Head-to-Head Study of Etelcalcetide and Cinacalcet in Asian Hemodialysis Patients With Secondary Hyperparathyroidism (SHPT)
Condition: Secondary Hyperparathyroidism; Chronic Kidney Disease
MeSH terms: Neoplasm Metastasis; Kidney Diseases; Renal Insufficiency, Chronic; Hyperparathyroidism; Hyperparathyroidism, Secondary
Intervention: Etelcalcetide; Cinacalcet
Intervention description: Administered intravenously three times per week.; Cinacalcet administered orally once a day.
Intervention MeSH terms: Cinacalcet
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Participants will be randomized by Interactive Voice Response (IVR)/Interactive Web Response (IWR) in a 1:1 ratio to either three times per week (TIW) intravenous (IV) etelcalcetide (and daily oral placebo tablets) or daily oral cinacalcet tablets (and TIW IV placebo) in a double-blind, double-dummy manner. Treatment groups will be blinded to the investigator, participants, and the Amgen study team.
Enrollment: 637.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective is to demonstrate that treatment with etelcalcetide (AMG 416) is not
      inferior to treatment with cinacalcet for lowering serum intact parathyroid hormone (PTH)
      levels by > 30% from baseline among participants with chronic kidney disease (CKD) and
      secondary hyperparathyroidism (SHPT) who require management with hemodialysis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject has provided informed consent prior to performing any study-related
             activities/procedures.

          -  Male or female subjects ≥ 18 years of age or older at the time of signing informed
             consent.

          -  Subject must be receiving maintenance hemodialysis 3 times weekly for at least 3
             months, with adequate hemodialysis based on a delivered measure of dialysis adequacy
             (Kt/V) ≥ 1.2 or urea reduction ratio ≥ 65% within 4 weeks prior to screening
             laboratory assessments. The Kt/V formula used for a subject must be the formula used
             during routine care prior to screening.

          -  Dialysate calcium concentration must be ≥ 2.5 mEq/L (1.25 mmol/L) and stable for at
             least 4 weeks prior to screening laboratory assessments, and must remain ≥ 2.5 mEq/L
             (1.25 mmol/L) for the duration of the study.

          -  Subject must have SHPT as defined by one central laboratory screening predialysis
             serum PTH value > 500 pg/mL, within 2 weeks prior to randomization.

          -  Subject currently receiving vitamin D sterols must have had no more than a maximum
             dose change of 50% within the 4 weeks prior to screening laboratory assessments,
             remain stable through randomization, and be expected to maintain stable doses for the
             duration of the study, except for adjustments allowed per protocol or for safety
             reasons.

          -  Subject must have 1 screening predialysis serum cCa laboratory value ≥ 8.3 mg/dL
             measured within 2 weeks prior to randomization.

          -  A subject receiving calcium supplements must have had no more than a maximum dose
             change of 50% within 2 weeks prior to screening laboratory assessments and remain
             stable through randomization.

          -  A subject receiving phosphate binders must have had no more than a maximum dose change
             of 50% within the 2 weeks prior to screening laboratory assessments, remain stable
             through randomization, and be expected to maintain stable dose for the duration of the
             study, except for adjustments allowed per protocol or for safety reasons.

        Exclusion Criteria:

          -  Currently receiving treatment in another investigational device or drug study, or ≤ 30
             days since ending treatment on another investigational device or drug study(s). Other
             investigational procedures while participating in this study are excluded.

          -  Subject has received etelcalcetide in a prior clinical trial of etelcalcetide.

          -  Subject has received cinacalcet during the 3 months prior to the first screening
             laboratory assessments.

          -  Subject has known sensitivity to any of the products or components of either
             cinacalcet or etelcalcetide to be administered during dosing.

          -  Subject has previously been randomized in this study.

          -  Anticipated or scheduled parathyroidectomy during the study period.

          -  Subject has received a parathyroidectomy within 6 months prior to dosing.

          -  Anticipated or scheduled kidney transplant during the study period.

          -  Subject has an unstable medical condition based on medical history, physical
             examination, and routine laboratory tests, or is otherwise unstable in the judgment of
             the Investigator.

          -  Malignancy within the last 5 years of screening (except non-melanoma skin cancers or
             cervical carcinoma in situ).

          -  Grapefruit juice is prohibited.

          -  Subject is pregnant or nursing, or planning to become pregnant or nurse during
             treatment or within 3 months after the last dose of etelcalcetide or 30 days after the
             last dose of cinacalcet

          -  Female subject of childbearing potential who is unwilling to use an acceptable method
             of effective contraception during treatment with investigational product (IP) through
             3 months after the last dose of IP.

          -  Subject has a history of symptomatic ventricular dysrhythmias or Torsades de Pointes.

          -  Subject has a history of myocardial infarction, coronary angioplasty, or coronary
             arterial bypass grafting within the past 6 months prior to screening.

          -  Subject has clinically significant abnormalities on prestudy clinical examination or
             abnormalities on the most recent central laboratory tests during the screening period
             prior to randomization according to the Investigator including but not limited to the
             following:

               -  serum albumin < 3.0 g/dL

               -  serum magnesium < 1.5 mg/dL

               -  serum transaminase (alanine transaminase [ALT] or serum glutamic pyruvic
                  transaminase [SGPT], aspartate aminotransferase [AST] or serum glutamic
                  oxaloacetic transaminase [SGOT]) > 3 times the upper limit of normal (ULN) at
                  screening.

          -  Subject likely not available to complete all protocol-required study visits or
             procedures, and/or to comply with all required study procedures to the best of the
             subject and Investigator's knowledge.

          -  History or evidence of any other clinically significant disorder, condition or disease
             (with the exception of those outlined above) that, in the opinion of the Investigator
             or Amgen physician, if consulted, would pose a risk to subject safety or interfere
             with the study evaluation, procedures or completion.