Safety, Tolerability and Pharmacokinetics of Etelcalcetide in Healthy Male Volunteers

Phase 1

Completed

• Conditions: Hyperparathyroidism, Secondary
• Interventions: Drug: Placebo; Drug: Etelcalcetide

• Registration Number: NCT01134549
• Lead Sponsor: KAI Pharmaceuticals

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-05-28
• Study First Submitted QC: 2010-06-01
• Study First Posted: 2010-06-02
• Study Start: 2010-06-09
• Primary Completion: 2010-07-31
• Study Completion: 2010-07-31
• Status Verified: 2017-02
• Results First Submitted: 2017-02-28
• Results First Submitted QC: 2017-02-28
• Last Update Submitted: 2017-02-28
• Results First Posted: 2017-04-14
• Last Update Posted: 2017-04-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 32

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants received a single dose of placebo intravenous injection.
Etelcalcetide	Etelcalcetide	Participants received a single dose of etelcalcetide intravenous injection; the starting dose was 0.5 mg.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	From the first dose of study drug through 7 days.

Secondary Outcome Measures

Name	Time	Method
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
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
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 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 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 1,25 (OH)2 Vitamin D	Baseline and 12, 24, and 48 hours post-dose
Maximum Observed Concentration (Cmax) 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.	Plasma samples were analyzed for levels of etelcalcetide for pharmacokinetic (PK) analysis using a validated liquid chromatography/mass spectrometry (LC/MS) method.
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.
Number of Participants With Antibodies to Etelcalcetide	Samples for antibody analysis were collected pre-dose and between days 7-12 and days 21-28.	Serum samples were analyzed for antibodies against etelcalcetide using a validated enzyme-linked immunosorbent assay (ELISA).
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.