Critical Therapeutics Completes Phase I Clinical Trial of the R(+) Isomer of Zileuton.

LEXINGTON, Mass. -- Critical Therapeutics, Inc. (Nasdaq: CRTX) today announced the results of its Phase I clinical trial to assess the safety and tolerability of an oral single dose of the R(+) isomer of zileuton in healthy subjects. R(+) zileuton combined in equal proportion with its mirror image isomer, S(-) zileuton, comprise racemic zileuton, which is the pharmaceutical ingredient in ZYFLO CR(TM) (zileuton) extended-release tablets.

The Phase I clinical trial was a randomized, open-label, single dose, single center, two-period crossover trial designed to examine the safety, tolerability, pharmacokinetic and pharmacodynamic profile of the R(+) isomer of zileuton in healthy subjects. Twelve subjects each received two dose levels of the R(+) isomer of zileuton (100 and 300 mg) in a randomized, crossover design. Both dose levels of R(+) zileuton were well tolerated with no serious adverse events or clinical safety concerns reported in this trial.

Pharmacokinetic data obtained for R(+) zileuton, dosed alone to humans for the first time, exhibited dose proportionality and matched historical data obtained for R(+) zileuton following equivalent doses of racemic zileuton in earlier clinical trials. The pharmacokinetic profile of R(+) zileuton obtained in the currently reported trial confirmed that it constitutes about two-thirds of the plasma exposure observed with racemic zileuton and is the more persistent isomer of zileuton. "These pharmacokinetic parameters of R(+) zileuton, together with preclinical data we have generated indicating that it could be a more potent leukotriene synthesis inhibitor, suggest this isomer of zileuton may be a candidate as a next generation leukotriene synthesis inhibitor that could offer reduced dosing and/or a smaller tablet size compared with ZYFLO CR(TM)," said Critical Therapeutics president and chief executive officer, Trevor Phillips, Ph.D.

The planned pharmacodynamic assessment, by measurement of the inhibition of leukotriene B4 (LTB4) production in human whole blood samples, could not be achieved in this trial. This measurement relied on the stimulation of LTB4 production in the human whole blood samples by addition of a calcium ionophore. The stimulation of LTB4 production did not occur and, as a result, the Company was not able to gain any pharmacodynamic data from this trial. In previous in vitro experiments conducted by Critical Therapeutics with human whole blood, R(+) zileuton exhibited potent sub-micromolar inhibition of ionophore-stimulated LTB4 production which was several fold stronger than S(-) zileuton. Future trials would incorporate further consideration of pharmacodynamic potency.

About Critical Therapeutics

Critical Therapeutics, Inc. is developing and commercializing innovative products for respiratory, inflammatory and critical care diseases. The Company owns worldwide rights to two FDA-approved drugs: ZYFLO CR[TM] (zileuton) extended-release tablets and ZYFLO[R] (zileuton tablets). Critical Therapeutics is developing products for acute asthma attacks that lead patients to the emergency room and other urgent care settings. The Company also is developing therapies directed toward the body's inflammatory response. Critical Therapeutics is located in Lexington, Mass. For more information, please visit www.crtx.com.

Forward-Looking Statements 

Any statements in this press release about future expectations, plans and prospects for Critical Therapeutics, Inc., including, without limitation, statements regarding possible therapeutic benefits, market acceptance and future sales of ZYFLO CR; the progress and timing of our drug development programs and related trials, such as our recently completed trial of the R(+) isomer of zileuton; the efficacy of our drug candidates, including the R(+) isomer of zileuton; our strategy, future operations, financial position, future revenues, and projected costs; prospects, plans and objectives of management; and all other statements that are not purely historical in nature, constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Without limiting the foregoing, the words "anticipate," "believe," "could," "estimate," "expect," "intend," "may," "plan," "project," "should," "will," "would" and similar expressions are intended to identify forward-looking statements. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including risks and uncertainties relating to: our ability to successfully market and sell ZYFLO CR, including the success of our co-promotion arrangement with Dey, L.P. (DEY); our ability to transition our management team effectively; our current review of our business strategy and future operations, and the implementation of changes in our strategy and future operations, if any, approved by our Board of Directors; our ability to develop and maintain the necessary sales, marketing, distribution and manufacturing capabilities to commercialize ZYFLO CR; patient, physician and third-party payor acceptance of ZYFLO CR as a safe and effective therapeutic product; adverse side effects experienced by patients taking ZYFLO CR or ZYFLO; our heavy dependence on the commercial success of ZYFLO CR; our ability to maintain regulatory approvals to market and sell ZYFLO CR; the success of our co-promotion arrangement with DEY for Perforomist[TM]; our ability to successfully enter into additional strategic co-promotion, collaboration or licensing transactions on favorable terms, if at all; conducting clinical trials, including difficulties or delays in the completion of patient enrollment, data collection or data analysis; the results of preclinical studies and clinical trials with respect to our products under development and whether such results will be indicative of results obtained in later clinical trials; our ability to obtain the substantial additional funding required to conduct our development and commercialization activities; our dependence on our strategic collaboration with MedImmune, Inc.; and our ability to obtain, maintain and enforce patent and other intellectual property protection for ZYFLO CR, our discoveries and our drug candidates. These and other risks are described in greater detail in the "Risk Factors" section of our most recent quarterly report on Form 10-K and other filings that we make with the Securities and Exchange Commission. If one or more of these factors materialize, or if any underlying assumptions prove incorrect, our actual results, performance or achievements may vary materially from any future results, performance or achievements expressed or implied by these forward-looking statements.

In addition, the statements in this press release reflect our expectations and beliefs as of the date of this release. We anticipate that subsequent events and developments will cause our expectations and beliefs to change. However, while we may elect to update these forward-looking statements publicly at some point in the future, we specifically disclaim any obligation to do so, whether as a result of new information, future events or otherwise. Our forward-looking statements do not reflect the potential impact of any future acquisitions, mergers, dispositions, business development transactions, joint ventures or investments we may make. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this release.

ZYFLO[R] is a registered trademark of Critical Therapeutics, Inc.

ZYFLO CR(TM) is a trademark of Critical Therapeutics, Inc.

Perforomist[TM] is a trademark of Dey, L.P.