OPKO Health reported interim results from an ongoing Phase IV clinical trial comparing Rayaldee with three common treatment regimens for secondary hyperparathyroidism (SHPT) in adult patients with stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency. In this Phase IV study, approximately 80 patients from multiple U.S. clinics will be treated for 2 months in a randomized, open-label fashion with Rayaldee, high-dose cholecalciferol, immediate-release calcifediol, or a combination of paricalcitol and low-dose cholecalciferol. To date, 67 subjects have been enrolled and 62 have completed treatment.
The interim results from all subjects undergoing or completing treatment indicate that a daily dose of 60 mcg of Rayaldee is the only one of the four treatment regimens tested that reliably raises serum total 25-hydroxyvitamin D to the range of 50 to 100 ng/mL, a level required to effectively suppress elevated plasma intact parathyroid hormone (iPTH) in CKD patients (Ennis et at 2016, Strugnell et al 2019). The mean iPTH reduction observed so far with Rayaldee has exceeded 25% from pre-treatment baseline. Cholecalciferol, at a dose of 300,000 international units (IU) per month, and immediate-release calcifediol, at a dose of 265 mcg/month as approved in Europe, have raised mean serum 25-hydroxyvitamin D levels to just over 30 ng/mL and reduced mean plasma iPTH by less than 10%. The inability of cholecalciferol to raise serum 25-hydroxyvitamin D to the desired target range appears to be due to the higher body weights seen in CKD patients.
The combination of paricalcitol (1 mcg per day escalating to 2 mcg per day) and cholecalciferol (800 IU per day) has had no effect on serum 25-hydroxyvitamin D, but has lowered plasma iPTH to approximately the same extent as Rayaldee. Vitamin D receptor activators, such as paricalcitol, can effectively suppress iPTH without increasing serum 25-hydroxyvitamin D, but are no longer suggested for routine use in patients with stage 3 or 4 CKD according to the Kidney Disease Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline Update for CKD-Mineral and Bone Disorder (CKD-MBD). Final results from the ongoing Phase IV trial are expected in the second half of 2020.