lower dose, nano-formulated diclofenac demonstrated good overall efficacy, prompt pain relief, and was well tolerated. These data suggest lower dose nano-formulated NSAIDs could be effective for acute pain and may potentially improve safety and tolerability as a result of using a lower overall dose.