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

• ClinicalTrials.gov Identifier: NCT01254565
• Recruitment Status: Completed
• First Posted: December 6, 2010
• Results First Posted: April 13, 2017
• Last Update Posted: April 13, 2017
• Sponsor: KAI Pharmaceuticals
• Information provided by (Responsible Party): KAI Pharmaceuticals

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Secondary Hyperparathyroidism	Drug: Etelcalcetide; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 87 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: February 20, 2011
• Actual Primary Completion Date: July 2011
• Actual Study Completion Date: August 24, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Percent Change From Baseline in Mean Pre-hemodialysis Parathyroid Hormone (PTH) During the Efficacy Assessment Phase [ Time Frame: 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) ]
   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.

Secondary Outcome Measures :

1. Percentage of Participants With ≥ 30% Reduction From Baseline in Mean Parathyroid Hormone During the Efficacy Assessment Phase [ Time Frame: 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) ]
   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.
2. Percentage of Participants With Mean Parathyroid Hormone ≤ 300 pg/mL During the Efficacy Assessment Phase [ Time Frame: 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) ]
   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.
3. Percent Change From Baseline in Mean Corrected Calcium (cCa) During the Efficacy Assessment Phase [ Time Frame: 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) ]
   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.
4. Percent Change From Baseline in Mean Phosphorus (P) During the Efficacy Assessment Phase [ Time Frame: 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) ]
   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.
5. Percent Change From Baseline in Corrected Calcium Phosphorus Product (cCa x P) During the Efficacy Assessment Phase [ Time Frame: 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) ]
   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.
6. Percentage of Participants With Mean Phosphorus ≤ 4.5 mg/dL or ≤ 5.5 mg/dL During the Efficacy Assessment Phase [ Time Frame: Efficacy assessment phase ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

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

United States, Colorado

Denver, Colorado, United States, 80218

United States, Georgia

Macon, Georgia, United States, 31217

United States, Louisiana

Shreveport, Louisiana, United States, 71101

United States, Minnesota

Brooklyn Center, Minnesota, United States, 55430

United States, Pennsylvania

Philadelphia, Pennsylvania, United States, 19106

United States, Texas

Houston, Texas, United States, 77004

Houston, Texas, United States, 77099

United States, Virginia

Chesapeake, Virginia, United States, 23320

Sponsors and Collaborators

KAI Pharmaceuticals

Investigators

• Study Director: M D; Amgen

More Information

• Responsible Party: KAI Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01254565
• Other Study ID Numbers: KAI-4169-003; 20120330 ( Other Identifier: Amgen, Inc )
• First Posted: December 6, 2010
• Results First Posted: April 13, 2017
• Last Update Posted: April 13, 2017
• Last Verified: March 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by KAI Pharmaceuticals:

Clinical Trial, Phase 2; Renal Dialysis; Secondary Hyperparathyroidism; Parathyroid hormone

Additional relevant MeSH terms:

Neoplasm Metastasis; Hyperparathyroidism; Hyperparathyroidism, Secondary; Neoplastic Processes; Neoplasms; Pathologic Processes; Parathyroid Diseases; Endocrine System Diseases