Raptor Pharmaceutical Corp. announced it has completed enrolment in its phase III clinical trial of its proprietary delayed-release oral formulation of cysteamine bitartrate (DR Cysteamine) in patients with nephropathic cystinosis (cystinosis).

The pivotal phase III clinical trial is designed as an outpatient study of the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of DR Cysteamine dosed every twelve hours in patients with cystinosis, compared to the current standard of care, immediate-release cysteamine bitartrate, which requires dosing every six hours. Raptor expects over 30 patients to complete the eight-week study protocol. All patients completing the phase III clinical trial have the option of enrolling in a long-term follow-on study where they continue to receive DR Cysteamine twice daily for the extent of the study.

“As defined in our statistical analysis plan, an interim statistical analysis of intra-patient variance after 20 patients had completed the study, led us to determine that our patient enrollment is complete. With enrollment completed, we anticipate that we will be able to meet our goal of reporting top line data from this clinical trial in the first quarter of 2011,” remarked Patrice P. Rioux, MD, PhD, chief medical officer of Raptor. “Patient compliance is paramount to improving therapeutic control and achieving optimal long-term treatment outcome, and we believe twice-daily DR Cysteamine has the potential to be as efficacious as immediate-release cysteamine bitartrate for cystinosis patients, but with a more convenient dosing schedule and potentially improved tolerability.”

The randomized, crossover design of the pivotal phase III clinical trial is a result of discussions with the US Food and Drug Administration (FDA) through which the FDA provided significant guidance on trial protocol design, clinical endpoints, and statistical analyses plans. The primary endpoint of the multi-centre, global clinical trial is the steady-state White Blood Cell (WBC) cystine levels of patients taking DR Cysteamine compared to immediate-release cysteamine bitartrate. Secondary endpoints are the safety and tolerability of DR Cysteamine and the comparability of steady-state PK of DR Cysteamine and immediate-release cysteamine bitartrate.

“DR Cysteamine has the potential to address two critical issues with the current treatment regimen for cystinosis patients, which result in sub-optimal disease control in many of them. I believe this new formulation of cysteamine bitartrate could greatly improve the quality of life and long-term health outcomes of these patients,” said Craig Langman, MD, The Isaac A Abt MD Professor of Kidney Diseases at the Feinberg School of Medicine, Northwestern University, and Lead Investigator in Raptor's phase III clinical trial.

In November 2009, Raptor completed its phase II b clinical trial of DR Cysteamine in cystinosis. DR Cysteamine demonstrated improved tolerability and the potential to reduce total daily dosage and administration frequency compared to immediate-release cysteamine bitartrate. Immediate-release cysteamine bitartrate is the only drug therapy approved for marketing by the FDA and European Medicines Agency (EMA) for this indication. Despite being the standard of care, gastrointestinal side effects and a strict around-the-clock, every 6 hour dosing schedule for immediate-release cysteamine bitartrate create tolerability and compliance issues for cystinosis patients that DR Cysteamine is designed to address.

Nephropathic cystinosis is an inborn metabolic error characterized by the abnormal transport of cystine, an amino acid, out of the lysosomes. Failure to treat nephropathic cystinosis can cause serious health consequences, including renal failure and resultant need for a kidney transplant; growth failure; rickets and fractures; photophobia and blindness. Symptom onset typically occurs within the first year of life, when cystine crystals accumulate in various tissues and organs, including the kidneys, brain, liver, thyroid, pancreas, muscles and eyes.

DR Cysteamine is Raptor's proprietary enteric-coated, microbead oral formulation of cysteamine bitartrate designed to potentially reduce dosing frequency and gastrointestinal side effects associated with immediate-release cysteamine bitartrate, which is approved for sale by the FDA and EMA to treat nephropathic cystinosis, a rare, genetic lysosomal storage disease.

In December 2007, Raptor obtained an exclusive, worldwide license from the University of California, San Diego for the development DR Cysteamine for nephropathic cystinosis and cysteamine for other potential indications including Huntington's Disease, NASH and Batten Disease.

Raptor Pharmaceutical Corp. is dedicated to speeding the delivery of new treatment options to patients by working to improve existing therapeutics through the application of highly specialized drug targeting platforms and formulation expertise and focuses on underserved patient populations where it can have the greatest potential impact.