Critical Therapeutics on Target to Submit NDA for Zileuton Controlled-Release Tablets in Third Quarter 2006
Tuesday May 2, 8:53 am ET
Company Reaches Agreement on Stability Requirements for Submission of NDA
Results of Pharmacokinetic Studies, Together with Previously Conducted Phase III Pivotal Studies, to Support Submission
LEXINGTON, Mass.--(BUSINESS WIRE)--May 2, 2006--Critical Therapeutics, Inc. (Nasdaq: CRTX - News) today announced that the U.S. Food and Drug Administration (FDA) has accepted the Company's proposal to submit the New Drug Application (NDA) for its controlled-release (CR) formulation of zileuton with six months of primary and accelerated stability data and provide additional stability data during the review period without impacting the action date by the FDA.
"We are pleased with the FDA's decision because it puts us in a position to submit the NDA in August 2006 and launch the zileuton CR in 2007, pending regulatory approval," said President and Chief Executive Officer Paul Rubin, M.D. "The introduction of the CR formulation of zileuton would allow us to offer patients a more convenient twice-daily dosing regimen, which we believe would not only expand our asthma product coverage but should also increase patient compliance compared to the four-times daily regimen for ZYFLO® (zileuton tablets)."
The NDA will be supported by data from two recently completed pharmacokinetic studies and two previously conducted Phase III clinical trials. The pharmacokinetic studies compare the bioavailability of zileuton CR tablets and the asthma drug ZYFLO in healthy volunteers. ZYFLO is Critical Therapeutics' currently marketed four-times daily formulation of zileuton, the only 5-lipoxygenase inhibitor approved by the FDA.
Critical Therapeutics licensed zileuton CR and ZYFLO from a third party in late 2003 and early 2004, respectively. The pharmacokinetic studies were designed to evaluate whether the pharmacokinetic profile of zileuton CR tablets manufactured by Critical Therapeutics when compared with ZYFLO is similar to the pharmacokinetic profile of zileuton CR tablets previously manufactured by the third party when compared with ZYFLO.
Because there is no remaining supply of the previously manufactured zileuton CR, Critical Therapeutics decided, after consultation with the FDA, that it should compare the pharmacokinetics of its zileuton CR tablets to ZYFLO and then make a historical comparison to the data from previously manufactured zileuton CR tablets.
Critical Therapeutics must show relative bioavailability between the two zileuton CR formulations to enable it to bridge to the previous data generated from the original development of zileuton CR, including the results from the previous Phase III clinical trials.
Critical Therapeutics conducted both a single-dose and a multiple-dose pharmacokinetic study. Each study was conducted in a total of 24 evaluable healthy volunteers. Zileuton CR was well tolerated in both studies. The studies were designed to assess the pharmacokinetics of zileuton CR in fed and fasted conditions and to enable a historical comparison of bioavailability to previously manufactured zileuton CR.
The comparison of the results from the Company's recent single-dose study with the historical single-dose study under fed conditions showed the following results:
Ratio of the mean value for the area under the pharmacokinetic curve (AUC) was 72%, with a 90% confidence interval of 62% - 84%; and
Ratio of the mean value for the maximum concentration in the blood (Cmax) was 71%, with a 90% confidence interval of 59% - 84%.
The comparison of the results from the Company's recent multiple-dose study with the historical multiple-dose study were made on the pharmacokinetic profiles achieved at steady state after six days of repeat dosing under fed conditions and showed the following:
Ratio of the mean value for the AUC was 111%, with a 90% confidence interval of 95% - 130%; and
Ratio of the mean value for the Cmax was 86%, with a 90% confidence interval of 73% - 102%.
"We believe that the pharmacokinetic comparison at steady state under fed conditions is key in the assessment of comparability because zileuton CR is being developed as a chronic treatment and zileuton CR was taken with food during the pivotal trials," said Dr. Rubin.
About Zileuton and ZYFLO
Zileuton inhibits 5-lipoxygenase (5-LO), an enzyme that catalyzes the formation of leukotrienes from arachidonic acid. 5-LO is the main enzyme responsible for the production of leukotrienes, a family of inflammatory mediators that can trigger asthma symptoms including inflammation, swelling, bronchoconstriction and mucus secretion.
ZYFLO, the immediate release tablet formulation of zileuton, blocks the formation of leukotrienes. ZYFLO is indicated for the prevention and chronic treatment of asthma in adults and children 12 years of age and older. The recommended dose is one 600 mg tablet four times a day. ZYFLO is not indicated for use in the reversal of bronchospasm in acute asthma attacks, including status asthmaticus. Therapy with ZYFLO can be continued during acute exacerbations of asthma. ZYFLO should be taken regularly, even during symptom-free periods.
Mild to moderate side effects associated with the use of ZYFLO are abdominal pain, upset stomach and nausea. A small percentage of patients treated with ZYFLO show an increased release of a liver enzyme known as ALT. As a result, the level of liver enzymes in patients treated with ZYFLO should be measured by a simple blood test. It is recommended that physicians perform this test before administering ZYFLO and repeat the test on a regular basis while patients are on the medication. ZYFLO is contraindicated in patients with active liver disease or transaminase elevations greater than or equal to three times the upper limit of normal.
Zileuton CR is an investigational drug product not currently approved for marketing.
For full prescribing information for ZYFLO, please visit www.crtx.com/pat_pi.html or call the Company's toll free telephone number 1-866-835-8216 to request medical information.
About Critical Therapeutics
Critical Therapeutics, Inc. is a biopharmaceutical company focused on the discovery, development and commercialization of products for respiratory, inflammatory and critical care diseases. The Company owns worldwide rights to the asthma drug ZYFLO® (zileuton tablets), as well as other formulations of zileuton. ZYFLO is the only 5-lipoxygenase inhibitor approved for marketing by the U.S. Food and Drug Administration. The Company's commercialization efforts for ZYFLO are carried out by its 80-person specialty sales force. Critical Therapeutics also is developing treatments directed toward the severe inflammatory response in acute diseases and conditions that lead to admission to the emergency room or intensive care unit, and acute exacerbations of other chronic diseases that frequently lead to hospitalization. For more information, please visit www.crtx.com. |
