Are you Laura C McCary?

Claim your profile

Publications (7)90.7 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Cinacalcet lowers plasma parathyroid hormone (PTH) levels in patients with secondary hyperparathyroidism (sHPT), but the bone histologic response has not been described. This prospective, double-blind, placebo-controlled trial assessed the effects of cinacalcet on bone histology and serum markers of bone metabolism in dialysis patients with sHPT. Patients with intact PTH (iPTH) > or = 300 pg/ml were randomly assigned 2:1 to receive cinacalcet or placebo with concurrent vitamin D and/or phosphate binder therapy. Cinacalcet (30 - 180 mg/day) was used to achieve iPTH levels < or = 200 pg/ml. Bone biopsies were performed before and after one year of treatment. Baseline and end-of-study data were available from 32 patients (19 cinacalcet, 13 placebo). Baseline bone turnover was elevated in 27, reduced in 3 and normal in 2 patients. Serum bone-specific alkaline phosphatase (BSAP) and N-telopeptide (NTx) were elevated. Cinacalcet treatment decreased PTH and diminished activation frequency, bone formation rate/bone surface, and fibrosis surface/bone surface. Adynamic bone was observed in three patients receiving cinacalcet; in two of these, PTH levels were persistently low (< 100 pg/ml). The histomorphometric parameter changes in bone corresponded to PTH, BSAP and NTx reductions. Bone mineralization parameters remained normal. Treatment with cinacalcet lowered PTH and reduced bone turnover and tissue fibrosis among most dialysis patients with biochemical evidence of sHPT.
    Clinical nephrology 04/2008; 69(4):269-78. · 1.29 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: First-generation immunometric assays for "intact" parathyroid hormone (iPTH) also measure large N-terminally truncated PTH fragments, whereas second-generation assays, such as the "bio-intact" PTH (biPTH) assay, measure only full-length biologically active PTH(1-84). This study compared iPTH and biPTH assays during cinacalcet treatment in subjects with secondary HPT receiving dialysis. Four hundred and ten subjects were enrolled in a 26-week randomized, double-blind, placebo-controlled trial of oral cinacalcet (or placebo), 30 to 180 mg once daily, and efficacy was assessed using biPTH and iPTH assays. Compared with control treatment, cinacalcet improved the management of secondary HPT. Both biPTH and iPTH decreased by 38%+/- 3% during weeks 13 to 26 in the cinacalcet group; biPTH increased by 23%+/- 4% and iPTH increased by 9.5%+/- 3% in the control group (P < 0.001). Fifty-six percent of cinacalcet subjects and 10% of control subjects had a > or = 30% reduction in biPTH, and 61% and 11%, respectively, had a > or = 30% reduction in iPTH. Significant correlations between biPTH and iPTH levels were observed throughout the study. Both assays correlated similarly with bone-specific alkaline phosphatase levels. The ratio of biPTH to iPTH was maintained at 56% +/- 1% after treatment in both treatment groups. Increasing serum calcium levels were associated with a decreasing ratio of biPTH to (iPTH-biPTH). These data show that PTH can be monitored with either iPTH or biPTH assays during therapy with cinacalcet, and that cinacalcet therapy does not exert a major influence on the ratio between PTH(1-84) and large, N-terminally truncated PTH fragments.
    Kidney International 10/2005; 68(3):1236-43. · 8.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Secondary hyperparathyroidism develops early in patients with chronic kidney disease (CKD). Clinical guidelines from the National Kidney Foundation-Kidney/Disease Outcomes Quality Initiative emphasize the need to control parathyroid hormone (PTH), calcium, and phosphorus levels in patients with CKD not receiving dialysis to reduce poor outcomes. This phase 2 study evaluated the effects of the oral calcimimetic cinacalcet hydrochloride in patients with CKD not on dialysis therapy. A randomized, double-blind, placebo-controlled, 18-week study enrolled adults with an estimated glomerular filtration rate of 15 to 50 mL/min/1.73 m2 (0.25 to 0.83 mL/s/1.73 m2) and an intact PTH (iPTH) level greater than 130 pg/mL (ng/L). Cinacalcet (or placebo) was titrated from 30 to 180 mg once daily to obtain a 30% or greater reduction in iPTH levels from baseline. Baseline mean iPTH levels were 243 pg/mL (ng/L) in the cinacalcet group (n = 27) and 236 pg/mL (ng/L) in the control group (n = 27). At baseline, 28% of subjects were being administered vitamin D sterols and 43% were being administered phosphate binders or calcium supplements. The addition of cinacalcet significantly decreased iPTH concentrations compared with controls during the efficacy-assessment phase: 56% versus 19% of subjects achieved a 30% or greater reduction in iPTH levels (P = 0.006), and mean iPTH levels decreased by 32% in the cinacalcet group, but increased by 6% in the control group (P < 0.001). Mean serum calcium and phosphorus levels remained within normal range throughout the study. Cinacalcet generally was well tolerated; the most frequent adverse events were gastrointestinal. This preliminary study provides evidence that cinacalcet is efficacious for the treatment of secondary hyperparathyroidism in subjects with CKD not receiving dialysis.
    American Journal of Kidney Diseases 07/2005; 46(1):58-67. · 5.29 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (NKF-K/DOQItrade mark) has established guidelines for treatment of secondary hyperparathyroidism (HPT). The ability of cinacalcet HCl (Sensipartrade mark) treatment to improve achievement of target levels of parathyroid hormone (PTH), calcium, phosphorus, and calcium-phosphorus product (Ca x P) was investigated in subjects on dialysis with secondary HPT. Data were combined from three placebo-controlled, double-blind, 26-week studies with similar design that randomized 1136 subjects on dialysis to receive traditional therapy plus cinacalcet or placebo. Oral cinacalcet was titrated from 30 to 180 mg/day. Achievement of K/DOQI goals was determined for each treatment group overall and for subgroups defined by baseline intact PTH (iPTH) and Ca x P levels. Cinacalcet-treated subjects were more likely to achieve a mean iPTH </=300 pg/mL (31.8 pmol/L) than were control subjects on traditional therapy (56% vs. 10%, P < 0.001). Cinacalcet-treated subjects were more likely to achieve concentrations of serum calcium within 8.4 to 9.5 mg/dL (2.10-2.37 mmol/L) and serum phosphorus within 3.5 to 5.5 mg/dL (1.13-1.78 mmol/L) than were control subjects (49% vs. 24% and 46% vs. 33%, P < 0.001 for each). Cinacalcet also improved achievement of Ca x P < 55 mg(2)/dL(2) (4.44 mmol(2)/L(2)) and concurrent achievement of Ca x P < 55 mg(2)/dL(2) (4.44 mmol(2)/L(2)) and iPTH </=300 pg/mL (31.8 pmol/L) (65% vs. 36% and 41% vs. 6%, P < 0.001 for each). In subjects on dialysis with secondary HPT, cinacalcet facilitates achievement of the K/DOQI-recommended targets for PTH, calcium, phosphorus, and Ca x P.
    Kidney International 03/2005; 67(2):760-71. · 8.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Treatment of secondary hyperparathyroidism with vitamin D and calcium in patients receiving dialysis is often complicated by hypercalcemia and hyperphosphatemia, which may contribute to cardiovascular disease and adverse clinical outcomes. Calcimimetics target the calcium-sensing receptor and lower parathyroid hormone levels without increasing calcium and phosphorus levels. We report the results of two identical randomized, double-blind, placebo-controlled trials evaluating the safety and effectiveness of the calcimimetic agent cinacalcet hydrochloride. Patients who were receiving hemodialysis and who had inadequately controlled secondary hyperparathyroidism despite standard treatment were randomly assigned to receive cinacalcet (371 patients) or placebo (370 patients) for 26 weeks. Once-daily doses were increased from 30 mg to 180 mg to achieve intact parathyroid hormone levels of 250 pg per milliliter or less. The primary end point was the percentage of patients with values in this range during a 14-week efficacy-assessment phase. Forty-three percent of the cinacalcet group reached the primary end point, as compared with 5 percent of the placebo group (P<0.001). Overall, mean parathyroid hormone values decreased 43 percent in those receiving cinacalcet but increased 9 percent in the placebo group (P<0.001). The serum calcium-phosphorus product declined by 15 percent in the cinacalcet group and remained unchanged in the placebo group (P<0.001). Cinacalcet effectively reduced parathyroid hormone levels independently of disease severity or changes in vitamin D sterol dose. Cinacalcet lowers parathyroid hormone levels and improves calcium-phosphorus homeostasis in patients receiving hemodialysis who have uncontrolled secondary hyperparathyroidism.
    New England Journal of Medicine 04/2004; 350(15):1516-25. · 51.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Calcimimetics increase the sensitivity of the calcium-sensing receptor (CaR) to circulating serum calcium, reducing the secretion of PTH and the serum calcium concentration. We evaluated the calcimimetic cinacalcet, a novel therapy for the management of primary hyperparathyroidism. In this randomized, double-blind, dose-finding study, patients (n = 22) with primary hyperparathyroidism were given cinacalcet (30, 40, or 50 mg) or placebo twice daily for 15 d and observed for an additional 7 d. Serum calcium, plasma PTH, and 24-h and fasting urine calcium were measured. Baseline mean serum calcium was 10.6 mg/dl for the combined cinacalcet-treated patients (normal range, 8.4-10.3 mg/dl), compared with 10.4 mg/dl for the placebo group. Mean PTH at baseline was 102 pg/ml (normal range, 10-65 pg/ml) for the combined cinacalcet-treated patients, compared with 100 pg/ml in the placebo group. Serum calcium normalized after the second dose on d 1 and remained normal through d 15 in all cinacalcet dose groups. Maximum decreases in PTH of over 50% occurred 2-4 h after dosing in all cinacalcet-treated groups. The fasting and 24-h urine calcium to creatinine ratios were similar in the cinacalcet and placebo groups. This study demonstrates that cinacalcet safely normalized serum calcium and lowered PTH concentrations without increasing urinary calcium excretion in the study subjects, indicating the potential benefit of cinacalcet as a medical treatment for primary hyperparathyroidism.
    Journal of Clinical Endocrinology &amp Metabolism 01/2004; 88(12):5644-9. · 6.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Current treatment of secondary hyperparathyroidism in chronic kidney failure with calcium and active vitamin D is potentially limited by hypercalcemia and hyperphosphatemia. AMG 073 represents a new class of compounds for the treatment of hyperparathyroidism known as calcimimetics, which reduce parathyroid hormone (PTH) synthesis and secretion by increasing the sensitivity of the parathyroid calcium-sensing receptor (CaR) to extracellular calcium. The current study evaluates the efficacy and safety of AMG 073 when added to conventional treatment of secondary hyperparathyroidism in end-stage renal disease (ESRD). Seventy-one hemodialysis patients with uncontrolled secondary hyperparathyroidism, despite standard therapy with calcium, phosphate binders, and active vitamin D sterols, were treated in this 18-wk, dose-titration study with single daily oral doses of AMG 073/placebo up to 100 mg. Changes in plasma PTH, serum calcium, serum phosphorus, and calcium x phosphorus levels were compared between AMG 073 and placebo groups. Mean PTH decreased by 33% in the AMG 073 patients compared with an increase of 3% in placebo patients (P = 0.001). A significantly greater proportion of AMG 073 patients (44%) had a mean PTH < or = 250 pg/ml compared with placebo patients (20%; P = 0.029). Also, a significantly greater proportion of AMG 073 patients (53%) had a decrease in PTH > or =30% compared with placebo patients (23%; P = 0.009). Calcium x phosphorus levels decreased by 7.9% in AMG 073 patients compared with an increase of 11.3% in placebo patients (P = 0.013). Adverse event rates were low and mostly mild to moderate in severity; however, the incidence of vomiting was higher in AMG 073 patients. In this study, the calcimimetic AMG 073 at doses up to 100 mg for 18 wk provided a safe and effective means to attain significant reductions in PTH and calcium x phosphorus levels in ESRD patients. AMG 073 represents a novel and promising therapy to improve the management of secondary hyperparathyroidism.
    Journal of the American Society of Nephrology 04/2003; 14(3):575-83. · 8.99 Impact Factor