BioWorld International Correspondent

Ipsat Therapies Oy obtained positive data from a Phase IIb clinical trial of its adjunctive penicillin antibiotic therapy P1A, a recombinant beta lactamase enzyme intended to minimize disruption of the normal bacterial flora of the large intestine caused by the presence of unabsorbed drug. The drug candidate attained its two primary endpoints in a placebo-controlled, double-blind trial.

The molecule is administered orally in pellet form, in conjunction with an antibiotic. It mops up residual antibiotic that is not absorbed across the wall of the small intestine, which otherwise would alter the microbial composition of the colon. P1A also can be administered along with intravenously delivered antibiotics, as the latter also can drain into the colon via enterohepatic circulation, biliary excretion or diffusion.

The study found that patients receiving ampicillin plus P1A (n=54) exhibited a smaller alteration in their total gut flora composition compared with those receiving ampicillin plus placebo (n=58).

That was assessed by measuring changes from baseline in each patient's similarity index, which uses denaturing gradient gel electrophoresis to capture a molecular signature of the total microbial community present, based on the population of 16s rRNA gene sequences obtained from stool samples.

Those in the control arm exhibited a 44.5 percent decline in their similarity index after treatment, as compared with a decline of 27.2 percent among those in the treatment group (p<0.001).

"The clinical benefit of that endpoint will be prevention of colonization of [antibiotic-] resistant bacteria," Ipsat CEO Nora Kaarela told BioWorld International. "This is an indirect way of looking at the effect of P1A in degrading the antibiotic."

The data, she said, are in an agreement with those obtained from a previous study involving healthy volunteers.

Those who received P1A but not ampicillin exhibited a 25 percent decline in their similarity index, a change, Kaarela said, that is most likely due to the change of diet associated with hospitalization.

The recent study also found that P1A slowed the emergence of ampicillin-resistant coliforms. Just 12.7 percent of coliform isolates taken from the drug treatment group were ampicillin-resistant, whereas 40.2 percent of coliform samples from the control group were resistant (p< 0.001).

Helsinki, Finland-based Ipsat plans to move P1A into a larger Phase IIb trial next year, which will examine its protective effect in patients receiving piperacillin in combination with the beta-lactamase inhibitor tazobactam. (The latter is deployed in order to counter the effects of pathogenic bacteria producing their own beta-lactamase in response to the presence of antibiotic in the target tissue.)

"The next trial will be looking at prevention of secondary infections and antibiotic-associated diarrhea," Kaarela said. "We will need to demonstrate a reduction in secondary infection and antibiotic-associated diarrhea for the FDA to allow this product to be given prophylactically to patients."

The company has chosen the piperacillin/tazobactam combination therapy as it is the most widely used intravenous hospital antibiotic.

"It is associated with relatively high levels of secondary infections," Kaarela said. Ipsat aims to find a partner for P1A before beginning a Phase III clinical trial.

The company closed its last funding round in December 2005, when it raised a total of €9 million (US$13 million). It is seeking another €15 million at present, and hopes to close the round next spring, Kaarela said.