Napo Pharmaceuticals, Inc., which focuses on the development and commercialization of proprietary pharmaceuticals for the global marketplace in collaboration with local partners, today announced that under the Special Protocol Assessment (SPA) process it has obtained agreement with the United States Food and Drug Administration (FDA) for the design of its pivotal study protocol for crofelemer for the treatment of chronic diarrhea in people with HIV/AIDS (CRO-HIV).
The study, also referred to as the ADVENT trial, will be carried out under an FDA Fast Track designation. On Jan. 16, 2007, Napo met with the FDA under the Special Protocol Assessment Process on this adaptive design of its ADVENT trial. On March 14, 2007, Napo announced it had received approval from the principal independent review board (IRB) overseeing the ADVENT trial.
The ADVENT trial -- (Anti-Diarrhea therapy in HIV disease-Emerging treatmeNT concepts) is a randomized, double-blind, parallel-group, placebo- controlled, two-stage, adaptive design study to assess the efficacy and safety of crofelemer at 125mg, 250 mg and 500 mg oral doses twice daily (p.o.b.i.d) for the treatment of HIV-Associated Diarrhea.
The 'adaptive design' of the ADVENT trial -- Adaptive trial design has been advocated by the FDA to improve efficiency of clinical trials. The ADVENT trial will be executed in two stages. Stage I represents a dose selection stage and Stage II, a dose assessment stage. Four dose groups (placebo, 125 mg, 250 mg, and 500 mg) will be assessed in Stage I. When 50 subjects per group complete the initial efficacy dosing period (28 days), an interim analysis will be conducted to select an optimal single dose of crofelemer for Stage II. Stage II will continue until an additional 75 subjects are randomized both to this dose of crofelemer and the placebo, providing for 125 patients on placebo and 125 patients the selected crofelemer dose. The primary study analysis is planned after all subjects complete the 28-day efficacy period. A full study analysis and final study report will be prepared at that time that will form the basis of a subsequent New Drug Application (NDA) filing to FDA. Subjects who complete the efficacy part of the study will be allowed to continue into an open-label, five-month extension. The purpose of the extension is to provide additional safety and tolerability information about crofelemer in longer tem use.
Commenting on this announcement, Lisa Conte, Chief Executive Officer of Napo Pharmaceuticals, said: "The SPA agreement is an important milestone for Napo, allowing us to address and mitigate regulatory uncertainty prior to the completion of our final Phase 3 trial in support of the Company's first NDA filing, targeted for early 2008."
Dr. Scott Harris, Vice President, Clinical Affairs, and Chief Medical Officer, said: "Napo has taken every effort to design and execute a Phase 3 program with the highest possible probability of success, incorporating experience from approximately 1,500 patients studied in clinical trials involving crofelemer. Already, 55 patients have enrolled in a previously conducted Feasibility Study of CRO-HIV. We expect these patients to be immediately eligible for enrolment for the ADVENT study."