A Long-Term, Multicenter Study of the Efficacy and Safety of Paricalcitol in End-Stage Renal Disease

Clin Nephrol. 2001 Oct;56(4):315-23.

Abstract

Background: Paricalcitol is a vitamin D analog approved for the prevention and treatment of secondary hyperparathyroidism associated with chronic renal failure. This study was designed to evaluate the long-term efficacy and safety of paricalcitol. Additional analysis evaluated the effects of paricalcitol in hypocalcemic and hyperphosphatemic subpopulations.

Patients and methods: One hundred sixty-four end-stage renal disease (ESRD) patiesnts on hemodialysis were treated in an open-label, multicenter study lasting up to 13 months in duration. After a baseline or washout period, an initial starting dose of 0.04-0.393 microg/kg was given 2-3 times per week. This dose was adjusted at the discretion of the investigator according to the patient's intact parathyroid hormone level (iPTH), calcium level, and calcium-phosphorus (Ca x P) product. The therapy was intended to reproduce expected clinical use of paricalcitol. Patients represented a wide cross-section of the ESRD population, and were not excluded from the study based on age or underlying disease.

Results: The mean paricalcitol dose level throughout the study was 0.10 microg/kg. The mean iPTH levels (baseline mean 628.3 +/- 27.65 pg/ml) decreased rapidly during the first 4 months of therapy, and reached the designated target range (100-300 pg/ml) by month 5 (mean 295.3 +/- 25.69 pg/ml). A maximum mean decrease in iPTH level of 409 +/- 35.01 pg/ml was seen at month 13. Throughout the course of the study, the mean normalized calcium level was maintained well within the normal range (9.44-9.94 mg/dl). The mean phosphorus level was maintained in an acceptable range throughout the study (5.92-6.53 mg/dl). Mean Ca x P product was maintained between 52 and 65. Mean alkaline phosphatase levels decreased significantly from baseline with a maximum mean decrease of 62 +/- 17.3 U/l observed at month 9. In 34 initially hypocalcemic patients (mean of 7.7 mg/dl) iPTH levels decreased from baseline, on average, by 443 +/- 81.86 pg/ml while mean calcium levels rose by 1.2 +/- 0.23 mg/dl to reach the normal range. In 35 initially hyperphosphatemic patients (mean of 8.0 mg/dl) iPTH levels decreased, on average, by 515 +/- 103.31 pg/ml with an associated mean decrease in phosphorus of 0.57 +/- 0.52 mg/dl. Adverse events that were considered by the investigator to have a possible. probable, or definite relationship to study drug occurred in 26% of patients. Other than expected temporary effects of hypercalcemia and hyperphosphatemia. the only possible trends for causally-related adverse events were for nausea/vomiting and metallic taste.

Conclusions: This long-term study of paricalcitol demonstrates that it rapidly and effectively suppresses iPTH levels in a wide spectrum of ESRD patients and caused no unexpected adverse events.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alkaline Phosphatase / blood
  • Calcium / blood
  • Ergocalciferols / adverse effects
  • Ergocalciferols / therapeutic use*
  • Female
  • Humans
  • Hyperparathyroidism, Secondary / blood
  • Hyperparathyroidism, Secondary / drug therapy*
  • Hyperparathyroidism, Secondary / etiology
  • Hypocalcemia / blood
  • Hypocalcemia / drug therapy*
  • Hypocalcemia / etiology
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / drug therapy*
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Parathyroid Hormone / blood
  • Phosphorus / blood
  • Taste Disorders / chemically induced
  • Time Factors
  • Vomiting / chemically induced

Substances

  • Ergocalciferols
  • Parathyroid Hormone
  • Phosphorus
  • paricalcitol
  • Alkaline Phosphatase
  • Calcium