A Phase 1 Study to Evaluate PK, Safety and Tolerability of AMG 416
Condition: Secondary Hyperparathyroidism
MeSH terms: Hyperparathyroidism; Hyperparathyroidism, Secondary
Intervention: Etelcalcetide; Placebo
Intervention description: Etelcalcetide was supplied as a sterile, preservative-free, aqueous solution in a single-use 3 mL glass vial.; Placebo supplied to match active intervention.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a multiple dose, double-blind, randomized, placebo-controlled clinical study conducted in Chinese subjects residing in Mainland China with chronic kidney disease receiving hemodialysis. The treatment duration will be approximately 4 weeks with a post treatment followup of 4 weeks. A dose will be given at each scheduled hemodialysis session (Dose administered three times a week for 4 weeks, for a total of 12 doses).
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Secondary hyperparathyroidism; Chronic kidney disease CKD; Intact parathyroid hormone iPTH; Hemodialysis

Summary:

      This was a multiple-dose, double-blind, randomized, placebo-controlled study. Chinese
      subjects residing in Mainland China with chronic kidney disease (CKD) receiving hemodialysis
      were randomized in a 3:1 ratio to receive 5 mg intravenous (IV) of etelcalcetide or placebo 3
      times a week (TIW) for approximately 4 weeks, with a subsequent follow up period of
      approximately 4 weeks.

      Doses were given at the end of each scheduled hemodialysis session on study days 1 through
      day 27 and subject participation was complete after day 55 end-of-study (EOS) procedures were
      performed. Doses were administered TIW for 4 weeks, for a total of 12 doses.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject has provided informed consent prior to initiation of any study-specific
             activities/procedures

          -  Resident in Mainland China and of Chinese ancestry

          -  Male or female subject ≥ 18 and ≤ 70 years of age at the time of screening, with end
             stage renal disease receiving hemodialysis

          -  Subject must be receiving hemodialysis 3 times weekly for at least 3 months through a
             functioning permanent dialysis access prior to Day -2 and have adequate hemodialysis
             with a delivered Kt/V ≥ 1.2 or urea reduction ratio (URR) ≥ 65% within 4 weeks to
             screening. The subject's routine hemodialysis session must be of 3-4.5 hours in
             duration, inclusive

          -  Subject has stable dialysis prescription and this prescription is not anticipated to
             significantly change during the course of the study

        Exclusion Criteria:

          -  Corrected calcium (calculated) level is < 2.07 mmol/L (8.3 mg/dL), and/or intact PTH
             level is outside the range of 31.8 - 127.3 pmol/L (300 - 1200 pg/mL)

          -  Female subjects who are pregnant, lactating/breastfeeding, or who plan to conceive, or
             breastfeed while on study through 3 months after receiving the dose of study drug

          -  Female subject of reproductive potential not willing to use a(n) acceptable method(s)
             of effective birth control during treatment with AMG 416, and for an additional 3
             months after the end of treatment with AMG 416. Female subjects who have had a
             hysterectomy, bilateral salpingectomy, bilateral oophorectomy, bilateral tubal
             ligation, or who are postmenopausal are not required to use contraception.
             Postmenopausal is defined as:

               -  Age > 55 years with cessation of menses for 12 months or more

               -  Age < 55 but no spontaneous menses for at least 2 years

               -  Age < 55 years and spontaneous menses within the past 1 years, but currently
                  amenorrheic, AND with postmenopausal gonadrotropin levels (luteinizing hormone
                  and follicle-stimulating hormone levels > 40 IU/L) or postmenopausal estradiol
                  levels (<5.3 pmol/L or 5 ng/dL) or according to the definition of "postmenopausal
                  range" for the laboratory involved

               -  Underwent a bilateral oophorectomy

          -  Females of reproductive potential with a positive pregnancy test, unless medical
             follow-up confirms the subject is not pregnant

          -  Previous administration of AMG 416

          -  Subject has received cinacalcet within the 30 days prior to informed consent
             (treatment with cinacalcet is prohibited during the study)

          -  Subject has lost 500 mL or more of blood or plasma within 8 weeks of study drug
             administration or during the study period

          -  Anticipated or scheduled to have major surgical procedures during the study period
             such as kidney transplant or parathyroidectomy

          -  History of malignancy within 5 years before Day -2 (except non melanoma skin cancers,
             or cervical carcinoma in situ)

          -  Subject's 12-lead electrocardiogram (ECG) at screening suggests unstable arrhythmia or
             other cardiac abnormality that could place the subject at increased risk, based upon
             the Investigator's opinion

          -  Subject has current or history of cardiovascular conditions such as uncontrolled
             hypertension, symptomatic ventricular dysrhythmias, Torsades de Pointes, angina
             pectoris congestive heart failure (New York Heart Association Classification III or
             IV), myocardial infarction, coronary angioplasty, or coronary arterial bypass grafting
             within the past 6 months prior to screening