Head-to-Head Study of Etelcalcetide and Cinacalcet in Asi... | NCT03299244

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cinacalcet	Active Comparator	Participants were randomized to receive oral cinacalcet once daily and placebo intravenous (IV) bolus injection at the end of each hemodialysis session three times per week (TIW) for 26 weeks. The starting dose of cinacalcet was 25 mg daily and the dose may have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum parathyroid hormone (PTH) ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining corrected calcium (cCa) ≥ 8.3 mg/dL.	Drug: Cinacalcet
Etelcalcetide	Experimental	Participants were randomized to receive etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session TIW and daily oral doses of placebo tablets for 26 weeks. The starting dose of etelcalcetide was 5 mg, and the dose may have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.	Drug: Etelcalcetide

Name	Type	Description	Arm Group Labels	Other Names
Etelcalcetide	Drug	Administered intravenously three times per week.	Etelcalcetide

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With > 30% Reduction From Baseline in Mean Predialysis Intact Parathyroid Hormone During the Efficacy Assessment Phase - Non-inferiority Analysis	Predialysis intact parathyroid hormone (iPTH) levels were measured by a central laboratory.	Baseline and the efficacy assessment phase (EAP; defined as weeks 20 to 27, inclusive).

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With > 50% Reduction From Baseline in Mean Predialysis iPTH During the Efficacy Assessment Phase	Predialysis intact parathyroid hormone levels were measured by a central laboratory.	Baseline and the efficacy assessment phase (weeks 20 to 27, inclusive).
Percentage of Participants With > 30% Reduction From Baseline in Mean Predialysis iPTH During the Efficacy Assessment Phase - Superiority Analysis

Other Outcomes

Measure	Description	Time Frame
Number of Participants With cCa < 8.3 mg/dL At Any Time During the Study	Corrected calcium was measured by the central laboratory.	From first dose of study drug to end of study; up to 26 weeks + 30 days.
Number of Participants With cCa < 8.0 mg/dL At Any Time During the Study

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subject has provided informed consent prior to performing any study-related activities/procedures.
Male or female subjects ≥ 18 years of age or older at the time of signing informed consent.
Subject must be receiving maintenance hemodialysis 3 times weekly for at least 3 months, with adequate hemodialysis based on a delivered measure of dialysis adequacy (Kt/V) ≥ 1.2 or urea reduction ratio ≥ 65% within 4 weeks prior to screening laboratory assessments. The Kt/V formula used for a subject must be the formula used during routine care prior to screening.
Dialysate calcium concentration must be ≥ 2.5 mEq/L (1.25 mmol/L) and stable for at least 4 weeks prior to screening laboratory assessments, and must remain ≥ 2.5 mEq/L (1.25 mmol/L) for the duration of the study.
Subject must have SHPT as defined by one central laboratory screening predialysis serum PTH value > 500 pg/mL, within 2 weeks prior to randomization.
Subject currently receiving vitamin D sterols must have had no more than a maximum dose change of 50% within the 4 weeks prior to screening laboratory assessments, remain stable through randomization, and be expected to maintain stable doses for the duration of the study, except for adjustments allowed per protocol or for safety reasons.
Subject must have 1 screening predialysis serum cCa laboratory value ≥ 8.3 mg/dL measured within 2 weeks prior to randomization.
A subject receiving calcium supplements must have had no more than a maximum dose change of 50% within 2 weeks prior to screening laboratory assessments and remain stable through randomization.
A subject receiving phosphate binders must have had no more than a maximum dose change of 50% within the 2 weeks prior to screening laboratory assessments, remain stable through randomization, and be expected to maintain stable dose for the duration of the study, except for adjustments allowed per protocol or for safety reasons.

Exclusion Criteria:

Currently receiving treatment in another investigational device or drug study, or ≤ 30 days since ending treatment on another investigational device or drug study(s). Other investigational procedures while participating in this study are excluded.
Subject has received etelcalcetide in a prior clinical trial of etelcalcetide.
Subject has received cinacalcet during the 3 months prior to the first screening laboratory assessments.
Subject has known sensitivity to any of the products or components of either cinacalcet or etelcalcetide to be administered during dosing.
Subject has previously been randomized in this study.
Anticipated or scheduled parathyroidectomy during the study period.
Subject has received a parathyroidectomy within 6 months prior to dosing.
Anticipated or scheduled kidney transplant during the study period.
Subject has an unstable medical condition based on medical history, physical examination, and routine laboratory tests, or is otherwise unstable in the judgment of the Investigator.
Malignancy within the last 5 years of screening (except non-melanoma skin cancers or cervical carcinoma in situ).
Grapefruit juice is prohibited.
Subject is pregnant or nursing, or planning to become pregnant or nurse during treatment or within 3 months after the last dose of etelcalcetide or 30 days after the last dose of cinacalcet
Female subject of childbearing potential who is unwilling to use an acceptable method of effective contraception during treatment with investigational product (IP) through 3 months after the last dose of IP.
Subject has a history of symptomatic ventricular dysrhythmias or Torsades de Pointes.
Subject has a history of myocardial infarction, coronary angioplasty, or coronary arterial bypass grafting within the past 6 months prior to screening.
Subject has clinically significant abnormalities on prestudy clinical examination or abnormalities on the most recent central laboratory tests during the screening period prior to randomization according to the Investigator including but not limited to the following:
- serum albumin < 3.0 g/dL
- serum magnesium < 1.5 mg/dL
- serum transaminase (alanine transaminase [ALT] or serum glutamic pyruvic transaminase [SGPT], aspartate aminotransferase [AST] or serum glutamic oxaloacetic transaminase [SGOT]) > 3 times the upper limit of normal (ULN) at screening.
Subject likely not available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and Investigator's knowledge.
History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the Investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.

Name	Affiliation	Role
MD	Amgen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Beijing	Beijing Municipality	100034	China
Research Site

Label	URL
AmgenTrials clinical trials website	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Cinacalcet	Participants were randomized to receive oral cinacalcet once daily and placebo intravenous (IV) bolus injection at the end of each hemodialysis session three times per week (TIW) for 26 weeks. The starting dose of cinacalcet was 25 mg daily and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 27, 2018	Apr 5, 2021

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00051.5± 12.9 BG00152.2± 13.4 BG00251.8± 13.1

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
18 - 64 years	BG000264 BG001262 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000138 BG001142 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Asian Indian	BG00019 BG00119 BG002

Stratification Factor: Screening Intact Parathyroid Hormone (iPTH)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
< 900 pg/mL	BG000128 BG001131 BG002

Stratification Factor: Screening Corrected Calcium (cCa)

When albumin was < 4.0 g/dL (40 g/L), the calcium level was corrected according to the following formula:

cCa (mg/dL) = total Ca (mg/dL) + (4 - albumin [g/dL]) x 0.8.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
< 9 mg/dL	BG00062 BG001

Stratification Factor: Country/Region

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
China	BG000189 BG001191 BG002

Intact Parathyroid Hormone Level

Mean

Standard Deviation

pg/mL

Title

Denominators

Categories

Title	Measurements
	BG0001299.01± 830.99 BG0011299.91± 853.82 BG002

Corrected Calcium Level

Mean

Standard Deviation

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG0009.71± 0.75 BG0019.73± 0.90 BG002

Phosphorus Level

Mean

Standard Deviation

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG0006.67± 1.61 BG0016.62± 1.55 BG002

Corrected Calcium Phosphorus Product (cCa x P)

Mean

Standard Deviation

mg²/dL²

Title

Denominators

Categories

Title	Measurements
	BG00064.70± 16.39 BG00164.41± 16.33 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With > 30% Reduction From Baseline in Mean Predialysis Intact Parathyroid Hormone During the Efficacy Assessment Phase - Non-inferiority Analysis

Predialysis intact parathyroid hormone (iPTH) levels were measured by a central laboratory.

Full analysis set; participants with iPTH data during the EAP.

Posted

Number

percentage of participants

Baseline and the efficacy assessment phase (EAP; defined as weeks 20 to 27, inclusive).

ID	Title	Description
OG000	Cinacalcet	Participants were randomized to receive oral cinacalcet once daily and placebo intravenous (IV) bolus injection at the end of each hemodialysis session three times per week (TIW) for 26 weeks. The starting dose of cinacalcet was 25 mg daily and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.
OG001	Etelcalcetide	Participants were randomized to receive etelcalcetide administered by IV bolus injection at the end of each hemodialysis session TIW and daily oral doses of placebo tablets for 26 weeks. The starting dose of etelcalcetide was 5 mg, and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.

Units	Counts
Participants	OG000278 OG001295

Title

Denominators

Categories

Title	Measurements
	OG00066.2 OG00171.9

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The analysis was conducted on the full analysis set (637 participants). Imputation under the non-inferiority null method was applied to participants who did not have PTH data during the EAP. The Mantel-Haenszel estimator was used to calculate the treatment (Cinacalcet - Etelcalcetide), stratified by screening PTH level (< 900 pg/mL, ≥ 900 pg/mL), screening serum cCa (< 9.0 mg/dL, ≥ 9.0 mg/dL) measured by the central laboratory, and country (China versus non-China).					Treatment Difference	4.52			2-Sided	95	-3.05	12.09			Treatment difference (Etelcalcetide - Cinacalcet) stratified by screening iPTH level, screening cCa level, and country/region.

Secondary

Percentage of Participants With > 50% Reduction From Baseline in Mean Predialysis iPTH During the Efficacy Assessment Phase

Predialysis intact parathyroid hormone levels were measured by a central laboratory.

Full analysis set; participants were considered non-responders if they did not have PTH data during the EAP (non-responder imputation).

Posted

Number

percentage of participants

Baseline and the efficacy assessment phase (weeks 20 to 27, inclusive).

ID	Title	Description
OG000	Cinacalcet	Participants were randomized to receive oral cinacalcet once daily and placebo intravenous (IV) bolus injection at the end of each hemodialysis session three times per week (TIW) for 26 weeks. The starting dose of cinacalcet was 25 mg daily and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.
OG001	Etelcalcetide	Participants were randomized to receive etelcalcetide administered by IV bolus injection at the end of each hemodialysis session TIW and daily oral doses of placebo tablets for 26 weeks. The starting dose of etelcalcetide was 5 mg, and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.

Secondary

Percentage of Participants With > 30% Reduction From Baseline in Mean Predialysis iPTH During the Efficacy Assessment Phase - Superiority Analysis

Predialysis intact parathyroid hormone levels were measured by a central laboratory.

Full analysis set; participants were considered non-responders if they did not have PTH data during the EAP.

Posted

Number

percentage of participants

Baseline and the efficacy assessment phase (weeks 20 to 27, inclusive)

ID	Title	Description
OG000	Cinacalcet	Participants were randomized to receive oral cinacalcet once daily and placebo intravenous (IV) bolus injection at the end of each hemodialysis session three times per week (TIW) for 26 weeks. The starting dose of cinacalcet was 25 mg daily and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.
OG001	Etelcalcetide	Participants were randomized to receive etelcalcetide administered by IV bolus injection at the end of each hemodialysis session TIW and daily oral doses of placebo tablets for 26 weeks. The starting dose of etelcalcetide was 5 mg, and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.

Secondary

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

Predialysis corrected calcium was measured by a central laboratory.

Full analysis set; participants with available data

Posted

Mean

Standard Error

percent change

Baseline and the efficacy assessment phase (weeks 20 - 27, inclusive)

ID	Title	Description
OG000	Cinacalcet	Participants were randomized to receive oral cinacalcet once daily and placebo intravenous (IV) bolus injection at the end of each hemodialysis session three times per week (TIW) for 26 weeks. The starting dose of cinacalcet was 25 mg daily and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.
OG001	Etelcalcetide	Participants were randomized to receive etelcalcetide administered by IV bolus injection at the end of each hemodialysis session TIW and daily oral doses of placebo tablets for 26 weeks. The starting dose of etelcalcetide was 5 mg, and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.

Units

Secondary

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

Predialysis serum phosphorus was measured by a central laboratory.

Full analysis set; participants with no phosphorus assessments during the EAP were considered non-responders.

Posted

Number

percentage of participants

Efficacy assessment phase (weeks 20 - 27, inclusive)

ID	Title	Description
OG000	Cinacalcet	Participants were randomized to receive oral cinacalcet once daily and placebo intravenous (IV) bolus injection at the end of each hemodialysis session three times per week (TIW) for 26 weeks. The starting dose of cinacalcet was 25 mg daily and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.
OG001	Etelcalcetide	Participants were randomized to receive etelcalcetide administered by IV bolus injection at the end of each hemodialysis session TIW and daily oral doses of placebo tablets for 26 weeks. The starting dose of etelcalcetide was 5 mg, and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.

Other Pre-specified

Number of Participants With cCa < 8.3 mg/dL At Any Time During the Study

Corrected calcium was measured by the central laboratory.

Participants in the safety analysis set with at least 1 post-baseline cCa value.

The safety analysis set includes all randomized participants who received at least 1 dose of study drug.

Posted

Count of Participants

Participants

From first dose of study drug to end of study; up to 26 weeks + 30 days.

ID	Title	Description
OG000	Cinacalcet	Participants were randomized to receive oral cinacalcet once daily and placebo intravenous (IV) bolus injection at the end of each hemodialysis session three times per week (TIW) for 26 weeks. The starting dose of cinacalcet was 25 mg daily and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.
OG001	Etelcalcetide	Participants were randomized to receive etelcalcetide administered by IV bolus injection at the end of each hemodialysis session TIW and daily oral doses of placebo tablets for 26 weeks. The starting dose of etelcalcetide was 5 mg, and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.

Other Pre-specified

Number of Participants With cCa < 8.0 mg/dL At Any Time During the Study

Corrected calcium was measured by the central laboratory.

Participants in the safety analysis set with at least 1 post-baseline cCa value.

Posted

Count of Participants

Participants

From first dose of study drug to end of study; up to 26 weeks + 30 days.

ID	Title	Description
OG000	Cinacalcet	Participants were randomized to receive oral cinacalcet once daily and placebo intravenous (IV) bolus injection at the end of each hemodialysis session three times per week (TIW) for 26 weeks. The starting dose of cinacalcet was 25 mg daily and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.
OG001	Etelcalcetide	Participants were randomized to receive etelcalcetide administered by IV bolus injection at the end of each hemodialysis session TIW and daily oral doses of placebo tablets for 26 weeks. The starting dose of etelcalcetide was 5 mg, and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.

Units

Other Pre-specified

Number of Participants With cCa < 7.5 mg/dL At Any Time During the Study

Corrected calcium was measured by the central laboratory.

Participants in the safety analysis set with at least 1 post-baseline cCa value.

Posted

Count of Participants

Participants

From first dose of study drug to end of study; up to 26 weeks + 30 days.

ID	Title	Description
OG000	Cinacalcet	Participants were randomized to receive oral cinacalcet once daily and placebo intravenous (IV) bolus injection at the end of each hemodialysis session three times per week (TIW) for 26 weeks. The starting dose of cinacalcet was 25 mg daily and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.
OG001	Etelcalcetide	Participants were randomized to receive etelcalcetide administered by IV bolus injection at the end of each hemodialysis session TIW and daily oral doses of placebo tablets for 26 weeks. The starting dose of etelcalcetide was 5 mg, and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.

Units

Other Pre-specified

Number of Participants With Treatment-emergent Symptomatic Hypocalcemia During the Study

Common symptoms of hypocalcemia (diminished blood calcium) include paresthesias (fingertips, toes, or perioral), fatigue, muscle cramps, irritability or anxiety, tetany (eg, carpopedal spasm, laryngospasm), Chvostek's sign, seizures, and prolonged QT interval.

Safety analysis set

Posted

Count of Participants

Participants

From first dose of study drug to 30 days after last dose; up to 26 weeks + 30 days.

ID	Title	Description
OG000	Cinacalcet	Participants were randomized to receive oral cinacalcet once daily and placebo intravenous (IV) bolus injection at the end of each hemodialysis session three times per week (TIW) for 26 weeks. The starting dose of cinacalcet was 25 mg daily and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.
OG001	Etelcalcetide	Participants were randomized to receive etelcalcetide administered by IV bolus injection at the end of each hemodialysis session TIW and daily oral doses of placebo tablets for 26 weeks. The starting dose of etelcalcetide was 5 mg, and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.

Other Pre-specified

Number of Participants Who Developed Antibodies to Etelcalcetide

Developing antibody incidence is defined as participants who were binding antibody positive post-baseline with a negative or no result at baseline.

Safety analysis set participants assigned to etelcalcetide with a post-baseline antibody result.

Posted

Count of Participants

Participants

From first dose of study drug to 30 days after last dose; up to 26 weeks + 30 days.

ID	Title	Description
OG000	Etelcalcetide	Participants were randomized to receive etelcalcetide administered by IV bolus injection at the end of each hemodialysis session TIW and daily oral doses of placebo tablets for 26 weeks. The starting dose of etelcalcetide was 5 mg, and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.

Units	Counts
Participants	OG000

Other Pre-specified

Number of Participants With Treatment-emergent Adverse Events

An adverse event is defined as any untoward medical occurrence in a clinical study participant, including worsening of a pre-existing medical condition. The event does not necessarily have a causal relationship with study treatment. The investigator assessed whether each adverse event was possibly related to study drug.

A serious adverse event is defined as an adverse event that met at least 1 of the following serious criteria:

fatal
life threatening
required in-patient hospitalization or prolongation of existing hospitalization
resulted in persistent or significant disability/incapacity
congenital anomaly/birth defect
other medically important serious event

Safety analysis set

Posted

Count of Participants

Participants

From first dose of study drug to 30 days after last dose; up to 26 weeks + 30 days.

ID	Title	Description
OG000	Cinacalcet	Participants were randomized to receive oral cinacalcet once daily and placebo intravenous (IV) bolus injection at the end of each hemodialysis session three times per week (TIW) for 26 weeks. The starting dose of cinacalcet was 25 mg daily and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.
OG001	Etelcalcetide	Participants were randomized to receive etelcalcetide administered by IV bolus injection at the end of each hemodialysis session TIW and daily oral doses of placebo tablets for 26 weeks. The starting dose of etelcalcetide was 5 mg, and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Granulocytopenia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Microcytic anaemia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0003 affected315 at risk EG0010 affected318 at risk
Angina pectoris	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0011 affected318 at risk
Angina unstable	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Aortic valve incompetence	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Arteriosclerosis coronary artery	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected315 at risk EG0010 affected318 at risk
Cardiac arrest	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Cardiac failure	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0011 affected318 at risk
Cardiac failure acute	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected315 at risk EG0012 affected318 at risk
Cardiogenic shock	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Cardiovascular disorder	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Coronary artery disease	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected315 at risk EG0010 affected318 at risk
Hypertensive heart disease	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0011 affected318 at risk
Sinus node dysfunction	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Ventricular extrasystoles	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Ventricular fibrillation	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Hyperparathyroidism secondary	Endocrine disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0011 affected318 at risk
Cataract	Eye disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected315 at risk EG0010 affected318 at risk
Colitis ischaemic	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Gastric ulcer haemorrhage	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Ileus	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Death	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Impaired healing	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Pyrexia	General disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0011 affected318 at risk
Sudden cardiac death	General disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0011 affected318 at risk
Jaundice cholestatic	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Anal abscess	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Bacteraemia	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Bacterial sepsis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Bronchitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0012 affected318 at risk
Complicated appendicitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Device related infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Device related sepsis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Diarrhoea infectious	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Endocarditis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Febrile infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Infective aneurysm	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Influenza	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Peritonitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0002 affected315 at risk EG0011 affected318 at risk
Pneumonia	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0004 affected315 at risk EG0017 affected318 at risk
Pyelonephritis acute	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Rectal abscess	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Urinary tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Arteriovenous fistula occlusion	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0003 affected315 at risk EG0015 affected318 at risk
Arteriovenous fistula site complication	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0002 affected315 at risk EG0011 affected318 at risk
Arteriovenous fistula thrombosis	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0012 affected318 at risk
Coronary artery restenosis	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Ilium fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Ligament rupture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Shunt malfunction	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Ulna fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Vascular access complication	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Vascular access malfunction	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Transplant evaluation	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Fracture malunion	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected315 at risk EG0011 affected318 at risk
Cerebral infarction	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Encephalopathy	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Jugular vein occlusion	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Lacunar infarction	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected315 at risk EG0011 affected318 at risk
Speech disorder	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Subarachnoid haemorrhage	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Uraemic encephalopathy	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Device malfunction	Product Issues	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Sleep disorder	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Azotaemia	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0012 affected318 at risk
End stage renal disease	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected315 at risk EG0013 affected318 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0011 affected318 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Diabetic foot	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Arteriovenous fistula operation	Surgical and medical procedures	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Jejunostomy	Surgical and medical procedures	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Granulomatosis with polyangiitis	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Hypertension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0014 affected318 at risk
Hypotension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0011 affected318 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected315 at risk EG0010 affected318 at risk
Peripheral artery occlusion	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Peripheral ischaemia	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected315 at risk EG0011 affected318 at risk
Subclavian vein stenosis	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk
Thrombosis	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected315 at risk EG0010 affected318 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal discomfort	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG00017 affected315 at risk EG00115 affected318 at risk
Constipation	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG00012 affected315 at risk EG00118 affected318 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG00014 affected315 at risk EG00119 affected318 at risk
Nausea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG00045 affected315 at risk EG00135 affected318 at risk
Vomiting	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG00047 affected315 at risk EG00130 affected318 at risk
Chest discomfort	General disorders	MedDRA 23.0	Systematic Assessment	EG00016 affected315 at risk EG00115 affected318 at risk
Nasopharyngitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG00031 affected315 at risk EG00128 affected318 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG00033 affected315 at risk EG00134 affected318 at risk
Blood calcium decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG000218 affected315 at risk EG001252 affected318 at risk
Blood calcium increased	Investigations	MedDRA 23.0	Systematic Assessment	EG00016 affected315 at risk EG00116 affected318 at risk
Blood pressure increased	Investigations	MedDRA 23.0	Systematic Assessment	EG00018 affected315 at risk EG00112 affected318 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG00018 affected315 at risk EG00110 affected318 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG00017 affected315 at risk EG00112 affected318 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG00013 affected315 at risk EG00119 affected318 at risk
Hyperphosphataemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG00034 affected315 at risk EG00126 affected318 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG00015 affected315 at risk EG00135 affected318 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG00017 affected315 at risk EG0017 affected318 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG00037 affected315 at risk EG00148 affected318 at risk
Dizziness	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG00024 affected315 at risk EG00128 affected318 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0008 affected315 at risk EG00122 affected318 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG00029 affected315 at risk EG00123 affected318 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG00013 affected315 at risk EG00116 affected318 at risk
Dialysis hypotension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG00011 affected315 at risk EG00118 affected318 at risk
Hypertension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG00018 affected315 at risk EG00116 affected318 at risk
Hypotension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG00027 affected315 at risk EG00134 affected318 at risk

ID	Term
D006962	Hyperparathyroidism, Secondary
D051436	Renal Insufficiency, Chronic

ID	Term
D006961	Hyperparathyroidism
D010279	Parathyroid Diseases
D004700	Endocrine System Diseases
D051437	Renal Insufficiency
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D009281	Naphthalenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D011083	Polycyclic Compounds

ID	Title	Description
BG000	Cinacalcet	Participants were randomized to receive oral cinacalcet once daily and placebo intravenous (IV) bolus injection at the end of each hemodialysis session three times per week (TIW) for 26 weeks. The starting dose of cinacalcet was 25 mg daily and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.
BG001	Etelcalcetide	Participants were randomized to receive etelcalcetide administered by IV bolus injection at the end of each hemodialysis session TIW and daily oral doses of placebo tablets for 26 weeks. The starting dose of etelcalcetide was 5 mg, and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cinacalcet	Participants were randomized to receive oral cinacalcet once daily and placebo intravenous (IV) bolus injection at the end of each hemodialysis session three times per week (TIW) for 26 weeks. The starting dose of cinacalcet was 25 mg daily and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.	9	317	61	315	293	315
EG001	Etelcalcetide	Participants were randomized to receive etelcalcetide administered by IV bolus injection at the end of each hemodialysis session TIW and daily oral doses of placebo tablets for 26 weeks. The starting dose of etelcalcetide was 5 mg, and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.	4	320	53	318	294	318