DANBURY, Conn., Feb. 10 /PRNewswire-FirstCall/ -- Penwest Pharmaceuticals Co. today announced positive results from its Phase IIa trial of nalbuphine ER (PW4142), an extended release tablet that the Company is developing for the treatment of pain. The goal of the trial was to determine the degree and duration of pain relief of two different dose levels of nalbuphine ER.
Nalbuphine ER, a controlled release formulation of nalbuphine hydrochloride that the Company developed using its Geminex(R) dual drug delivery technology, is designed to be taken as a tablet twice daily. This formulation of nalbuphine ER will have plasma kinetics derived from both immediate release and controlled release components.
Nalbuphine hydrochloride is a synthetic opioid agonist-antagonist analgesic of the phenanthrene series. Nalbuphine hydrochloride is currently only available as a sterile solution suitable for subcutaneous, intramuscular, or intravenous injection under the brand name NUBAIN(R) and as a generic. Given the limits of currently available formulations and indications, annual sales of this product are approximately $10 million. The Company expects that nalbuphine ER, if approved, will compete in the moderate to moderately severe pain space with drugs such as Tramadol(R).
The 165-patient Phase IIa trial was a pharmacokinetic-pharmacodynamic (PK-PD) investigation designed to correlate the level of analgesia in patients with the plasma level of the drug. This trial was conducted to determine if there is an exposure-response relationship, as well as the duration of analgesia. Two different doses of nalbuphine ER were evaluated as single doses and compared to placebo.
Patients in the trial underwent third molar extractions, a commonly used clinical pain model for evaluating the acute effectiveness of analgesics. Under the protocol, patients who experienced at least a score of four on the 0-to-10 NPRS pain scale following completion of their dental procedures received blinded study medication (nalbuphine ER or placebo) as a single dose. Pain relief was then evaluated at pre-specified intervals over the 12-hour period following dosing. Blood samples were also collected for 24 hours post- dose to determine plasma concentrations of nalbuphine ER.
Results from this Phase IIa study demonstrated that nalbuphine ER positively reduced pain intensity in a dose-dependent manner over the 12-hour study period. Separation from placebo began at 90 minutes post-dose for the higher strength and at six hours for the lower strength and was maintained at all time points over the remaining 12-hour dosing interval.
Positive results were also observed in longer time to ingestion of rescue medication and the proportion of patients requiring rescue analgesic therapy during the 12-hour study period for both the low and high nalbuphine ER doses when compared to placebo.
Finally, the percent of patients experiencing at least a 50% reduction in pain intensity during the 12-hour study period was higher for the low and high nalbuphine dose groups compared to placebo. No unusual side effects were reported during the 12-hour dosing interval.
Jennifer L. Good, President and Chief Operating Officer of Penwest, said, "We are very pleased with the results of this proof-of-concept study and are looking ahead to the next steps in the development of this product. Clearly, we need to confirm the findings from this Phase IIa study in different pain models, and we are evaluating whether to develop this drug for our own portfolio or to seek a partner for further development and commercialization."
Penwest completed a Phase I study of nalbuphine ER in 2005. In the Phase I study, nalbuphine ER was administered at multiple dose levels in healthy volunteers and showed relative oral bioavailability of approximately 123% when compared to the marketed injection formulation given by mouth, and the plasma levels of nalbuphine ER were sustained over 12 hours.
Penwest Pharmaceuticals
Penwest develops pharmaceutical products based on innovative oral drug delivery technologies. We are focusing our development efforts principally on products that address diseases of the central nervous system. The foundation of our technology platform is TIMERx(R) an extended release delivery system that is adaptable to soluble and insoluble drugs and that is flexible for a variety of controlled release profiles. We have also developed two additional oral drug delivery systems, Geminex(R) and SyncroDose(TM). Geminex is a dual release rate drug delivery system that is designed to provide independent release of an active ingredient or ingredients contained in a drug, and SyncroDose is a drug delivery system that is designed to release the active ingredient of a drug at the desired site and time in the digestive tract.
The matters discussed herein contain forward-looking statements that involve risks and uncertainties, which may cause Penwest's actual results in future periods to be materially different from any future performance suggested herein. For this purpose, any statements contained herein that are not statements of historical fact may be deemed to be forward-looking statements. Without limiting the foregoing, the words, "believes," "anticipates," "plans," "expects," "intends," "potential," and similar expressions are intended to identify forward-looking statements. Important factors that could cause results to differ materially include; dependence on collaborators such as Endo Pharmaceuticals to, among other things, sell products for which the Company receives royalties, file for regulatory approvals, and/or to advance clinical development and commercialization of products; regulatory risks relating to drugs in development such as oxymorphone ER, including the timing and outcome of regulatory action; uncertainty of success of collaborations; the timing of clinical trials and whether the results of clinical trials will warrant further clinical trials, warrant submission of an application for regulatory approval of, or warrant regulatory approval of, the product that is the subject of the trial; actual and potential competition; the need for capital; and other risks as set forth under the caption Certain Factors That May Affect Future Results in Penwest's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 9, 2005, which risk factors are incorporated herein by reference. Penwest disclaims any intention or obligation to update any forward-looking statements.
Contacts: Investors: Media: Diane D'Alessandro Caroline Gentile/Jim Fingeroth (203) 796-3706 Kekst and Company (877) 736-9378 (212) 521-4800
Penwest Pharmaceuticals Co.CONTACT: Investors - Diane D'Alessandro of Penwest Pharmaceuticals Co.,+1-203-796-3706, 1-877-736-9378; or Media - Caroline Gentile or JimFingeroth, both of Kekst and Company, +1-212-521-4800
Web site: http://www.penw.com/
