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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/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 - Participants completed the Nausea/Vomiting Symptom Assessment (NVSA) questionnaire daily. This questionnaire asked participants to indicate the severity of nausea on a scale from 0 (no nausea) to 10 (as severe as can be imagined) and if they had vomited in the past 24 hours. A day of vomiting or nausea was defined as those where the severity of nausea score was > 0 or where the episodes of vomiting score was > 0.
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 - Severity of nausea was assessed using the Nausea and Vomiting Symptom Assessment questionnaire which asked participants to rate the severity of nausea on a scale from 0 (no nausea) to 10 (as severe as can be imagined). For each participant, the mean severity of nausea was calculated by averaging all available daily severities (including zeroes) reported 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 - The number of vomiting episodes was assessed using the Nausea and Vomiting Symptom Assessment questionnaire which asks participants on a daily basis how many times they vomited in the past 24 hours. The number of episodes in a week is the sum of all reported daily episodes in the week.
For participants providing less than 7 days of responses to NVSA questions in any given week, data from that week did not contribute to the analysis.
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
Gender
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
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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/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. Review.
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.
Myles Wolf1, Geoffrey A. Block2, Glenn M. Chertow3, Kerry Cooper4, Bruno Fouqueray4, Sharon M. Moe5, Yan Sun4, Holly Tomlin4, Marc Vervloet 6 and Rainer Oberbauer7. Effects of etelcalcetide on fibroblast growth factor 23 in patients with secondary hyperparathyroidism receiving hemodialysis. Clin Kidney J. 2019;1-10.
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

Summary results
Other publications