A Phase 1 Study to Evaluate PK, Safety and Tolerability of AMG 416

Amgen

Status and phase: Completed; Phase 1

Conditions: Secondary Hyperparathyroidism

Treatments: Drug: Placebo; Drug: Etelcalcetide

Study type: Interventional

Funder types: Industry

Identifiers

NCT03283098

20140197

Details and patient eligibility

About

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.

Enrollment: 33 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

33 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Intravenous (IV) administration of placebo three times a week (TIW) for 4 weeks for a total of 12 doses. Participants were followed for an additional 4 weeks.

Treatment:

Drug: Placebo

Etelcalcetide

Experimental group

Description:

5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) for 4 weeks for a total of 12 doses. Participants were followed for an additional 4 weeks.

Treatment:

Drug: Etelcalcetide