Logical hoping for results patients can stomach on Phase IIb study of analgesic

NATURE study will explore use of prodrug compound LT-NS001 compared to Naprosyn

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WALTHAM, Mass.—Biotech company Logical Therapeutics Inc., announced April 26 the initiation of a Phase IIb clinical study to evaluate the gastrointestinal (GI) safety of its investigational drug LT-NS001 (naproxen etemesil). The study will compare the cumulative rate of gastric ulcers vs. Naprosyn after 12 weeks of treatment.  

The company says that "LT-NS001 is the most advanced compound in Logical's portfolio of patented Bio-activated Prodrugs, which are being developed to improve the GI safety and tolerability of non-steroidal anti-inflammatory drugs (NSAIDs)."

LT-NS001 is pharmacologically inactive as an NSAID in the GI tract, Logical reports, but once absorbed into the bloodstream, it is converted rapidly and completely into the well-known NSAID naproxen. Previous studies have indicated that LT-NS001 may provide a significant decrease—a 79 percent decrease, in fact, in the incidence of gastric ulcers in subjects after just 7.5 days, as compared to Naprosyn.

In this study, dubbed NATURE (Naproxen etemesil for Arthritis Treatment and Ulcer Reduction Evaluation) the clinical research uses a double-blind, double-dummy, 12-week design to explore the used of LT-NS001 vs. Naprosyn in patients aged 45 to 80 years with osteoarthritis of the knee that requires ongoing NSAID therapy.  

The study is expected to complete enrollment in the fourth quarter of 2010 with 534 patients in the United States and United Kingdom. Patients will be randomly assigned to either LT-NS001 or Naprosyn and will undergo endoscopies at months one, two and three. The primary endpoint is the cumulative incidence of subjects with gastric ulcers in each arm.

In addition to GI safety, injury and tolerability, the study will assess the efficacy of LT-NS001, through the use of the WOMAC functional score, stiffness score and total score for the index knee joint. This evaluation of osteoarthritis pain is designed to confirm the efficacy of LT-NS001, as compared to a therapeutically equivalent dose of naproxen during 12 weeks of dosing, and may be particularly useful for prescribing physicians who are familiar with the use of naproxen.

"Following the success of our proof-of-concept study of LT-NS001 vs. naproxen, the opportunity to demonstrate that our Bio-activated Prodrug may provide a considerable GI safety improvement over traditional naproxen in patients using NSAIDs chronically is quite compelling," says Peter A. Lankau, CEO of Logical Therapeutics. "We believe the NATURE study will confirm the improved GI safety profile of LT-NS001 and will be predictive of the pivotal endpoints as defined by the FDA. It will bring us one step closer to fulfilling the unmet medical need for a single-entity NSAID with a significantly improved GI safety profile."
LT-NS001 is the first in a new class of Bio-activated Prodrugs being developed for the treatment of chronic inflammatory conditions, such as osteoarthritis and rheumatoid arthritis. Prodrugs are compounds that are inactive until enzymes in the body activate them.

Lankau notes that despite the wide availability of gastro-protective agents such as proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2), serious NSAID-induced GI complications—including hemorrhage and perforation—persist and are directly responsible for approximately 20,000 deaths in the United States each year. Furthermore, the chronic administration of PPI's has been associated with serious side effects such as interference with anti-platelet treatments, increased susceptibility to infections and increased risk of bone fracture.  

Logical sees LT-NS001 as a promising path toward improved GI safety with analegesic use, without the need for concomitant alkalinizing agents and their associated risks.

Also, the company notes, the use of NSAIDs is also associated with serious cardiovascular risks, including an increased risk of heart attacks and strokes.

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