Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01896232




Registration number
NCT01896232
Ethics application status
Date submitted
8/07/2013
Date registered
11/07/2013
Date last updated
18/07/2019

Titles & IDs
Public title
Head-to-Head Study of Etelcalcetide (AMG 416) and Cinacalcet
Scientific 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
Secondary ID [1] 0 0
2013-000192-33
Secondary ID [2] 0 0
20120360
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Secondary Hyperparathyroidism 0 0
Chronic Kidney Disease 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Metabolic and Endocrine 0 0 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Etelcalcetide
Treatment: Drugs - Cinacalcet
Treatment: Drugs - Oral Placebo
Treatment: Drugs - Intravenous Placebo

Active Comparator: Cinacalcet - Participants were randomized to receive oral cinacalcet once daily and placebo intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks. The starting dose of cinacalcet was 30 mg daily and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH = 300 pg/mL but no lower than 100 pg/mL while maintaining corrected calcium (cCa) = 8.3 mg/dL.

Experimental: Etelcalcetide - Participants were randomized to receive etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session TIW, and daily oral doses of placebo tablets for 26 weeks. The starting dose of etelcalcetide was 5 mg, and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH = 300 pg/mL but no lower than 100 pg/mL while maintaining cCa = 8.3 mg/dL.


Treatment: Drugs: Etelcalcetide
Administered intravenously three times per week. The starting dose was 5 mg, titrated up to 15 mg based on serum PTH and corrected calcium levels.

Treatment: Drugs: Cinacalcet
Cinacalcet was administered orally once a day. The starting dose was 30 mg daily, titrated up to 180 mg daily based on serum PTH and corrected calcium levels.

Treatment: Drugs: Oral Placebo
Administered orally once a day.

Treatment: Drugs: Intravenous Placebo
Administered intravenously (IV) three times per week.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With > 30% Reduction From Baseline in Mean Parathyroid Hormone During the Efficacy Assessment Phase - Non-inferiority Analysis
Timepoint [1] 0 0
Baseline and the efficacy assessment phase (EAP; defined as Weeks 20 to 27, inclusive).
Secondary outcome [1] 0 0
Percentage of Participants With > 50% Reduction From Baseline in Mean PTH During the Efficacy Assessment Phase
Timepoint [1] 0 0
Baseline and the efficacy assessment phase (Weeks 20 to 27, inclusive).
Secondary outcome [2] 0 0
Percentage of Participants With > 30% Reduction From Baseline in Mean PTH During the Efficacy Assessment Phase
Timepoint [2] 0 0
Baseline and the efficacy assessment phase (Week 20 to Week 27)
Secondary outcome [3] 0 0
Mean Number of Days of Vomiting or Nausea Per Week in the First 8 Weeks
Timepoint [3] 0 0
First 8 weeks
Secondary outcome [4] 0 0
Percent Change From Baseline in Mean Corrected Calcium During the Efficacy Assessment Phase
Timepoint [4] 0 0
Baseline and the efficacy assessment phase (weeks 20 - 27)
Secondary outcome [5] 0 0
Percentage of Participants With Mean Predialysis Serum Phosphorus = 4.5 mg/dL During the Efficacy Assessment Phase
Timepoint [5] 0 0
Efficacy assessment phase (weeks 20 - 27)
Secondary outcome [6] 0 0
Mean Severity of Nausea in the First 8 Weeks
Timepoint [6] 0 0
First 8 weeks
Secondary outcome [7] 0 0
Mean Number of Episodes of Vomiting Per Week in the First 8 Weeks
Timepoint [7] 0 0
First 8 weeks

Eligibility
Key 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
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Eligible subjects cannot have received cinacalcet during the 3 months preceding the
first screening laboratory assessment

- Other criteria may apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/08/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/01/2015
Sample size
Target
Accrual to date
Final
683
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Louisiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Mississippi
Country [8] 0 0
United States of America
State/province [8] 0 0
New Jersey
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Vermont
Country [15] 0 0
United States of America
State/province [15] 0 0
Virginia
Country [16] 0 0
United States of America
State/province [16] 0 0
Wisconsin
Country [17] 0 0
Austria
State/province [17] 0 0
Feldkirch
Country [18] 0 0
Austria
State/province [18] 0 0
Linz
Country [19] 0 0
Austria
State/province [19] 0 0
Wien
Country [20] 0 0
Belgium
State/province [20] 0 0
Genk
Country [21] 0 0
Belgium
State/province [21] 0 0
Hasselt
Country [22] 0 0
Belgium
State/province [22] 0 0
Kortrijk
Country [23] 0 0
Belgium
State/province [23] 0 0
Roeselare
Country [24] 0 0
Canada
State/province [24] 0 0
Alberta
Country [25] 0 0
Canada
State/province [25] 0 0
New Brunswick
Country [26] 0 0
Canada
State/province [26] 0 0
Newfoundland and Labrador
Country [27] 0 0
Canada
State/province [27] 0 0
Ontario
Country [28] 0 0
Canada
State/province [28] 0 0
Quebec
Country [29] 0 0
Czechia
State/province [29] 0 0
Novy Jicin
Country [30] 0 0
Czechia
State/province [30] 0 0
Praha 4 - Nusle
Country [31] 0 0
Czechia
State/province [31] 0 0
Praha 6
Country [32] 0 0
Czechia
State/province [32] 0 0
Slavkov u Brna
Country [33] 0 0
Czechia
State/province [33] 0 0
Trinec
Country [34] 0 0
Czechia
State/province [34] 0 0
Usti nad Orlici
Country [35] 0 0
Denmark
State/province [35] 0 0
Aalborg
Country [36] 0 0
Denmark
State/province [36] 0 0
Fredericia
Country [37] 0 0
Denmark
State/province [37] 0 0
Kobenhavn
Country [38] 0 0
Denmark
State/province [38] 0 0
Odense
Country [39] 0 0
Denmark
State/province [39] 0 0
Roskilde
Country [40] 0 0
Estonia
State/province [40] 0 0
Tallinn
Country [41] 0 0
Estonia
State/province [41] 0 0
Tartu
Country [42] 0 0
France
State/province [42] 0 0
Boulogne sur Mer
Country [43] 0 0
France
State/province [43] 0 0
Lille Cedex
Country [44] 0 0
France
State/province [44] 0 0
Nouilly
Country [45] 0 0
France
State/province [45] 0 0
Paris
Country [46] 0 0
France
State/province [46] 0 0
Saint Ouen
Country [47] 0 0
France
State/province [47] 0 0
Saint Priest en Jarez
Country [48] 0 0
France
State/province [48] 0 0
Saint-Ouen
Country [49] 0 0
France
State/province [49] 0 0
Sainte Foy les Lyon
Country [50] 0 0
Germany
State/province [50] 0 0
Aachen
Country [51] 0 0
Germany
State/province [51] 0 0
Coburg
Country [52] 0 0
Germany
State/province [52] 0 0
Hamburg
Country [53] 0 0
Germany
State/province [53] 0 0
Hannover
Country [54] 0 0
Germany
State/province [54] 0 0
Magdeburg
Country [55] 0 0
Germany
State/province [55] 0 0
Mettmann
Country [56] 0 0
Germany
State/province [56] 0 0
Minden
Country [57] 0 0
Germany
State/province [57] 0 0
München
Country [58] 0 0
Germany
State/province [58] 0 0
Wiesbaden
Country [59] 0 0
Germany
State/province [59] 0 0
Zwickau
Country [60] 0 0
Greece
State/province [60] 0 0
Alexandroupoli
Country [61] 0 0
Greece
State/province [61] 0 0
Athens
Country [62] 0 0
Greece
State/province [62] 0 0
Ioannina
Country [63] 0 0
Greece
State/province [63] 0 0
Larissa
Country [64] 0 0
Greece
State/province [64] 0 0
Nikaia, Piraeus
Country [65] 0 0
Greece
State/province [65] 0 0
Patra
Country [66] 0 0
Greece
State/province [66] 0 0
Thessaloniki
Country [67] 0 0
Hungary
State/province [67] 0 0
Budapest
Country [68] 0 0
Hungary
State/province [68] 0 0
Gyor
Country [69] 0 0
Hungary
State/province [69] 0 0
Kaposvar
Country [70] 0 0
Hungary
State/province [70] 0 0
Kistarcsa
Country [71] 0 0
Hungary
State/province [71] 0 0
Pecs
Country [72] 0 0
Hungary
State/province [72] 0 0
Szekesfehervar
Country [73] 0 0
Hungary
State/province [73] 0 0
Szigetvar
Country [74] 0 0
Hungary
State/province [74] 0 0
Zalaegerszeg
Country [75] 0 0
Italy
State/province [75] 0 0
Cagliari
Country [76] 0 0
Italy
State/province [76] 0 0
Firenze
Country [77] 0 0
Italy
State/province [77] 0 0
Genova
Country [78] 0 0
Italy
State/province [78] 0 0
Lecco
Country [79] 0 0
Italy
State/province [79] 0 0
Lucca
Country [80] 0 0
Italy
State/province [80] 0 0
Milano
Country [81] 0 0
Italy
State/province [81] 0 0
Pavia
Country [82] 0 0
Italy
State/province [82] 0 0
Pisa
Country [83] 0 0
Italy
State/province [83] 0 0
Pordenone
Country [84] 0 0
Italy
State/province [84] 0 0
San Giovanni Rotondo FG
Country [85] 0 0
Latvia
State/province [85] 0 0
Riga
Country [86] 0 0
Latvia
State/province [86] 0 0
Valmiera
Country [87] 0 0
Lithuania
State/province [87] 0 0
Alytus
Country [88] 0 0
Lithuania
State/province [88] 0 0
Kaunas
Country [89] 0 0
Lithuania
State/province [89] 0 0
Kedainiai
Country [90] 0 0
Lithuania
State/province [90] 0 0
Klaipeda
Country [91] 0 0
Lithuania
State/province [91] 0 0
Siauliai
Country [92] 0 0
Lithuania
State/province [92] 0 0
Ukmerge
Country [93] 0 0
New Zealand
State/province [93] 0 0
Hamilton
Country [94] 0 0
New Zealand
State/province [94] 0 0
Papatoetoe, Auckland
Country [95] 0 0
New Zealand
State/province [95] 0 0
Takapuna, Auckland City
Country [96] 0 0
Poland
State/province [96] 0 0
Gdansk
Country [97] 0 0
Poland
State/province [97] 0 0
Katowice
Country [98] 0 0
Poland
State/province [98] 0 0
Poznan
Country [99] 0 0
Poland
State/province [99] 0 0
Sieradz
Country [100] 0 0
Poland
State/province [100] 0 0
Wadowice
Country [101] 0 0
Poland
State/province [101] 0 0
Warsawa
Country [102] 0 0
Poland
State/province [102] 0 0
Warszawa
Country [103] 0 0
Poland
State/province [103] 0 0
Zabrze
Country [104] 0 0
Poland
State/province [104] 0 0
Zyrardow
Country [105] 0 0
Portugal
State/province [105] 0 0
Almada
Country [106] 0 0
Portugal
State/province [106] 0 0
Aveiro
Country [107] 0 0
Portugal
State/province [107] 0 0
Estoril
Country [108] 0 0
Portugal
State/province [108] 0 0
Forte Da Casa
Country [109] 0 0
Portugal
State/province [109] 0 0
Guimarães
Country [110] 0 0
Portugal
State/province [110] 0 0
Lisboa
Country [111] 0 0
Portugal
State/province [111] 0 0
Santo Tirso
Country [112] 0 0
Portugal
State/province [112] 0 0
Setubal
Country [113] 0 0
Portugal
State/province [113] 0 0
Vila Franca de Xira
Country [114] 0 0
Russian Federation
State/province [114] 0 0
Mitishi
Country [115] 0 0
Russian Federation
State/province [115] 0 0
Moscow
Country [116] 0 0
Russian Federation
State/province [116] 0 0
Petrozavodsk
Country [117] 0 0
Russian Federation
State/province [117] 0 0
Saint Petersburg
Country [118] 0 0
Russian Federation
State/province [118] 0 0
Saint-Petersburg
Country [119] 0 0
Russian Federation
State/province [119] 0 0
Yaroslavl
Country [120] 0 0
Spain
State/province [120] 0 0
Andalucía
Country [121] 0 0
Spain
State/province [121] 0 0
Cataluña
Country [122] 0 0
Spain
State/province [122] 0 0
Comunidad Valenciana
Country [123] 0 0
Spain
State/province [123] 0 0
Extremadura
Country [124] 0 0
Spain
State/province [124] 0 0
Navarra
Country [125] 0 0
Spain
State/province [125] 0 0
País Vasco
Country [126] 0 0
Spain
State/province [126] 0 0
Madrid
Country [127] 0 0
Sweden
State/province [127] 0 0
Malmö
Country [128] 0 0
Sweden
State/province [128] 0 0
Stockholm
Country [129] 0 0
Sweden
State/province [129] 0 0
Trollhättan
Country [130] 0 0
Switzerland
State/province [130] 0 0
Aarau
Country [131] 0 0
Switzerland
State/province [131] 0 0
Bern
Country [132] 0 0
Switzerland
State/province [132] 0 0
Geneva 14
Country [133] 0 0
Switzerland
State/province [133] 0 0
Lausanne
Country [134] 0 0
Switzerland
State/province [134] 0 0
Locarno
Country [135] 0 0
Switzerland
State/province [135] 0 0
Zurich
Country [136] 0 0
Turkey
State/province [136] 0 0
Ankara
Country [137] 0 0
Turkey
State/province [137] 0 0
Istanbul
Country [138] 0 0
Turkey
State/province [138] 0 0
Izmir

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01896232
Trial related presentations / publications
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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries