Investigational Submicron Diclofenac Reduces Use of Opioid Rescue Medication in Post-Surgical Pain in a Phase 3 Study


Late-Stage Data Presented at PAINWeek 2013

LAS VEGAS, September 5, 2013 — Iroko Pharmaceuticals, LLC, a global specialty pharmaceutical company dedicated to advancing the science of analgesia, announced today that the company’s investigational, non-steroidal anti-inflammatory drug (NSAID), submicron diclofenac, reduced the use of opioid rescue medication in patients with acute pain following bunionectomy surgery. Specifically, the study showed that significantly fewer patients who received submicron particle diclofenac capsules 35 mg (82 percent; P=0.002) or 18 mg (85 percent; P=0.005), or who received active comparator celecoxib (85 percent; P=0.006), required opioid-containing rescue medication for pain versus placebo (97 percent).

These data were presented today at PAINWeek 2013, in Las Vegas, Nevada, and are included in the company’s New Drug Application (NDA) for submicron diclofenac, accepted for filing by the US Food and Drug Administration (FDA) in February 2013.

“While opioids are commonly used for the treatment of severe post-surgical pain, physicians often look for options to minimize their use due to the associated risks,” said Dr. Clarence Young, Chief Medical Officer of Iroko. “In this study, submicron diclofenac reduced the need for opioid use and also delayed the need for rescue use of these medications, further suggesting that it could potentially play an important role in pain management following surgery.”

Patients given submicron-particle diclofenac capsules 35 mg (5.9 h; P<0.001) or 18 mg (9.1 h; P<0.001) were able to delay use of opioid rescue medications, requiring their use at later times compared to those given placebo (2.7 h). Opioid rescue medication was also used at later times in patients given celecoxib (4.9 h; P=0.013).

“Delaying or avoiding opioid use in pain management remains a key objective in patient care,” said Srinivas Nalamachu, MD, assistant clinical professor, University of Kansas Medical Center, and one of the study authors. “As a result, there is a major need for new medications that can deliver effective relief from acute pain at low doses while minimizing the necessity of opioid use. These data further suggest that lower-dose submicron particle diclofenac capsules may be a viable option for patients experiencing acute pain following surgery.”

About the Phase 3 Study

These results were from a Phase 3, randomized, double-blind, multiple-dose, parallel-group, active- and placebo-controlled study that enrolled 428 otherwise healthy adults who developed significant pain following surgery (bunionectomy with internal fixation) under regional anesthesia, experiencing a pain intensity rating of ≥40 mm on a 100-mm visual analog scale (VAS) during the nine-hour period after anesthesia was discontinued. Participants in the study were randomly assigned to receive submicron-particle diclofenac capsules 18 or 35 mg three times a day, celecoxib 400 mg as a loading dose followed by 200-mg twice a day, or placebo.

The primary endpoint was the sum of pain intensity differences measured by VAS at intervals during the first 48 hours after discontinuation of general anesthesia (VASSPID‑48).

Submicron particle diclofenac capsules 35 mg and 18 mg were associated with lower pain intensity versus placebo (P<0.001 and P=0.011, respectively), with the onset of analgesia in the 35 mg group as early as 30 minutes after dosing.

Secondary endpoints included pain intensity difference at each scheduled assessment, time to first use of rescue medication, and proportion of patients using rescue medication. One oral tablet of hydrocodone/acetaminophen (10 mg/325 mg) every 4 to 6 hours as needed was permitted as initial rescue medication for patients whose pain was not adequately relieved by study medication. Patients were encouraged to wait at least 1 hour after the first dose of study medication before taking the first dose of rescue medication. The total daily dosage of rescue medication was limited to ≤6 tablets during the study.

The incidence of adverse events in the study was generally comparable across treatment groups. The most common adverse events for all treatment groups were post-procedural swelling, nausea, headache and dizziness. A single serious adverse event, deep venous thrombosis, was reported in the study for one subject in the celecoxib treatment group.

About Lower Dose Submicron NSAIDs

The risk of adverse events, including upper gastrointestinal ulcers[1], gastrointestinal bleeds[2], and cardiovascular events[3] associated with currently marketed NSAIDs is higher among patients receiving higher doses of NSAIDs[1]. Iroko is at the forefront of developing lower-dose submicron NSAIDs – new drug products based on existing NSAIDs – that are designed to provide effective pain relief at lower doses than existing commercially available NSAID oral drug products. These lower dose submicron NSAIDs are being developed by Iroko, using iCeutica Pty Ltd’s proprietary SoluMatrix™ technology, licensed for exclusive use in NSAIDs to Iroko. The SoluMatrix™ technology alters the pharmacokinetic absorption properties of NSAIDs by reducing drug particles to finer particles that are at least 10 times smaller than standard oral NSAID formulations, thereby enhancing drug dissolution and promoting absorption.

About Iroko Pharmaceuticals, LLC

Iroko is a global specialty pharmaceutical company, based in Philadelphia, dedicated to advancing the science of analgesia. The company acquires, develops and globally commercializes currently marketed products. In addition to the Iroko products that are marketed worldwide, the company has a robust pipeline of late-stage submicron NSAID product candidates. For more information, visit www.iroko.com.

Contacts:

Jessica Donnelly for Iroko Pharmaceuticals, LLC, 212-798-9819
Kate de Santis, Iroko Pharmaceuticals, LLC, 267-546-1682

References

  1. Risser A, Donovan D, Heintzman J, Page T. NSAID prescribing precautions. Am Fam Physician. 2009;80(12):1371-1378.
  2. Rahme E, Joseph L, Kong SX, Watson DJ, LeLorier J. Cost of prescribed NSAID-related gastrointestinal adverse events in elderly patients. Br J Clin Pharmacol. 2001;52(2):185-192.
  3. Howes LG. Selective COX-2 inhibitors, NSAIDs and cardiovascular events – is celecoxib the safest choice? Ther Clin Risk Manag. 2007;3(5):831-845.