Neoplasms

Symptoms and General Pathology

All Conditions

Gland and Hormone Related Diseases

Neoplasm Metastasis

Hyperparathyroidism

Hyperparathyroidism, Secondary

Neoplastic Processes

Parathyroid Diseases

Endocrine System Diseases

All Drugs and Chemicals

Hormones

Parathyroid Hormone

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.

Participants received placebo administered by intravenous injection at the end of each hemodialysis session three times a week (TIW).

Administered intravenously (IV) at the end of hemodialysis

Etelcalcetide

Administered intravenously at the end of hemodialysis

Placebo

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).

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

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.

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.

KAI Pharmaceuticals

Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Participants received placebo administered by intravenous injection at the end of each hemodialysis session TIW for 2 weeks.

Cohort 1: Placebo

Participants received 5 mg etelcalcetide administered by intravenous injection at the end of each hemodialysis session TIW for 2 weeks.

Cohort 1: Etelcalcetide 5 mg

Participants received placebo administered by intravenous injection at the end of each hemodialysis session TIW for 4 weeks.

Cohort 2: Placebo

Participants received 10 mg etelcalcetide administered by intravenous injection at the end of each hemodialysis session TIW for 4 weeks.

Cohort 2: Etelcalcetide 10 mg

Cohort 3: Placebo

Participants received 5 mg etelcalcetide administered by intravenous injection at the end of each hemodialysis session TIW for 4 weeks.

Cohort 3: Etelcalcetide 5 mg

Participants received placebo administered by intravenous injection at the end of each hemodialysis session three times a week (TIW) for 2 weeks.

Total

Age, Continuous

Sex: Female, Male

Race

Ethnicity

Stratification Factor: Screening Serum Parathyroid Hormone (PTH)

Corrected calcium data were missing for 2 participants in Cohort 3.

Corrected Calcium

Phosphorus values were not collected at Baseline for Cohort 1; data were missing for 7 participants in Cohort 2 and 2 participants in Cohort 3.

Phosphorus

All randomized participants who received at least one 1 dose of investigational product (the modified intent-to-treat \[mITT\] population)

Study Director

The hypothesis for this study (Cohorts 2 and 3) was that intravenous administration of etelcalcetide is superior to placebo for the reduction of PTH after TIW dosing in hemodialysis patients with secondary HPT. This hypothesis was tested in Cohorts 2 and 3 by comparing the mean percent changes from baseline in pre-hemodialysis PTH levels collected during the efficacy phase between the etelcalcetide and placebo groups within each cohort.

Percent Change From Baseline in Mean Pre-hemodialysis Parathyroid Hormone (PTH) During the Efficacy Assessment Phase

Percentage of Participants With ≥ 30% Reduction From Baseline in Mean Parathyroid Hormone During the Efficacy Assessment Phase

Percentage of Participants With Mean Parathyroid Hormone ≤ 300 pg/mL During the Efficacy Assessment Phase

Modified intent-to-treat population with available data

Percent Change From Baseline in Mean Corrected Calcium (cCa) During the Efficacy Assessment Phase

Modified intent-to-treat population with available data; Phosphorus data were not collected at baseline for participants in Cohort 1.

Percent Change From Baseline in Mean Phosphorus (P) During the Efficacy Assessment Phase

Percent Change From Baseline in Corrected Calcium Phosphorus Product (cCa x P) During the Efficacy Assessment Phase

Phosphorus ≤ 4.5 mg/dL

Phosphorus ≤ 5.5 mg/dL

Percentage of Participants With Mean Phosphorus ≤ 4.5 mg/dL or ≤ 5.5 mg/dL During the Efficacy Assessment Phase

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Musculoskeletal Diseases

Nutritional and Metabolic Diseases

Rare Diseases

Kidney Diseases

Bone Diseases

Chronic Kidney Disease-Mineral and Bone Disorder

Rickets

Bone Diseases, Metabolic

Urologic Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Metabolic Diseases

Calcium Metabolism Disorders

Vitamin D Deficiency

Avitaminosis

Deficiency Diseases

Malnutrition

Nutrition Disorders

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Central Nervous System Depressants

Other Dietary Supplements

Benzocaine

Tannic Acid

Participants received a bolus IV injection of etelcalcetide 3 times a week (TIW) at the end of each hemodialysis session for up to 144 weeks in the extension study. The starting dose was the same as the final dose administered in the parent study (20120331); the dose was adjusted per protocol-specified guidelines to achieve or maintain parathyroid hormone values in the 150 to 300 pg/mL range.

Administered as an intravenous bolus three times a week at the end of each hemodialysis session at dosages up to a maximum of 15 mg.

The purpose of this study is to evaluate the long term safety and efficacy of thrice weekly intravenous (IV) administration of etelcalcetide in the treatment of secondary hyperparathyroidism (SHPT) in patients receiving hemodialysis who had completed 12 weeks of treatment with etelcalcetide in parent study 20120331 (KAI-4169-005; NCT01414114).

Open-label Study to Assess the Long-term Safety and Efficacy of Etelcalcetide (Also Known as AMG 416 or KAI-4169) in Patients With Secondary Hyperparathyroidism

A Multicenter Open-label Extension Study to Assess the Long-term Safety and Efficacy of KAI-4169 (Also Known as AMG 416) in the Treatment of Chronic Kidney Disease-Mineral and Bone Disorder in Patients With Secondary Hyperparathyroidism

Baseline was defined as the average of 3 predialysis results obtained within 3 weeks before the first dose of etelcalcetide in the parent study (20120331).

The week numbering for this study continued from the parent study 20120331 hence the first measurement for all parameters in the extension study started at week 13.

Baseline was defined as the average of 3 predialysis results obtained within 3 weeks before the first dose of study drug in the parent study (20120331).

The week numbering for this study continued from the parent study 20120331; the first measurement for all parameters in the extension study started at week 13.

Participants received a bolus IV injection of etelcalcetide 3 times a week at the end of each hemodialysis session for up to 144 weeks in the extension study. The starting dose was the same as the final dose administered in the parent study (20120331); the dose was adjusted per protocol-specified guidelines to achieve or maintain parathyroid hormone values in the 150 to 300 pg/mL range.

Participants received a bolus intravenous (IV) injection of etelcalcetide 3 times a week (TIW) at the end of each hemodialysis session for up to 144 weeks in the extension study. The starting dose was the same as the final dose administered in the parent study (20120331); the dose was adjusted per protocol-specified guidelines to achieve or maintain parathyroid hormone values in the 150 to 300 pg/mL range.

Serum Corrected Calcium

Serum Phosphorus

Baseline was defined as the baseline of the parent study, 20120331.

Any adverse event (AE)

Serious adverse events

Treatment-related adverse events

Treatment-related serious adverse events

AEs leading to discontinuation of treatment

Fatal adverse events

Participants who received at least one dose of etelcalcetide in the extension study

Number of Participants With Adverse Events

Week 13

Week 26

Week 52

The full analysis set (all participants who received at least 1 dose during the extension study) with data collected on or before the last non-missing dose of etelcalcetide (defined as on-treatment approach).

Percent Change From Baseline in Parathyroid Hormone

Percent Change From Baseline in Serum Corrected Calcium

Percent Change From Baseline in Serum Phosphorus

Extension Period 1

Extension Period 2

Participants received a single dose of placebo intravenous (IV) injection after hemodialysis.

Participants received a single dose of etelcalcetide by intravenous (IV) injection after hemodialysis.

Single IV injection. The initial dose was 5 mg and dose escalation proceeded with subsequent doses of 10 mg, 20 mg, 40 mg and 60 mg.

Gregory Bell, MD

The purpose of this study is to characterize the safety and tolerability of single rising doses of etelcalcetide in hemodialysis patients with secondary hyperparathyroidism.

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

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

Pooled Placebo

Participants received a single dose of 5 mg etelcalcetide IV injection after hemodialysis.

Etelcalcetide 5 mg

Participants received a single dose of 10 mg etelcalcetide IV injection after hemodialysis.

Etelcalcetide 10 mg

Participants received a single dose of 20 mg etelcalcetide IV injection after hemodialysis.

Etelcalcetide 20 mg

Participants received a single dose of 40 mg etelcalcetide IV injection after hemodialysis.

Etelcalcetide 40 mg

Participants received a single dose of 60 mg etelcalcetide IV injection after hemodialysis.

Etelcalcetide 60 mg

Participants in Cohort 1 received single doses of 5 mg etelcalcetide and placebo in a crossover design, 7-14 days apart

Cohort 1: Placebo/Etelcalcetide 5 mg

Participants in Cohort 2 received single doses of 10 mg etelcalcetide and placebo in a crossover design, 7-14 days apart

Cohort 2: Placebo/Etelcalcetide 10 mg

Participants in Cohort 3 received single doses of 20 mg etelcalcetide and placebo in a crossover design, 7-14 days apart

Cohort 3: Placebo/Etelcalcetide 20 mg

Participants in Cohort 4 received a single dose of 40 mg etelcalcetide or placebo in a parallel group design.

Cohort 4: Placebo/Etelcalcetide 40 mg

Participants in Cohort 5 received a single dose of 60 mg etelcalcetide or placebo in a parallel group design.

Cohort 5: Placebo/Etelcalcetide 60 mg

Any adverse events

Withdrawal due to adverse events

Deaths due to adverse events

All participants who were randomized and received any amount of study medication.

30 Minutes

1 Hour

4 Hours

8 Hours

18 Hours

24 Hours

32 Hours

42 Hours

48 Hours

56 Hours

Day 4-Discharge

Day 8

Day 15

Day 29

Participants received a single dose of placebo IV injection after hemodialysis.

Participants who were randomized and received any amount of study medication with available data at each time point. Only participants in Cohorts 4 and 5 had PTH assessed on days 8, 15 and 29.

Percent Change From Baseline in Serum Parathyroid Hormone (PTH)

Participants who were randomized and received any amount of study medication and with available data at each time point. Only participants in Cohorts 4 and 5 had serum corrected calcium assessed on days 8, 15 and 29.

Participants who were randomized and received any amount of study medication with available data at each time point

Percent Change From Baseline in Ionized Calcium

Participants who were randomized and received any amount of study medication with available data at each time point.

Percent Change From Baseline in Calcium Phosphorus Product

Participants who were randomized and received any amount of etelcalcetide.

Maximum Observed Plasma Concentration (Cmax) of Etelcalcetide

Participants who were randomized and received any amount of etelcalcetide with available data.

Area Under the Concentration-time Curve From Time 0 to 65 Hours Post-dose for Etelcalcetide

Participants who were randomized and received any amount of etelcalcetide and with available data; The half-life associated with the terminal (log-linear) elimination phase values for the 40 mg dose level were not calculated due to poor log linear regression of the log concentration versus time profile during the terminal phase (r2 values \<0.7).

Observed Area Under the Concentration-time Curve Extrapolated to Infinity (AUCINFobs) for Etelcalcetide

Participants who were randomized and received any amount of etelcalcetide and with available data.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety, Tolerability and Efficacy of Etelcalcetide in Hemodialysis Patients With Secondary Hyperparathyroidism	NCT01254565	Secondary Hyper...	Etelcalcetide Placebo	18 Years -	KAI Pharmaceuticals
Open-label Study to Assess the Long-term Safety and Efficacy of Etelcalcetide (Also Known as AMG 416 or KAI-4169) in Patients With Secondary Hyperparathyroidism	NCT01576146	Secondary Hyper...	Etelcalcetide	18 Years -	KAI Pharmaceuticals
Safety, Tolerability and Pharmacokinetics of Etelcalcetide in Hemodialysis Patients With Secondary Hyperparathyroidism	NCT01134562	Hyperparathyroi...	Placebo Etelcalcetide	18 Years -	KAI Pharmaceuticals
Open-label Study to Assess the Long-term Safety and Efficacy of Etelcalcetide (Also Known as AMG 416 or KAI-4169) in Patients With Secondary Hyperparathyroidism	NCT01576146	Secondary Hyper...	Etelcalcetide	18 Years -	KAI Pharmaceuticals
Safety, Tolerability and Pharmacokinetics of Etelcalcetide in Hemodialysis Patients With Secondary Hyperparathyroidism	NCT01134562	Hyperparathyroi...	Placebo Etelcalcetide	18 Years -	KAI Pharmaceuticals

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