Safety, Tolerability and Efficacy of Etelcalcetide in Hemodialysis Patients With Secondary Hyperparathyroidism

A Double-Blind, Randomized, Placebo-Controlled Multiple Ascending Dose Study to Assess the Safety, Tolerability and Efficacy of KAI-4169 in Hemodialysis Subjects With Secondary Hyperparathyroidism

The purpose of this study is to characterize the safety and tolerability and efficacy of multiple ascending doses of etelcalcetide in hemodialysis patients for the treatment of secondary hyperparathyroidism (HPT).

Study Overview

• Status: Completed
• Conditions: Secondary Hyperparathyroidism
• Intervention / Treatment: Drug: Etelcalcetide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Azusa, California, United States, 91702
    • Costa Mesa, California, United States, 92626
    • Lynwood, California, United States, 90262
    • Riverside, California, United States, 92505
    • San Diego, California, United States, 92123
  • Colorado
    • Denver, Colorado, United States, 80218
  • Georgia
    • Macon, Georgia, United States, 31217
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
  • Minnesota
    • Brooklyn Center, Minnesota, United States, 55430
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19106
  • Texas
    • Houston, Texas, United States, 77004
    • Houston, Texas, United States, 77099
  • Virginia
    • Chesapeake, Virginia, United States, 23320

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject provides written informed consent.
• Intact parathyroid hormone (PTH) at least 350 pg/mL.
• Corrected calcium at least 9.0 mg/dL.
• Hemoglobin at least 9.0 g/dL.
• Adequate hemodialysis three times per week.
• Excepting chronic renal failure, subject is judged to be in stable medical condition based on medical history, physical examination, and routine laboratory tests.

Exclusion Criteria:

• History or symptomatic ventricular dysrhythmias.
• History of angina pectoris or congestive heart failure
• History of myocardial infarction, coronary angioplasty, or coronary artery bypass grafting within the past 6 months.
• History of or treatment for seizure disorder.
• Recent (3 months) parathyroidectomy.
• Serum transaminases (alanine aminotransferase, aspartate aminotransferase) greater than two times the upper limit of normal at screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Etelcalcetide; Participants received etelcalcetide administered by intravenous injection at the end of each hemodialysis session three times a week (TIW). The starting dose level was 5 mg; dose escalation was to proceed to 10 and 20 mg pending safety review of the prior cohort.	Drug: Etelcalcetide; Administered intravenously (IV) at the end of hemodialysis; Other Names: KAI-4169; AMG 416; Parsabiv™
Placebo Comparator: Placebo; Participants received placebo administered by intravenous injection at the end of each hemodialysis session three times a week (TIW).	Drug: Placebo; Administered intravenously at the end of hemodialysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Mean Pre-hemodialysis Parathyroid Hormone (PTH) During the Efficacy Assessment Phase	Baseline is defined as the average of pre-hemodialysis values obtained on day -2 and day 1. The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period.	Baseline and the efficacy assessment phase (EAP; defined as the period between 3 days before and 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With ≥ 30% Reduction From Baseline in Mean Parathyroid Hormone During the Efficacy Assessment Phase	Baseline is defined as the average of pre-hemodialysis values obtained on day -2 and day 1. The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period.	Baseline and the efficacy assessment phase (from 3 days before to 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3)
Percentage of Participants With Mean Parathyroid Hormone ≤ 300 pg/mL During the Efficacy Assessment Phase	The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period.	Efficacy assessment phase (from 3 days before to 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3)
Percent Change From Baseline in Mean Corrected Calcium (cCa) During the Efficacy Assessment Phase	Baseline is defined as the average of pre-hemodialysis values obtained on day -2 and day 1. The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period.	Baseline and the efficacy assessment phase (from 3 days before to 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3)
Percent Change From Baseline in Mean Phosphorus (P) During the Efficacy Assessment Phase	Baseline is defined as the average of pre-hemodialysis values obtained on day -2 and day 1. The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period.	Baseline and the efficacy assessment phase (from 3 days before to 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3)
Percent Change From Baseline in Corrected Calcium Phosphorus Product (cCa x P) During the Efficacy Assessment Phase	Baseline is defined as the average of pre-hemodialysis values obtained on day -2 and day 1. The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period.	Baseline and the efficacy assessment phase (from 3 days before to 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3)
Percentage of Participants With Mean Phosphorus ≤ 4.5 mg/dL or ≤ 5.5 mg/dL During the Efficacy Assessment Phase		Efficacy assessment phase

Collaborators and Investigators

• Sponsor: KAI Pharmaceuticals
• Investigators: Study Director: M D, Amgen

Study record dates

Study Major Dates

• Study Start: February 20, 2011
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): August 24, 2011

Study Registration Dates

• First Submitted: December 3, 2010
• First Submitted That Met QC Criteria: December 3, 2010
• First Posted (Estimate): December 6, 2010

Study Record Updates

• Last Update Posted (Actual): April 13, 2017
• Last Update Submitted That Met QC Criteria: March 1, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Renal Dialysis; Parathyroid hormone; Clinical Trial, Phase 2; Secondary Hyperparathyroidism
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Parathyroid Diseases; Neoplastic Processes; Hyperparathyroidism; Neoplasm Metastasis; Hyperparathyroidism, Secondary
• Other Study ID Numbers: KAI-4169-003; 20120330 (Other Identifier: Amgen, Inc)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No