Javelin Pharmaceuticals Announces Peer-Reviewed Publication of Successful Postoperative Pain Trial with PMI-100/150 (Intranasal Ketamine) in International Journal, ''Acute Pain''CAMBRIDGE, Mass.--(BUSINESS WIRE)--Dec 19, 2007 - Javelin Pharmaceuticals, Inc. today announced that following peer review, its paper "Safety and Efficacy of Intranasal Ketamine for Acute Pain" was published in "Acute Pain" the International Journal of Acute Pain Management. This journal is the official journal of the Special Interest Group on Acute Pain, of the International Association for the Study of Pain - a leading worldwide scientific and professional organization in the field. This Phase 2 study tested 10-30 mg doses of intranasal ketamine in a well-accepted model of acute postoperative pain, molar extraction. Consistent with the Company's prior studies of intranasal ketamine, patients reported rapid (less than 10 minutes) onset of pain relief, generally mild and transient adverse effects, and had no changes in vital signs, oxygen saturation or the nasal mucosa, and no significant dissociative psychological effects. Integrated pain relief scores over 1 and 3 hours after drug dosing were significantly better for ketamine than placebo (P = 0.013 and 0.028, respectively). Pain relief with the highest ketamine dose (50 mg) separated from placebo over 1 hour (P less than 0.01) as well as over 3 hours, over which time the lowest dose was also superior to placebo (P less than 0.05 for both. The paper concluded that intranasal ketamine may offer a safe, nonopiod, patient friendly and needle-free analgesic with efficacy in moderate-to-severe pain. A pivotal Phase 3 study is being planned to facilitate filing a New Drug Application for the treatment of acute moderate-to severe pain. In addition, a Phase 3, multicenter trial of intranasal Ketamine (PMI-150) for breakthrough cancer pain is currently underway and accruing patients.
"Ketamine is widely used at high doses as a general anesthetic, but decades of experience with its use at low, subanesthetic doses have proven its value for analgesia," said Dr. Daniel Carr, Javelin's CEO/CMO. "While the literature clearly shows the merit of subanesthetic doses of ketamine for pain relief and reduction of morphine requirements after a variety of operations, we believe our study is the first to employ intranasal ketamine for relief of moderate-to-severe pain following molar extraction. Our results in this widely accepted, well-validated model of postoperative pain extend the clinical literature and show this product candidate is efficacious at low, well-tolerated doses."
About the Study
The safety and analgesic efficacy of intranasal ketamine (10 mg, 30 mg, and 50 mg) and placebo were evaluated in a randomized, double-blind, single-dose, parallel study in 40 patients undergoing removal of 2-4 impacted third molars. The primary endpoint was analgesic efficacy assessed over a 3 hour period following drug administration. Safety was evaluated through adverse event reporting, vital signs, pulse oximetry, nasal assessments, and a standard dissociative side effects questionnaire.
Ketamine delivered intranasally was well tolerated. Statistically significant analgesia, superior to placebo, was observed with the highest dose tested, 50 mg, over a 3 hour period. Rapid onset of analgesia was reported (less than10 min), and meaningful pain relief was achieved within 15 min of the 50 mg dose. Analysis of pain relief over a 1 hour period after drug administration also indicated significant differences between treatment groups (P = 0.013), with the 50 mg ketamine group clearly separating from placebo (P less then 0.01). The majority of adverse events were mild/weak and transient. No untoward effects were observed on vital signs, pulse oximetry, and nasal examination. At the doses tested, no significant dissociative effects were evident using the Side Effects Rating Scale for Dissociative Anaesthetics.
About PMI-100/150 (Intranasal Ketamine)
The paper, "Safety and Efficacy of Intranasal Ketamine for Acute Pain" has just been published in "Acute Pain" the International Journal of Acute Pain Management, Volume 9, Issue 4, Pages 183-236 (December 2007). An abstract of the paper can be viewed online: http://www.sciencedirect.com/science/journal/13660071
The Company is developing PMI-100 and PMI-150, proprietary nasal formulations of ketamine at concentrations of 150 mg/ml, for acute to moderate-to-severe pain. The Company anticipates undertaking additional clinical studies aimed at broadening PMI-150's potential indications. A Phase 3, multicenter study of intranasal ketamine for breakthrough cancer pain is currently under way. Javelin believes that PMI-100/150 are optimized for use as a pain medication and may offer a safe, non-opioid alternative for the treatment of moderate-to-severe pain. Prior randomized, double-blinded, placebo-controlled phase II clinical studies of PMI-150 have demonstrated rapid, statistically significant relief of moderate to severe breakthrough pain due to cancer and other serious medical conditions.
Ketamine, a non-opiate, is an N-methyl-D-aspartate (NMDA) receptor antagonist that has been in clinical use for over 30 years. Since its approval by the FDA, ketamine has been safely used as an anesthetic in tens of thousands of patients. NMDA receptors are located in the central nervous system and play a role in the perception of acute and chronic pain. Ketamine, at lower doses than those approved for anesthetic use, has been reported in the medical literature to be an effective analgesic for post operative settings, nerve injury pain, and pain during medical procedures, such as burn dressing changes.
About Javelin Pharmaceuticals, Inc.
With corporate headquarters in Cambridge, MA, Javelin applies innovative proprietary technologies to develop new drugs and improved formulations of existing drugs to target unmet and underserved medical needs in the pain management market. The Company has three drug candidates in Phase 3 clinical development. One of these Phase 3 drug candidates, Dyloject(TM), is currently under review for Marketing Authorization Application (MAA) approval in Europe. Previous clinical trials have demonstrated its safety and rapid onset of action. For additional information about Javelin, please visit the company's website at http://www.javelinpharmaceuticals.com.
Forward Looking Statement
This news release contains forward-looking statements. Such statements are valid only as of today, and we disclaim any obligation to update this information. These statements are subject to known and unknown risks and uncertainties that may cause actual future experience and results to differ materially from the statements made. These statements are based on our current beliefs and expectations as to such future outcomes. Drug discovery and development involve a high degree of risk. Factors that might cause such a material difference include, among others, uncertainties related to the ability to attract and retain partners for our technologies, the identification of lead compounds, the successful preclinical development thereof, the completion of clinical trials, the FDA review process and other governmental regulation, our ability to obtain working capital, our ability to successfully develop and commercialize drug candidates, and competition from other pharmaceutical companies.
Javelin Pharmaceuticals, Inc.
Rick Pierce, 617-349-4500
VP Investor Relations
Posted: December 2007