Otsuka To Proceed With Tolvaptan Trial After FDA SPA Negotiation

Otsuka Pharmaceutical announced that it will proceed with patient enrollment for its Tolvaptan trial after negotiating with the U.S. Food and Drug Administration (FDA) for a Special Protocol Assessment (SPA) on the trial. The FDA has issued a Complete Response Letter for the drug in August 2013, citing the need for more efficacy and safety information.

Tolvaptan is being investigated as a treatment to slow the progression of kidney disease in patients at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD). The drug is thought to inhibit cyst formation in the kidney as well as its proliferation and growth through its mechanism of action as a selective V2 receptor antagonist blocking the effects of vasopressin.

President and CEO William Carson said, “Otsuka is pleased that the FDA has agreed to the design for this study and we are happy to report that the first patient has been enrolled into the trial. This study represents our ongoing commitment to patients with this rare genetic condition to provide them and their physicians with a novel treatment option.”

A Special Protocol Assessment is intended to be the basis of a marketing application for a product. The SPA is established through a written agreement with the FDA on a clinical trial’s design details and planned analysis. The FDA can change an SPA based on agreements with the sponsor if the agency becomes aware of any new public health concerns.

The placebo-controlled, double-blind, multi-center, parallel-group trial will compare the efficacy and safety of tolvaptan in patients with chronic kidney disease between late stage 2 and early stage 4 due to ADPKD. Around 1,300 tolvaptan-naïve adult patients with ADPKD are expected to be enrolled in the trial across 220 sites around the world. The primary endpoint will compare the efficacy of tolvaptan treatment in renal function test eGFR reduction from baseline to post-treatment follow-up against placebo in patients with ADPKD who tolerate tolvaptan during an initial run-in period.

Autosomal dominant polycystic kidney disease is the most common, life-threatening, inherited genetic kidney disorder around the world. ADPKD affects around 120,000 adults in the U.S. and has been designated an orphan condition by the FDA.