Clinical trial NCT01896232: Head-to-Head Study of Etelcalcetide (AMG 416) and Cinacalcet
Official title: A Multicenter, Multiple-dose, Two-arm, Active-controlled, Double-blind, Double-dummy Study to Compare the Therapeutic Efficacy and Safety of Oral Doses of Cinacalcet HCl With Intravenous Doses of AMG 416 in Hemodialysis Subjects With Secondary Hyperparathyroidism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Secondary Hyperparathyroidism
Chronic Kidney Disease
Keywords: Secondary Hyperparathyroidism, renal, kidney, kidneys, dialysis, hemodialysis, chronic kidney disease, CKD, SHPT
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2013-07-11
Enrollment: 683
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to demonstrate that treatment with etelcalcetide (AMG 416) is not inferior to treatment with cinacalcet for lowering serum parathyroid hormone (PTH) levels by \> 30% from baseline among patients with chronic kidney disease (CKD) and secondary hyperparathyroidism (SHPT) who require management with hemodialysis.


Eligibility criteria: Inclusion Criteria:

* Eligible subjects must be receiving adequate thrice weekly maintenance hemodialysis with a dialysate calcium concentration ≥ 2.5 mEq/L for at least 3 months prior to screening laboratory assessments
* Subjects must have SHPT as defined by one central laboratory screening predialysis serum PTH value \> 500 pg/mL, measured on separate days within 2 weeks prior to randomization
* Subjects must have one serum cCa value ≥ 8.3 mg/dL obtained before dialysis within 2 weeks of the date of randomization
* Subjects receiving calcium supplements must have no more than a maximum dose change of 50% within 2 weeks before screening laboratory assessments are obtained, and the dose must remain unchanged through randomization

Exclusion Criteria:

* Eligible subjects cannot have received cinacalcet during the 3 months preceding the first screening laboratory assessment
* Other criteria may apply

Primary outcomes:
measure: Percentage of Participants With > 30% Reduction From Baseline in Mean Parathyroid Hormone During the Efficacy Assessment Phase - Non-inferiority Analysis
timeFrame: Baseline and the efficacy assessment phase (EAP; defined as Weeks 20 to 27, inclusive).
Secondary outcomes:
measure: Percentage of Participants With > 50% Reduction From Baseline in Mean PTH During the Efficacy Assessment Phase
timeFrame: Baseline and the efficacy assessment phase (Weeks 20 to 27, inclusive).
measure: Percentage of Participants With > 30% Reduction From Baseline in Mean PTH During the Efficacy Assessment Phase
timeFrame: Baseline and the efficacy assessment phase (Week 20 to Week 27)
measure: Mean Number of Days of Vomiting or Nausea Per Week in the First 8 Weeks
timeFrame: First 8 weeks
measure: Percent Change From Baseline in Mean Corrected Calcium During the Efficacy Assessment Phase
timeFrame: Baseline and the efficacy assessment phase (weeks 20 - 27)
measure: Percentage of Participants With Mean Predialysis Serum Phosphorus ≤ 4.5 mg/dL During the Efficacy Assessment Phase
timeFrame: Efficacy assessment phase (weeks 20 - 27)
measure: Mean Severity of Nausea in the First 8 Weeks
timeFrame: First 8 weeks
measure: Mean Number of Episodes of Vomiting Per Week in the First 8 Weeks
timeFrame: First 8 weeks
Other outcomes:
Locations:
city: Azusa
country: United States
facility: Research Site
state: California
city: Bakersfield
country: United States
facility: Research Site
state: California
city: Bakersfield
country: United States
facility: Research Site
state: California
city: Chula Vista
country: United States
facility: Research Site
state: California
city: Covina
country: United States
facility: Research Site
state: California
city: Granada Hills
country: United States
facility: Research Site
state: California
city: La Mesa
country: United States
facility: Research Site
state: California
city: La Puente
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
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state: California
city: San Diego
country: United States
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state: California
city: San Gabriel
country: United States
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state: California
city: Whittier
country: United States
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state: California
city: Arvada
country: United States
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state: Colorado
city: Aurora
country: United States
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state: Colorado
city: Longmont
country: United States
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state: Colorado
city: Westminster
country: United States
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state: Colorado
city: Orange
country: United States
facility: Research Site
state: Connecticut
city: Pembroke Pines
country: United States
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state: Florida
city: Pinecrest
country: United States
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state: Florida
city: Tampa
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city: Baton Rouge
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state: Louisiana
city: Lafayette
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city: Southgate
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state: Michigan
city: Columbus
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city: Gulfport
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state: Mississippi
city: Sewell
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state: New Jersey
city: Bronx
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city: Great Neck
country: United States
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state: New York
city: Mineola
country: United States
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state: New York
city: Ridgewood
country: United States
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city: Rosedale
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city: Wilmington
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state: North Carolina
city: Cincinnati
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city: Columbus
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city: San Antonio
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city: Portsmouth
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city: Madison
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state: Wisconsin
city: Feldkirch
country: Austria
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city: Linz
country: Austria
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country: Austria
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city: Genk
country: Belgium
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city: Hasselt
country: Belgium
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city: Kortrijk
country: Belgium
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city: Roeselare
country: Belgium
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city: Edmonton
country: Canada
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state: Alberta
city: Saint John
country: Canada
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state: New Brunswick
city: St. Johns
country: Canada
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state: Newfoundland and Labrador
city: Brampton
country: Canada
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state: Ontario
city: Greenfield Park
country: Canada
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state: Quebec
city: Novy Jicin
country: Czechia
facility: Research Site
city: Praha 4 - Nusle
country: Czechia
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city: Praha 6
country: Czechia
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city: Slavkov u Brna
country: Czechia
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city: Trinec
country: Czechia
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city: Usti nad Orlici
country: Czechia
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city: Aalborg
country: Denmark
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city: Fredericia
country: Denmark
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city: Kobenhavn
country: Denmark
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city: Odense
country: Denmark
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city: Roskilde
country: Denmark
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country: Estonia
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country: Estonia
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country: Estonia
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country: France
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country: France
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country: France
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country: France
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country: France
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country: France
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city: Sainte Foy les Lyon
country: France
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city: Aachen
country: Germany
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city: Coburg
country: Germany
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city: Hamburg
country: Germany
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city: Hannover
country: Germany
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city: Magdeburg
country: Germany
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city: Mettmann
country: Germany
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city: Minden
country: Germany
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city: München
country: Germany
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city: Wiesbaden
country: Germany
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city: Zwickau
country: Germany
facility: Research Site
city: Alexandroupoli
country: Greece
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Ioannina
country: Greece
facility: Research Site
city: Larissa
country: Greece
facility: Research Site
city: Nikaia, Piraeus
country: Greece
facility: Research Site
city: Patra
country: Greece
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city: Thessaloniki
country: Greece
facility: Research Site
city: Budapest
country: Hungary
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city: Gyor
country: Hungary
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city: Kaposvar
country: Hungary
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city: Kistarcsa
country: Hungary
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city: Pecs
country: Hungary
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city: Pecs
country: Hungary
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city: Szekesfehervar
country: Hungary
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city: Szigetvar
country: Hungary
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city: Zalaegerszeg
country: Hungary
facility: Research Site
city: Cagliari
country: Italy
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city: Firenze
country: Italy
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city: Genova
country: Italy
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city: Lecco
country: Italy
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city: Lucca
country: Italy
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city: Milano
country: Italy
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city: Pavia
country: Italy
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city: Pisa
country: Italy
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city: Pordenone
country: Italy
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city: San Giovanni Rotondo FG
country: Italy
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city: Riga
country: Latvia
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country: Latvia
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city: Valmiera
country: Latvia
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city: Alytus
country: Lithuania
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city: Kaunas
country: Lithuania
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country: Lithuania
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country: Lithuania
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city: Klaipeda
country: Lithuania
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country: Lithuania
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city: Ukmerge
country: Lithuania
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city: Hamilton
country: New Zealand
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city: Papatoetoe, Auckland
country: New Zealand
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city: Takapuna, Auckland City
country: New Zealand
facility: Research Site
city: Gdansk
country: Poland
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city: Katowice
country: Poland
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city: Poznan
country: Poland
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country: Poland
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country: Poland
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country: Poland
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country: Poland
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country: Poland
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country: Poland
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country: Poland
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city: Almada
country: Portugal
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city: Aveiro
country: Portugal
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city: Estoril
country: Portugal
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city: Forte Da Casa
country: Portugal
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city: Guimarães
country: Portugal
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city: Lisboa
country: Portugal
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city: Santo Tirso
country: Portugal
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city: Setubal
country: Portugal
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city: Vila Franca de Xira
country: Portugal
facility: Research Site
city: Mitishi
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Petrozavodsk
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
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city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
city: Cordoba
country: Spain
facility: Research Site
state: Andalucía
city: Puerto Real
country: Spain
facility: Research Site
state: Andalucía
city: Badalona
country: Spain
facility: Research Site
state: Cataluña
city: Lleida
country: Spain
facility: Research Site
state: Cataluña
city: Torrevieja
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: Badajoz
country: Spain
facility: Research Site
state: Extremadura
city: Pamplona
country: Spain
facility: Research Site
state: Navarra
city: Galdakao
country: Spain
facility: Research Site
state: País Vasco
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Malmö
country: Sweden
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city: Stockholm
country: Sweden
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city: Trollhättan
country: Sweden
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city: Aarau
country: Switzerland
facility: Research Site
city: Bern
country: Switzerland
facility: Research Site
city: Geneva 14
country: Switzerland
facility: Research Site
city: Lausanne
country: Switzerland
facility: Research Site
city: Lausanne
country: Switzerland
facility: Research Site
city: Locarno
country: Switzerland
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city: Zurich
country: Switzerland
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city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
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city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Block GA, Bushinsky DA, Cheng S, Cunningham J, Dehmel B, Drueke TB, Ketteler M, Kewalramani R, Martin KJ, Moe SM, Patel UD, Silver J, Sun Y, Wang H, Chertow GM. Effect of Etelcalcetide vs Cinacalcet on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: A Randomized Clinical Trial. JAMA. 2017 Jan 10;317(2):156-164. doi: 10.1001/jama.2016.19468.
citation: Stollenwerk B, Iannazzo S, Akehurst R, Adena M, Briggs A, Dehmel B, Parfrey P, Belozeroff V. A Decision-Analytic Model to Assess the Cost-Effectiveness of Etelcalcetide vs. Cinacalcet. Pharmacoeconomics. 2018 May;36(5):603-612. doi: 10.1007/s40273-017-0605-2.
citation: Stollenwerk B, Iannazzo S, Cooper K, Belozeroff V. Exploring the potential value of improved care for secondary hyperparathyroidism with a novel calcimimetic therapy. J Med Econ. 2017 Oct;20(10):1110-1115. doi: 10.1080/13696998.2017.1360309. Epub 2017 Aug 14.
citation: Wu B, Melhem M, Subramanian R, Chen P, Jaramilla Sloey B, Fouqueray B, Hock MB, Skiles GL, Chow AT, Lee E. Clinical Pharmacokinetics and Pharmacodynamics of Etelcalcetide, a Novel Calcimimetic for Treatment of Secondary Hyperparathyroidism in Patients With Chronic Kidney Disease on Hemodialysis. J Clin Pharmacol. 2018 Jun;58(6):717-726. doi: 10.1002/jcph.1090. Epub 2018 Mar 13.
citation: Block GA, Chertow GM, Sullivan JT, Deng H, Mather O, Tomlin H, Serenko M. An integrated analysis of safety and tolerability of etelcalcetide in patients receiving hemodialysis with secondary hyperparathyroidism. PLoS One. 2019 Mar 15;14(3):e0213774. doi: 10.1371/journal.pone.0213774. eCollection 2019.
citation: Wolf M, Block GA, Chertow GM, Cooper K, Fouqueray B, Moe SM, Sun Y, Tomlin H, Vervloet M, Oberbauer R. Effects of etelcalcetide on fibroblast growth factor 23 in patients with secondary hyperparathyroidism receiving hemodialysis. Clin Kidney J. 2019 Apr 26;13(1):75-84. doi: 10.1093/ckj/sfz034. eCollection 2020 Feb.