BioWorld International Correspondent
LONDON - After prolonged negotiations, Alizyme plc reached agreement with the FDA under the special protocol assessment for a 1,700-subject pivotal Phase III trial of renzapride in treating constipation-predominant irritable bowel syndrome (IBS).
The $20 million trial will begin in the fourth quarter with subjects being treated over 12 weeks.
"I'm very happy with the design," Richard Palmer, CEO, told BioWorld International. "I am happy to have reached agreement because we are in a new therapeutic area where there are very few products as yet, and so trial design and analysis is a bit of a moving feast."
There has been a big shift in appetite from potential partners now that renzapride is officially a Phase III product, Palmer said. "Agreeing to the trial design under the SPA was a long process, but we have mitigated the risk for partners, and that's why we persevered with it."
Under the SPA, the FDA cannot change its mind about the design, analysis or execution of the trial, unless significant safety issues emerge. Results are due in the first half of 2007.
Symptoms of IBS come and go and are driven by a variety of factors. Evidence of efficacy in any treatment depends on subjective self-assessments, and typically there is a high placebo effect in IBS trials. "Getting at proof of efficacy depends on just what questions you ask," Palmer said.
In the renzapride trial, response will be determined by weekly self-assessment. The primary endpoint will be whether daily doses of the drug, taken either as 4 mg once daily or 2 mg twice daily, are clinically and statistically more effective than placebo in providing overall relief of symptoms.
The trial is testing two doses to have more subjects receiving active treatment and bolster the safety data. "In any indication that is serious but not life threatening, you need a big safety database. This trial will take the number of people treated with renzapride to 2,500," Palmers said. The Cambridge, UK-based company has completed a cardiovascular safety study, also.
Alizyme raised £32.8 million (US$57.1 million) in April to ensure it has funding for the trial and for a Phase III trial of COLAL-PRED in treating ulcerative colitis.
The drug is a formulation of prednisolone that delivers the steroid directly to the colon, avoiding the usual side effects. The company has approval for a Phase III UK trial for the use of COLAL-PRED in maintaining remission from the disease, and is discussing the design of a Phase III European trial for treating active disease.