Hospital Pharmacy - November 2017 - 670

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Comparative Efficacy
Indication: Secondary Hyperparathyroidism in
Patients With CKD Receiving Hemodialysis
Guidelines
Guideline: Hyperphosphatemia in CKD: Management of
hyperphosphatemia in patients with stage 4 or 5 CKD
(National Institute for Health and Care Excellence [NICE]
clinical guideline 157)
Reference: NICE14
Comments: NICE guidelines recommend dietary management and phosphate binders (eg, cinacalcet) for management of hyperphosphatemia in patients with CKD to
reduce the risk of hyperparathyroidism. Etelcalcetide was
not available at the time this guideline was developed. The
Kidney Disease: Improving Global Outcomes (KDIGO)
Chronic Kidney Disease-Mineral and Bone Disorder Work
Group made similar recommendations in 2009.15
Studies
Drug: Etelcalcetide vs Placebo
Reference: Block GA, et al, 2017 (Food and Drug
Administration [FDA] Study 1)1,16
Study Design: Phase 3, randomized, double-blind, placebo-controlled, multicenter, multinational study
Study Funding: Amgen, Inc
Patients: 508 patients with CKD and secondary hyperparathyroidism (PTH greater than 400 pg/mL) receiving
hemodialysis 3 times per week. Patients were taking stable doses of calcium supplements or phosphate binders
and calcitriol or active vitamin D analogs, and had albumin-corrected serum calcium levels of 8.3 mg/dL or
higher. Mean age was 58 years, 57% were men, 69% were
white, 28% were black, 2% were Asian, and 13% were
Hispanic. Mean baseline PTH level was 834.2 pg/mL,
mean baseline corrected serum calcium was 9.6 mg/dL,
and average duration of hemodialysis prior to study entry
was 5.5 years. Sixty-six percent of patients had a mean
screening PTH level greater than or equal to 600 pg/mL,
74% were receiving vitamin D sterols, and 84% were
receiving phosphate binders.
Intervention: Patients were randomized 1:1 to treatment
with etelcalcetide or placebo for 26 weeks. The starting
dose of etelcalcetide was 5 mg 3 times per week administered at the end of hemodialysis. The etelcalcetide dose
was titrated every 4 weeks until week 17 to a maximum
dose of 15 mg 3 times per week to a target PTH level of
less than or equal to 300 pg/mL. Etelcalcetide was held
temporarily if 2 consecutive PTH measurements were
less than 100 pg/mL. The dose of etelcalcetide was not
increased if PTH levels were less than or equal to 300 pg/
mL, corrected serum calcium was less than 8.3 mg/dL,
symptomatic hypocalcemia occurred, or the investigator
judged that no dose increase was needed.

Hospital Pharmacy 52(10)
Results:
Primary End Point(s)
** Proportion of patients with a greater than 30% reduction in PTH levels from baseline to the efficacy assessment phase (mean PTH levels for weeks 20 through
27, inclusive) was 77% with etelcalcetide and 11%
with placebo (P < .001); the number needed to treat
(NNT) for this end point is 1.5.
Secondary End Point(s)
** Proportion of patients with a mean PTH of 300 pg/
mL or lower was 52% with etelcalcetide and 6% with
placebo (P < .001).
** Percent change from baseline in PTH was −49.4%
with etelcalcetide and 14.9% with placebo (P < .001).
** Percent change from baseline in corrected serum calcium was −7% with etelcalcetide and 0.9% with placebo (P < .001).
** Percent change from baseline in phosphate levels was
−8.8% with etelcalcetide and −3.6% with placebo (P
= .08).
Comments: This study was conducted in the United
States, Canada, Europe, Israel, Russia, and Australia.
Limitations: This study demonstrated biochemical control
of secondary hyperparathyroidism compared with placebo
but was not designed to assess the effects of etelcalcetide on
bone architecture or strength, or the likelihood of fracture.
The study was not designed to determine whether etelcalcetide therapy could alter vascular calcification, cardiovascular
structure or function, cardiovascular events, or mortality.
Reference: Block GA, et al, 2017 (FDA Study 2)1,16
Study Design: Phase 3, randomized, double-blind, placebo-controlled, multicenter, multinational study
Study Funding: Amgen, Inc
Patients: 515 patients with CKD and secondary hyperparathyroidism (PTH greater than 400 pg/mL) receiving hemodialysis 3 times per week. Patients were taking stable doses
of calcium supplements or phosphate binders and calcitriol
or active vitamin D analogs, and had albumin-corrected
serum calcium levels of 8.3 mg/dL or higher. Mean age was
59 years, 64% were men, 65% were white, 28% were black,
4% were Asian, and 13% were Hispanic. Mean baseline
PTH level was 848.4 pg/mL, mean baseline corrected serum
calcium was 9.7 mg/dL, and average duration of hemodialysis prior to study entry was 5.4 years. Sixty-seven percent of
patients had a mean screening PTH level greater than or
equal to 600 pg/mL, 62% were receiving vitamin D sterols,
and 81% were receiving phosphate binders.
Intervention: Same as FDA Study 1.
Results:
Primary End Point(s)
** Proportion of patients with a greater than 30% reduction
in PTH levels from baseline to the efficacy assessment

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