Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Neoplasms

Symptoms and General Pathology

Gland and Hormone Related Diseases

Nutritional and Metabolic Diseases

Rare Diseases

Kidney Diseases

Neoplasm Metastasis

Hyperparathyroidism

Hyperparathyroidism, Secondary

Hypocalcemia

Renal Insufficiency, Chronic

Renal Insufficiency

Urologic Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Chronic Disease

Disease Attributes

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Parathyroid Diseases

Endocrine System Diseases

Chronic Graft Versus Host Disease

All Drugs and Chemicals

Bone Density Conservation Agents

Hormones

Calcium

Calcium, Dietary

Parathyroid Hormone

Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session three times a week, for 26 weeks.

Participants received placebo administered by intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks.

Administered intravenously three times per week. The starting dose was 5 mg. The dose may have been increased at 4-week intervals by 2.5 mg or 5 mg on the basis of the predialysis parathyroid hormone and corrected calcium concentrations obtained in the prior week. The minimum dose was 2.5 mg and the maximum dose was 15 mg.

Etelcalcetide

Administered intravenously (IV) three times per week.

Placebo

This study is designed to assess the efficacy and safety of etelcalcetide compared with placebo in the treatment of SHPT in patients with chronic kidney disease (CKD) receiving hemodialysis.

Efficacy and Safety of Etelcalcetide (AMG 416) in the Treatment of Secondary Hyperparathyroidism (SHPT) in Patients With Chronic Kidney Disease on Hemodialysis

A Randomized, Double-blind, Placebo-controlled, Phase 3 Study to Assess the Efficacy and Safety of AMG 416 in the Treatment of Secondary Hyperparathyroidism in Subjects With Chronic Kidney Disease on Hemodialysis

Participants who did not have any scheduled assessments during the EAP were considered non-responders.

Participants who had no scheduled assessments during the EAP were considered non-responders.

Amgen

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

Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session, TIW, for 26 weeks. The starting dose was 5 mg and may have been increased at weeks 5, 9, 13 and 17 to achieve a predialysis PTH ≤ 300 pg/mL.

Total

Age, Continuous

Sex: Female, Male

American Indian or Alaska Native

Asian

Black (or African American)

Native Hawaiian or Other Pacific Islander

White

Other

Missing

Race

< 600 pg/mL

≥ 600 to ≤ 1000 pg/mL

> 1000 pg/mL

Mean screening parathyroid hormone (PTH) obtained within 2 weeks prior to randomization.

Stratification Factor: Mean Screening Serum Parathyroid Hormone (PTH)

Stratification Factor: Cinacalcet Use Within 8 Weeks of Randomization

North America

Non-North America

Stratification Factor: Region

Parathyroid Hormone (PTH)

Data were available for 250 subjects in each treatment group.

Phosphorus

Corrected Calcium

Data were available for 249 and 250 subjects in each treatment group respectively.

Corrected Calcium Phosphorus Product (cCa x P)

Study Director

A Cochran-Mantel-Haenszel test stratified by screening PTH category (\< 600, ≥ 600 to ≤ 1000, and \> 1000 pg/mL), recent cinacalcet use within 8 weeks before randomization (yes and no), and region (North America and non-North America) was used to compare the primary endpoint of proportion of participants with \> 30% reduction from baseline in PTH during the EAP between etelcalcetide and placebo.

The full analysis set, consisting of all randomized participants

Percentage of Participants With a > 30% Decrease From Baseline in Mean PTH During the Efficacy Assessment Phase

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

Full analysis set participants with observed data

Percent Change From Baseline in Predialysis PTH During the Efficacy Assessment Phase

Percent Change From Baseline in Predialysis Corrected Calcium During the Efficacy Assessment Phase

Percent Change From Baseline in Predialysis Corrected Calcium Phosphorus Product During the Efficacy Assessment Phase

Percent Change From Baseline in Predialysis Phosphorus During the Efficacy Assessment Phase

Overall Study

Cinacalcet

Participants were treated with 5 mg etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session three times per week (TIW) for 4 weeks.

Etelcalcetide is provided as a sterile lyophilized powder to be reconstituted with sterile water for injection.

This is a multicenter, multiple-dose, single-arm, open-label study to assess the impact on serum corrected calcium levels when switching patients from cinacalcet to etelcalcetide (AMG 416).

Study to Assess the Impact on Calcium Levels When Hemodialysis Patients With Secondary Hyperparathyroidism (SHPT) Switch From Cinacalcet to Etelcalcetide

A Multicenter, Multiple-dose, Single-arm Study to Switch Hemodialysis Subjects With Secondary Hyperparathyroidism From Oral Cinacalcet HCl to Intravenous AMG 416

Hpocalcemia was used for events of decreased calcium accompanied by clinical signs and symptoms of hypocalcemia.

< 65 years

≥ 65 years

Age, Customized

Hispanic/Latino

Not Hispanic/Latino

Ethnicity

When albumin was less than 4.0 g/dL, the calcium level was corrected according to the following formula:

Corrected calcium (cCa) (mg/dL) = total Ca (mg/dL) + (4 - albumin \[g/dL\]) \* 0.8.

Full analysis set includes iall participants who enrolled into the study and had at least one dose of etelcalcetide and at least one post-baseline serum corrected calcium value.

Percentage of Participants With Serum Corrected Calcium < 7.5 mg/dL During the 4-week Treatment Period

Week 2 (n = 125)

Week 3 (n = 131)

Week 4 (n = 123)

Full analysis set with available data at each time point

Percent Change From Baseline in Parathyroid Hormone During the Treatment Period

Percentage of Participants With Serum Corrected Calcium < 8.3 mg/dL During the 4-week Treatment Period

Any adverse event (AE)

Serious adverse event (SAE)

AE leading to discontinuation of etelcalcetide

Fatal adverse event

Treatment-related adverse event

All participants who received at least one dose of study drug

Number of Participants With Adverse Events

Participants who received at least one dose of study drug

Percentage of Participants With Symptomatic Hypocalcemia During the 4-week Treatment Period

Participants received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.

Administered by bolus injection into the venous line of the dialysis circuit at the end of hemodialysis treatment, and prior to or during rinse-back with each hemodialysis session (ie, 3 times per week).

This study is designed to describe the long-term safety and efficacy of etelcalcetide (AMG 416) for the treatment of SHPT in adults with CKD on hemodialysis.

Extension Study of Etelcalcetide in the Treatment of Secondary Hyperparathyroidism (SHPT) in Patients With Chronic Kidney Disease (CKD) on Hemodialysis

A Multicenter Single-arm Extension Study to Describe the Long-term Efficacy and Safety of AMG 416 in the Treatment of Secondary Hyperparathyroidism in Subjects With Chronic Kidney Disease on Hemodialysis

Treatment-related adverse events are those the investigator indicated as having a reasonable possibility of having been caused by etelcalcetide. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: • fatal • life threatening • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • congenital anomaly/birth defect • other medically important serious event.

Laboratory toxicity grading was based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, where Grade 0 represents values in the normal range and grade 4 represents values with life-threatening consequences and urgent intervention indicated.

A validated dual flow-cell biosensor immunoassay was used to detect antibodies capable of binding etelcalcetide. The number of participants with a negative or no result at baseline and positive binding antibodies at any time post-baseline is reported.

Blood pressure (BP) values were taken post-hemodialysis assessments.

The efficacy assessment phase (EAP) is defined as the last 6 weeks before ending treatment, which was only for participants who completed a minimum of 8 weeks of treatment with etelcalcetide. If multiple assessments were available during the EAP, values were averaged.

The efficacy assessment phase at 12 months (EAP12) was defined as the period from week 46 to 53 (inclusive). If multiple assessments were available during the EAP12, values were averaged.

Participants who received placebo in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.

20120229 / 20120230 Placebo

Participants who received etelcalcetide in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.

20120229 / 20120230 Etelcalcetide

Participants who received etelcalcetide in parent study 20120359 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.

20120359 Etelcalcetide

All participants received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks during the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.

Race/Ethnicity, Customized

600 - ≤ 1000 pg/mL

Parathyroid Hormone (PTH) Level

PTH Concentration

Any adverse event

Serious adverse events

Treatment-related adverse events

Treatment-related serious adverse events

AEs leading to discontinuation of etelcalcetide

Fatal adverse events

Etelcalcetide Total

All participants who received at least 1 dose of etelcalcetide.

Number of Participants With Adverse Events (AEs)

Alanine aminotransferase increase

Albumin decrease

Alkaline phosphatase increase

Aspartate aminotransferase increase

Bilirubin increase

Calcium (corrected) decrease

Calcium (corrected) increase

Phosphorus decrease

Potassium decrease

Potassium increase

Hemoglobin decrease

Hemoglobin increase

Number of Participants With Shift in Laboratory Values From Baseline Grade 0 or 1 to Post-baseline Grade 3 or 4

Participants who received at least 1 dose of etelcalcetide and with a post-baseline antibody result.

Number of Participants Who Developed Anti-etelcalcetide Antibodies

Participants with pre-dialysis PTH assessment at baseline and during the EAP who completed a minimum of 8 weeks of treatment with etelcalcetide.

Percentage of Participants With > 30% Reduction From Baseline in PTH During the Efficacy Assessment Phase

Participants with pre-dialysis PTH assessment at baseline and during EAP12

Percentage of Participants With > 30% Reduction From Baseline in PTH During the EAP12

Participants with predialysis PTH assessment during the EAP who completed a minimum of 8 weeks of treatment with etelcalcetide

Percentage of Participants With PTH ≤ 300 pg/mL During the EAP

Participants with predialysis PTH assessment during the EAP12

Percentage of Participants With PTH ≤ 300 pg/mL During the EAP12

Percent Change From Baseline in Mean PTH During the EAP

Percent Change From Baseline in Mean PTH During the EAP12

Percent Change From Baseline in Mean Corrected Calcium During the EAP

Percent Change From Baseline in Mean Corrected Calcium During the EAP12

Percent Change From Baseline in Mean Corrected Calcium Phosphorus Product During the EAP

Percent Change From Baseline in Mean Corrected Calcium Phosphorus Product During the EAP12

Percent Change From Baseline in Mean Phosphorus During the EAP

Percent Change From Baseline in Mean Phosphorus During the EAP12

Systolic BP Week 24 (n = 329, 342, 104, 775)

Systolic BP Week 48 (n = 305, 317, 74, 696)

Diastolic BP Week 24 (n = 329, 343, 104, 776)

Diastolic BP Week 48 (n = 305, 317, 74, 696)

Participants who received at least 1 dose of etelcalcetide and with available data at each time point (indicated by n)

Change From Baseline in Blood Pressure

Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session TIW for 26 weeks.

Administered intravenously three times per week. The starting dose was 5 mg. The dose may have been increased at weeks 5, 9, 13, and 17 (4-week intervals) by 2.5 mg or 5 mg on the basis of the predialysis parathyroid hormone and corrected calcium concentrations obtained in the prior week. The minimum dose was 2.5 mg and the maximum dose was 15 mg.

This study is designed to assess the efficacy and safety of etelcalcetide (AMG 416) compared with placebo in the treatment of SHPT in CKD patients receiving hemodialysis.

Efficacy and Safety of Etelcalcetide (AMG 416) in the Treatment of Secondary Hyperparathyroidism (SHPT) in Patients With Chronic Kidney Disease (CKD) on Hemodialysis

Stratification Factor: Screening Serum Parathroid Hormone

Data available for 257 and 251 participants in each treatment group respectively

Corrected Calcium (cCa)

A Cochran-Mantel-Haenszel test stratified by screening PTH category (\< 600, ≥ 600 to ≤ 1000, and \> 1000 pg/mL), recent cinacalcet use within 8 weeks before randomization (yes and no), and region (North America and non-North America) was used to compare the primary endpoint of percentage of participants with \> 30% reduction from baseline in PTH during the EAP between etelcalcetide and placebo.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy and Safety of Etelcalcetide (AMG 416) in the Treatment of Secondary Hyperparathyroidism (SHPT) in Patients With Chronic Kidney Disease on Hemodialysis	NCT01785849	Hyperparathyroi...	Etelcalcetide Placebo	18 Years - 100 Years	Amgen
Study to Assess the Impact on Calcium Levels When Hemodialysis Patients With Secondary Hyperparathyroidism (SHPT) Switch From Cinacalcet to Etelcalcetide	NCT01932970	Hyperparathyroi...	Etelcalcetide	18 Years - 100 Years	Amgen
Extension Study of Etelcalcetide in the Treatment of Secondary Hyperparathyroidism (SHPT) in Patients With Chronic Kidney Disease (CKD) on Hemodialysis	NCT01785875	Hyperparathyroi...	Etelcalcetide	18 Years - 100 Years	Amgen
Study to Assess the Impact on Calcium Levels When Hemodialysis Patients With Secondary Hyperparathyroidism (SHPT) Switch From Cinacalcet to Etelcalcetide	NCT01932970	Hyperparathyroi...	Etelcalcetide	18 Years - 100 Years	Amgen
Efficacy and Safety of Etelcalcetide (AMG 416) in the Treatment of Secondary Hyperparathyroidism (SHPT) in Patients With Chronic Kidney Disease (CKD) on Hemodialysis	NCT01788046	Hyperparathyroi...	Etelcalcetide Placebo	18 Years - 100 Years	Amgen
Efficacy and Safety of Etelcalcetide (AMG 416) in the Treatment of Secondary Hyperparathyroidism (SHPT) in Patients With Chronic Kidney Disease (CKD) on Hemodialysis	NCT01788046	Hyperparathyroi...	Etelcalcetide Placebo	18 Years - 100 Years	Amgen
Efficacy and Safety of Etelcalcetide (AMG 416) in the Treatment of Secondary Hyperparathyroidism (SHPT) in Patients With Chronic Kidney Disease (CKD) on Hemodialysis	NCT01788046	Hyperparathyroi...	Etelcalcetide Placebo	18 Years - 100 Years	Amgen
Efficacy and Safety of Etelcalcetide (AMG 416) in the Treatment of Secondary Hyperparathyroidism (SHPT) in Patients With Chronic Kidney Disease on Hemodialysis	NCT01785849	Hyperparathyroi...	Etelcalcetide Placebo	18 Years - 100 Years	Amgen

Spots Global Cancer Trial Database for secondary hyperparathyroidism (shpt), chronic kidney disease (ckd), hemodialysis, parathyroid hormone (pth), hypocalcemia, bone and mineral metabolism