Safety and Efficacy Study of Paricalcitol Versus Calcitriol in the Treatment of Secondary Hyperparathyroidism

A Multi Centre, Open Label, Parallel Group, Randomized Controlled Trial to Compare the Safety and Efficacy of Oral Paricalcitol Versus Oral Calcitriol in the Treatment of Secondary Hyperparathyroidism in Dialysis Patients

The purpose of this study is to determine whether oral paricalcitol is safer and more efficacious compared to oral calcitriol in the treatment of hyperparathyroidism in chronic kidney disease patients undergoing dialysis.

Secondary hyperparathyroidism, a common consequence of chronic kidney disease, results from abnormal regulation of calcium and phosphate homeostasis. The early administration of calcium supplements or vitamin D attenuates the development and progression of hyperparathyroidism, preventing or retarding the emergence of many of the serious complications of chronic kidney disease. However, these vitamin D derivatives also have serious side effects, including hypercalcemia and hyperphosphatemia and, as a result, a high level of the calcium-phosphate product. These adverse outcomes have prompted the development of novel, "nonhypercalcemic" vitamin D analogues. Three of these analogues have recently been marketed for clinical use in patients with chronic kidney disease: 19-nor-1,25-dihydroxyvitamin D2 (paricalcitol), 1 -hydroxyvitamin D2 (doxercalciferol), and 22-oxacalcitriol.

Oral paricalcitol was developed to provide a convenient, alternative therapy, particularly for Peritoneal Dialysis patients in whom regular intravenous administration of paricalcitol is not practical. This study is designed to determine the proportion of patients with 'End stage renal failure' on haemodialysis or peritoneal dialysis and secondary hyperparathyroidism who achieved more than 30% reduction in baseline iPTH concentration at 24 weeks of treatment with Paricalcitol or Calcitriol capsules.

Inclusion Criteria:

• Age at or above 18 years
• End stage renal disease on regular maintenance haemodialysis or peritoneal dialysis for at least 3 months
• iPTH level of 300 pg/ml or greater at baseline
• Written informed consent by subject or guardian
• Female patients will either be post-menopausal for more than 2 years, surgically sterile or if of childbearing age, using double contraception

Exclusion Criteria:

• Baseline calcium value more than 2.87 mmol/L
• Baseline Ca x P of greater than 5.63 mmol2/l2
• Positive for HBsAg or Hepatitis C with raised ALT twice above upper limit of normal or evidence of liver cirrhosis
• Clinically significant gastrointestinal disease
• History of allergic reaction to calcitriol or other vitamin D compounds
• Inability or unwillingness to provide written consent.
• Inability or unwillingness to comply with the requirements of the protocol as determined by the investigator.
• Pregnancy, breastfeeding or use of non-reliable method of contraception.
• Use of medications prohibited prior to randomization such as ketoconazole and other strong P450 3A inhibitors including atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir
• Necessity for calcitonin, biphosphonates, maintenance oral or intravenous glucocorticoid or cinacalcet or other drugs that may affect calcium or bone metabolism.
• Alcohol or substance abuse within 6 months prior to screening
• Other medical condition which, in the investigator's judgement, may be associated with increased risk to the subject or may interfere with study assessments or outcomes.
• Participation in another clinical trial and/or receipt of investigational drugs within 4 weeks prior to screening visit.
• If PD subjects had active peritonitis within one month prior to the screening visit