Cytochroma, a clinical-stage specialty pharmaceutical company, has started phase III study of CTAP101 capsules in patients with secondary hyperparathyroidism (SHPT), stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency. This trial is the first of two identical randomized, double-blind, placebo controlled, multi-site studies intended to establish the safety and efficacy of CTAP101 Capsules as a new treatment for SHPT in the targeted population.

The endpoints of both studies, which will be conducted in parallel, include vitamin D status, adverse events, physical and clinical laboratory assessments, and changes in serum calcium, serum phosphorus and plasma intact parathyroid hormone (PTH).

“Secondary hyperparathyroidism develops in CKD patients due to vitamin D insufficiency or declining kidney function,” explained Joel Z Melnick, MD, Cytochroma’s vice president, Clinical Research and Development. “Most CKD patients have insufficient stores of vitamin D due to the abnormal upregulation of CYP24, an enzyme which specifically destroys vitamin D and its metabolites. Many recent studies in CKD patients have demonstrated that over-the-counter and prescription vitamin D supplements cannot reliably raise blood vitamin D prohormone levels or effectively treat SHPT. In contrast, our phase II b trial has demonstrated that CTAP101 Capsules effectively and safely treat both SHPT and the underlying vitamin D insufficiency.”

The ongoing phase III trial will involve 210 patients recruited from approximately 30 sites in the United States (US). These patients will be stratified by CKD stage and randomized in a 2:1 fashion to receive six months of treatment with either CTAP101 Capsules or matching placebo. Dosing with CTAP101 Capsules will start at 30 mcg/day and be titrated, as necessary, to achieve the desired drug concentration in the blood and the targeted reduction in plasma PTH.

“CTAP101 capsules are being developed as a much needed and safer alternative to currently used activated vitamin D hormones,” commented Dr David Bushinsky, Chief of Nephrology at the University of Rochester. “Activated vitamin D hormone therapy is problematic in CKD patients with secondary hyperparathyroidism arising primarily from vitamin D insufficiency since it further stimulates catabolism of the available vitamin D stores and is often associated with hypercalcemia, a side effect linked to vascular calcification.”

The phase III programme will be funded, in part, by committed financings of nearly $CDN 32 million of which the first two stages closed earlier this year. The lead investors in the financings were Covington Fund II (Toronto) and Business Development Bank of Canada (Montreal). Participating investors included the Bombardier Trust (Canada) Funds (Montreal), Caisse de dépôt et placement du Québec (Québec), Comerica Bank (Toronto), GrowthWorks (Toronto), MaRS Investment Accelerator Fund (Toronto), Partners Group (Zug), Roseway Capital Sarl (Luxembourg) and VentureLink Innovation Fund (Toronto).

“Covington is delighted to support the phase III development of CTAP101 Capsules,” stated Lily Lam, VP Investments, Covington and a director of Cytochroma. “Speaking on behalf of all participants in these financings, we view CTAP101 Capsules as a well-advanced and low risk product candidate with high commercial prospects under rapid development by an experienced management team.”

The two identical pivotal phase III trials are covered by a Special Protocol Assessment granted by the US Food and Drug Administration (FDA) on August 30, 2012.

The product, CTAP101 Capsules, is a first-in-class vitamin D prohormone treatment being developed for elevated PTH secretion (SHPT) in CKD patients with vitamin D insufficiency. It has a proprietary modified-release formulation designed to gradually and reliably raise serum total 25-hydroxyvitamin D (prohormone) concentrations to targeted levels (at least 30 ng/mL) while avoiding upregulation of CYP24, a cytochrome P-450 enzyme  that reduces the PTH-lowering potency of current vitamin D supplements.  Activation of the product by the kidney is tightly regulated, preventing excessive elevation of serum calcium and related side effects which encumber vitamin D hormone therapies and promote vascular and renal calcification.

Cytochroma is focused on developing and commercializing proprietary products to treat and prevent the clinical consequences of vitamin D insufficiency and SHPT associated with CKD.