Phase 1
Completed N=33
A Phase 1 Study to Evaluate PK, Safety and Tolerability of AMG 416
Source: ClinicalTrials.gov NCT03283098 ↗Enrolled (actual)
33
Serious AEs
9.1%
Results posted
Feb 2020
Primary outcomePrimary: Pharmacokinetic (PK) Parameter: Time to Maximum Drug Concentration (Tmax) of Plasma Etelcalcetide on Days 1 and 27 — 0.22; 0.22 hour
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Pharmacokinetic (PK) Parameter: Time to Maximum Drug Concentration (Tmax) of Plasma Etelcalcetide on Days 1 and 27 |
0.22; 0.22 | — |
| PRIMARY PK: Maximum Observed Drug Concentration (Cmax) of Plasma Etelcalcetide on Days 1 and 27 |
216; 236 | — |
| PRIMARY Pharmacokinetic (PK) Parameter: Area Under the Curve From Time Zero to the Beginning of the Subsequent Hemodialysis Treatment (AUClast) of Plasma Etelcalcetide on Days 1 and 27 |
1110; 3310 | — |
| PRIMARY Pharmacokinetic (PK) Parameter: Accumulation Ratio Comparing Days 1 and 27 |
3.02 | — |
| SECONDARY Participants With Treatment-Emergent Adverse Events (TEAEs) |
7; 25; 0; 5; 0; 1 | — |
| SECONDARY Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Participants With Clinically-Significant Changes in Electrocardiograms (ECGs) From Baseline to End of Study |
0; 2; 0; 1; 8; 21 | — |
| SECONDARY Change From Baseline to End of Study in Weight |
1.32; 0.76 | — |
| SECONDARY Change From Baseline to End of Study in Systolic and Diastolic Blood Pressures |
1.1; 6.1; 4.4; 1.5 | — |
| SECONDARY Baseline and Change From Baseline to End of Study in Heart Rate |
79.5; 82.8; -2.9; -1.4 | — |
| SECONDARY Change From Baseline to End of Study in Calcium |
-0.10; -0.07 | — |
| SECONDARY Change From Baseline to End of Study in Corrected Calcium (cCa) |
-0.08; -0.05 | — |
| SECONDARY Participants With Low Corrected Calcium (cCA) By Category |
0; 0; 0; 1; 0; 12 | — |
| SECONDARY Baseline and Change From Baseline to End of Study in Serum Albumin |
41.20; 39.37; -1.06; -0.59 | — |
| SECONDARY Change From Baseline to End of Study in Serum Phosphorus |
-0.03; -0.06 | — |
| SECONDARY Participants With Anti-etelcalcetide Antibody at Baseline and Postbaseline |
1; 0; 0 | — |
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 55 years with cessation of menses for 12 months or more
- Age 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
Data sourced from ClinicalTrials.gov (NCT03283098). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.