South San Francisco, CA --October 27, 2009 (Business Wire)-- Hyperion Therapeutics today announced that the first patient has been enrolled in its pivotal phase III clinical trial of investigational compound HPN-100 (glycerol phenylbutyrate). The 4-week, multi-center, randomized, double-blind, cross-over study is designed to evaluate the non-inferiority of glycerol phenylbutyrate to BUPHENYL® (sodium phenylbutyrate) Tablets and Powder in adults with urea cycle disorders. The primary efficacy measure is blood ammonia, assessed as 24-hour area under the curve on Days 14 and 28 (last day of each treatment period). The study will enroll approximately 44 adults, and all subjects completing the study will be eligible to enter a 12-month, open label safety study. The study is being conducted under a Special Protocol Assessment ("SPA") that was granted earlier this year by the U.S. Food and Drug Administration ("FDA").
About HPN-100 (glycerol phenylbutyrate)
HPN-100 (glycerol phenylbutyrate), an investigational product, is a pre-pro-drug of phenylacetic acid, the active moiety of BUPHENYL®, the only therapy currently FDA-approved as adjunctive therapy for the chronic management of patients with the most prevalent urea cycle disorders: carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), and argininosuccinic acid synthetase (AS) deficiencies. Glycerol phenylbutyrate is administered orally in liquid form. 17.4 mL of glycerol phenylbutyrate (~ 3.5 teaspoons) delivers the same amount of active ingredient as the maximum daily dose of BUPHENYL (forty tablets or 6.67 teaspoons of powder mixed with food or dissolved in liquid). Glycerol phenylbutyrate holds orphan product designation from the FDA for maintenance treatment of patients with enzymes of the urea cycle.
About Urea Cycle Disorders
Urea cycle disorders are inherited, inborn errors of metabolism present in an estimated 1 in 10,000 births in the United States. Patients with urea cycle disorders are deficient in one of the key enzymes that comprise the urea cycle, the body`s primary vehicle for removing ammonia, a potent neurotoxin, from the bloodstream. Onset may occur at any age depending on the severity of the disorder. Left untreated, urea cycle disorders can cause dangerously heightened levels of ammonia in the bloodstream (hyperammonemia) resulting in brain damage, coma, and/or death.
About BUPHENYL (sodium phenylbutyrate) Tablets and Powder
BUPHENYL is indicated as adjunctive therapy in the chronic management of patients with urea cycle disorders involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS). BUPHENYL should not be administered to patients with known hypersensitivity to sodium phenylbutyrate or any component of this preparation. The most common adverse reactions associated with BUPHENYL were amenorrhea dysfunction, decreased appetite, body odor (probably caused by its metabolite phenylacetate) and bad taste or taste aversion. Patients with urea cycle disorders should not take valproic acid, haloperidol, or steroids as these drugs have been reported to increase blood ammonia levels, and probenecid may affect the kidneys` excretion. Use with great care, if at all, in patients with congestive heart failure or severe renal insufficiency, and in clinical states where there is sodium retention with edema. Use caution when administering to patients with hepatic or renal insufficiency or inborn errors of beta oxidation. The safety or efficacy of doses in excess of 20 grams (40 tablets) per day has not been established.