Safety, Tolerability and Pharmacokinetics of Etelcalcetide in Healthy Male Volunteers

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

Official Title
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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

Conditions
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Hyperparathyroidism, Secondary

Intervention / Treatment
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* Drug: Etelcalcetide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received a single dose of placebo intravenous injection. | Drug: Placebo<br>* Administered as a single intravenous (IV) injection<br>|
| Experimental: Etelcalcetide<br>Participants received a single dose of etelcalcetide intravenous injection; the starting dose was 0.5 mg. | Drug: Etelcalcetide<br>* Administered as a single intravenous (IV) injection<br>* Other names: Parsabiv™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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. |