Safety, Tolerability and Pharmacokinetics of Etelcalcetide in Healthy Male Volunteers

A Double-Blind, Randomized, Placebo-Controlled, Rising Single Intravenous Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of KAI-4169 in Healthy Male Volunteers

The purpose of this study is to characterize the safety and tolerability of etelcalcetide in healthy young males.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male between 18 and 45 years of age who have provided written informed consent
• Subject is judged to be in good health based on medical history, physical examination, and routine laboratory tests

Exclusion Criteria:

• History or presence of any significant acute or chronic illness (e.g., cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, or neurologic disease) according to the investigator
• History of any ongoing medical condition requiring treatment with prescription medication
• History of asthma, severe allergies including skin reactions or prior anaphylactic type reactions
• Clinically significant abnormalities on screening clinical examination or laboratory safety tests
• History of drug or alcohol abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received a single dose of placebo intravenous injection.	Drug: Placebo; Administered as a single intravenous (IV) injection
Experimental: Etelcalcetide; Participants received a single dose of etelcalcetide intravenous injection; the starting dose was 0.5 mg.	Drug: Etelcalcetide; Administered as a single intravenous (IV) injection; Other Names: KAI-4169; AMG 416; Parsabiv™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Adverse Events	From the first dose of study drug through 7 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Serum Parathyroid Hormone		Baseline and 10 minutes, 30 minutes, 1 hour, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 36, 42 and 48 hours post-dose
Percent Change From Baseline in Plasma Ionized Calcium		Baseline and 10 minutes, 30 minutes, 1 hour, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 36, 42 and 48 hours post-dose
Change From Baseline in Serum Total Calcium		Baseline and 10 minutes, 30 minutes, 1 hour, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 36, 42 and 48 hours post-dose
Change From Baseline in Serum Corrected Calcium		Baseline and 10 minutes, 30 minutes, 1 hour, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 36, 42 and 48 hours post-dose
Change From Baseline in Serum Phosphate		Baseline and 10 minutes, 30 minutes, 1 hour, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 36, 42 and 48 hours post-dose
Percent Change From Baseline in Serum Calcitonin		Baseline and 10 minutes, 30 minutes, 3, 12, 24, and 48 hours post-dose
Percent Change From Baseline in Serum 1,25 (OH)2 Vitamin D		Baseline and 12, 24, and 48 hours post-dose
Maximum Observed Concentration (Cmax) for Etelcalcetide	Plasma samples were analyzed for levels of etelcalcetide for pharmacokinetic (PK) analysis using a validated liquid chromatography/mass spectrometry (LC/MS) method.	Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.
Area Under the Concentration-time Curve Between the Time of Dose and the Last Time Point (AUCall) for Etelcalcetide		Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.
Observed Area Under the Concentration-time Curve Extrapolated to Infinity (AUCINFobs) for Etelcalcetide		Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.
Percent Observed Area Under the Concentration-time Curve Extrapolated to Infinity Resulting From Extrapolation to Concentration of 0 ng/mL (AUC%Extrapobs)		Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.
Terminal Elimination Rate Constant (λz) for Etelcalcetide		Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.
Half-life Associated With the Terminal (Log-linear) Elimination Phase (HLλz) for Etelcalcetide		Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.
Total Body Clearance (CL) for Etelcalcetide		Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.
Volume of Distribution at Steady State for Etelcalcetide		Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.
Number of Participants With Antibodies to Etelcalcetide	Serum samples were analyzed for antibodies against etelcalcetide using a validated enzyme-linked immunosorbent assay (ELISA).	Samples for antibody analysis were collected pre-dose and between days 7-12 and days 21-28.

Collaborators and Investigators

• Sponsor: KAI Pharmaceuticals
• Collaborators: Nucleus Network Ltd
• Investigators: Study Director: M D, Amgen

Study record dates

Study Major Dates

• Study Start: June 9, 2010
• Primary Completion (Actual): July 31, 2010
• Study Completion (Actual): July 31, 2010

Study Registration Dates

• First Submitted: May 28, 2010
• First Submitted That Met QC Criteria: June 1, 2010
• First Posted (Estimate): June 2, 2010

Study Record Updates

• Last Update Posted (Actual): April 14, 2017
• Last Update Submitted That Met QC Criteria: February 28, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Parathyroid Diseases; Hyperparathyroidism; Hyperparathyroidism, Secondary
• Other Study ID Numbers: KAI-4169-001; 20130107 (Other Identifier: Amgen, Inc)