Penwest says phase 2a trial shows PW2132 in chronic heart failure patients more effective than Demadex

By E. Janene Geiss

Philadelphia, Dec. 20 - Penwest Pharmaceuticals Co. announced positive results from its phase 2a trial of PW2132, torsemide extended release, a product that the company is developing for chronic management of edema resulting from congestive heart failure.

Torsemide ER, a controlled-release formulation of torsemide that was developed using Penwest's Geminex dual drug-delivery technology, is designed to be taken as a tablet once daily. It provides extended release of the drug during the waking hours when congestive heart failure patients need protection from absorbing salt in the diet, according to a company news release.

Torsemide is currently given as an immediate release oral tablet.

Congestive heart failure is a major cardiovascular disease in the United States affecting 5 million to 7 million patients annually according to the American Heart Association's 2004 statistics on heart disease, the company said.

The class of products to which torsemide belongs - loop diuretics - remains a key part of the clinical management of chronic heart failure, officials said.

The 37-patient study was an open-label, single-center study using a dose-escalation trial design studying the safety, pharmacokinetics and pharmacodynamics of single dose torsemide ER tablets in patients with class II or class III chronic heart failure.

Patients were placed on a sodium-restricted diet for three days prior to dosing. The study also included a comparator arm of Demadex 200 mg, which is the branded immediate release version of torsemide.

The goal of the study was to investigate the total 24-hour urinary sodium excretion, as well as the rate of sodium excretion over the 24-hour period, officials said.

Administration of torsemide ER 100 mg resulted in a total 24-hour urinary sodium excretion comparable to Demadex 200 mg, officials said.

The total sodium excretion of torsemide ER was accomplished at a more sustained and slower rate over the course of the day using half the amount of drug than is in the Demadex formulation, officials said.

Chronically treated chronic heart failure patients typically need to excrete between 150 mEq and 200 mEq of sodium per day to prevent water retention weight gain that can eventually lead to cardiac decompensation, officials said.

The current formulations of loop diuretics have short periods of action in which most of the sodium excretion takes place. These short durations can both leave the patient unprotected for long periods of time during the day, when sodium retention is occurring with food intake, and create the potential for large urinary volume diuresis after drug ingestion, resulting in unpleasant side effects that can affect compliance, officials said.

"Although the study was conducted in the artificial environment of a regulated food intake of a sodium-restricted diet, we are encouraged that the data supports the conclusion that torsemide can be formulated and administered once daily in a manner that can result in a longer duration of action than that provided by currently marketed brands of the drug," Thomas Sciascia, Penwest's chief medical officer, said in the release.

As previously reported, Penwest said it has completed phase 1 studies on this compound to optimize the formulation, met with the U.S. Food and Drug Administration to confirm the scope of the development program and filed initial patent applications.

Penwest said it is filing additional patent applications based on the clinical data from this trial. The company is currently evaluating the next phase of the development program and its commercialization options for this product.

Penwest, based in Danbury, Conn., develops pharmaceutical products based on innovative oral drug delivery technologies.

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