OPKO Health, Inc. (NYSE: OPK), announced the submission of an Investigational New Drug (IND) Application to the United States (U.S.) Food and Drug Administration (FDA) under which Rayaldee™ will begin clinical evaluation as an adjunctive therapy for the prevention of skeletal-related events (SREs) in patients with bone metastases undergoing anti-resorptive therapy. The initial investigation described in this IND is a phase 1 dose titration study designed to evaluate the safety and tolerability of Rayaldee in patients with breast or prostate cancer that has metastasized to bone who are receiving treatment with zoledronic acid (a bisphosphonate) or denosumab (a RANKL inhibitor). Approximately 24 subjects (12 with each cancer type) will receive Rayaldee at a starting daily dose of 30 µg (1 capsule) for 4 weeks. The dose will escalate in 30 µg increments at 4-week intervals until predetermined biochemical endpoints are reached, at which time the subjects will enter a 12-week maintenance phase. Safety parameters and various markers of bone metabolism, immune function and tumor burden will be monitored at regular intervals. This study is expected to commence later this year and to take approximately 18 months to complete. Following evaluation of this initial study, OPKO plans to conduct subsequent studies investigating the effects of Rayaldee on SREs and other parameters deemed to indicate potential clinical benefits in the targeted population. About Rayaldee™Rayaldee is a first-in-class oral vitamin D prohormone treatment in late-stage clinical development for secondary hyperparathyroidism (SHPT) in patients with stage 3 or 4 chronic kidney disease (CKD) and 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 calcifediol, the active ingredient in Rayaldee, by the kidney is tightly regulated, preventing excessive elevation of serum calcium and related side effects which limit the value of current vitamin D hormone therapies by promoting vascular and renal calcification. Rayaldee is expected to address the approximately 4 million patients in the U.S. and many more elsewhere, with stage 3 or 4 CKD, SHPT and vitamin D insufficiency. About Chronic Kidney Disease CKD is a condition characterized by a progressive decline in kidney function. The kidney is normally responsible for excreting waste and excess water from the body, and for regulating various hormones. CKD is classified in five different stages — mild (stage 1) to severe (stage 5) disease — as measured by the kidney's glomerular filtration rate. According to the National Kidney Foundation, CKD afflicts over 26 million people in the U.S., including more than eight million patients with moderate (stages 3 or 4) and severe (stage 5) forms of CKD. In stage 5 CKD, kidney function is minimal to absent and patients require regular dialysis or a kidney transplant for survival.