Simultaneous control of PTH and CaxP Is sustained over three years of treatment with cinacalcet HCl

Abstract

Background & objectives: Chronic kidney disease (CKD) is commonly complicated by secondary hyperparathyroidism (SHPT), leading to increased risk of morbidity and mortality. SHPT is a progressive disease often requiring long-term therapy to control parathyroid hormone (PTH) and mineral imbalances. Vitamin D sterols and phosphate binders, used as traditional therapies to lower PTH and phosphorus, may provide inadequate long-term control for many dialysis patients. Cinacalcet, by simultaneously lowering PTH, calcium, phosphorus, and calcium-phosphorus levels, may maintain PTH and mineral balance in these individuals. However, as with traditional therapies, long-term data are limited. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENT: Dialysis subjects from at least one of five lead-in studies (double-blind placebo-controlled, including one extension trial) completing up to 52 wk of either cinacalcet or placebo were eligible for this open-label extension study, including an 8-wk dose titration (initiated at 30 mg/d), followed by 24-wk maintenance and up to 132 wk of follow-up. Final efficacy analysis was at week 180.

Results: Three hundred thirty-four of 589 enrolled subjects received cinacalcet from the beginning of the lead-in study. Weekly median PTH values were < or =300 pg/ml (weeks 16 through 180) and median CaxP values were < or =55 mg(2)/dl(2) (weeks 4 through 180). Similar results were exhibited in the 255 subjects who initially received placebo. Among the patients exposed to cinacalcet from the beginning of the lead-in study, 3% of subjects exhibited treatment-related serious adverse events.

Conclusions: Cinacalcet effectively maintained PTH, Ca and P reductions in dialysis subjects for up to 180 wk.

Figures

Figure 1.

Study schema. Subjects entering this study had completed one or more prior lead-in studies: study A (study 20000172), study B (study 20000183), study C (study 20000188), study D (study 20010240), or study E (study 20010141). Studies A, B, and C were each 6-mo randomized, double-blind, placebo-controlled trials comparing cinacalcet therapy with placebo; study E was a 12-mo randomized, double-blind, placebo-controlled trial also comparing cinacalcet with placebo; study D was a 6-mo extension study of subjects who completed study A or study B. Thus, subjects may have received either 26 or 52 wk of treatment with either cinacalcet or placebo before entering this study. The current study consisted of three phases totaling 164 wk: (1) an 8-wk dose-titration phase, beginning at cinacalcet 30 mg p.o. daily, with weekly visits and sequential dose increases to 60, 90, 120, and 180 mg p.o. daily every 2 wk; (2) a 24-wk maintenance phase and visits every 4 wk; and (3) a maximum 132-wk follow-up phase with visits every 12 wk, during which flexible vitamin D therapy was permitted for all subjects. All total, subjects could have received up to a maximum of 216 wk of cinacalcet therapy. RCT, randomized controlled trial.

Figure 2.

Median PTH values recorded at each scheduled visit for subjects who originally received cinacalcet or placebo during lead-in studies. Shaded area is the NKF-KDOQITM–recommended range for serum PTH levels.

Figure 3.

Proportion of patients in original cinacalcet and original placebo groups who achieved ≥30% reduction in PTH from baseline at each 6-mo period. Reductions in PTH values were calculated against the mean PTH value over the 6-mo period; % is incremental. Some scheduled visits were shifted up to a maximum of 2 wk to align with the closest week indicated in the table. N, number of subjects entering period.

Figure 4.

Median Ca×P values recorded at each scheduled visit for subjects who originally received cinacalcet or placebo during lead-in studies. Shaded area is the NKF-KDOQITM–recommended range for Ca×P.

Figure 5.

Proportion of subjects achieving PTH ≤300 pg/ml and Ca×P ≤ 55 mg2/dl2 at each 6-mo period. Reductions in PTH and Ca×P values were calculated against the mean PTH or Ca×P values, respectively, over the 6-mo period. Some scheduled visits were shifted up to a maximum of 2 wk to align with the closest week indicated in the table. N, number of subjects entering period.