Secondary Hyperparathyroidism
Conditions
Keywords
Secondary hyperparathyroidism, Chronic kidney disease CKD, Intact parathyroid hormone iPTH, Hemodialysis
Brief summary
This was a multiple-dose, double-blind, randomized, placebo-controlled study. Chinese subjects residing in Mainland China with chronic kidney disease (CKD) receiving hemodialysis were randomized in a 3:1 ratio to receive 5 mg intravenous (IV) of etelcalcetide or placebo 3 times a week (TIW) for approximately 4 weeks, with a subsequent follow up period of approximately 4 weeks. Doses were given at the end of each scheduled hemodialysis session on study days 1 through day 27 and subject participation was complete after day 55 end-of-study (EOS) procedures were performed. Doses were administered TIW for 4 weeks, for a total of 12 doses.
Interventions
DRUGEtelcalcetide
Etelcalcetide was supplied as a sterile, preservative-free, aqueous solution in a single-use 3 mL glass vial.
DRUGPlacebo
Placebo supplied to match active intervention.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
This is a multiple dose, double-blind, randomized, placebo-controlled clinical study conducted in Chinese subjects residing in Mainland China with chronic kidney disease receiving hemodialysis. The treatment duration will be approximately 4 weeks with a post treatment followup of 4 weeks. A dose will be given at each scheduled hemodialysis session (Dose administered three times a week for 4 weeks, for a total of 12 doses).
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Subject has provided informed consent prior to initiation of any study-specific activities/procedures * Resident in Mainland China and of Chinese ancestry * Male or female subject ≥ 18 and ≤ 70 years of age at the time of screening, with end stage renal disease receiving hemodialysis * Subject must be receiving hemodialysis 3 times weekly for at least 3 months through a functioning permanent dialysis access prior to Day -2 and have adequate hemodialysis with a delivered Kt/V ≥ 1.2 or urea reduction ratio (URR) ≥ 65% within 4 weeks to screening. The subject's routine hemodialysis session must be of 3-4.5 hours in duration, inclusive * Subject has stable dialysis prescription and this prescription is not anticipated to significantly change during the course of the study
Exclusion criteria
* Corrected calcium (calculated) level is \< 2.07 mmol/L (8.3 mg/dL), and/or intact PTH level is outside the range of 31.8 - 127.3 pmol/L (300 - 1200 pg/mL) * Female subjects who are pregnant, lactating/breastfeeding, or who plan to conceive, or breastfeed while on study through 3 months after receiving the dose of study drug * Female subject of reproductive potential not willing to use a(n) acceptable method(s) of effective birth control during treatment with AMG 416, and for an additional 3 months after the end of treatment with AMG 416. Female subjects who have had a hysterectomy, bilateral salpingectomy, bilateral oophorectomy, bilateral tubal ligation, or who are postmenopausal are not required to use contraception. Postmenopausal is defined as: * Age \> 55 years with cessation of menses for 12 months or more * Age \< 55 but no spontaneous menses for at least 2 years * Age \< 55 years and spontaneous menses within the past 1 years, but currently amenorrheic, AND with postmenopausal gonadrotropin levels (luteinizing hormone and follicle-stimulating hormone levels \> 40 IU/L) or postmenopausal estradiol levels (\<5.3 pmol/L or 5 ng/dL) or according to the definition of postmenopausal range for the laboratory involved * Underwent a bilateral oophorectomy * Females of reproductive potential with a positive pregnancy test, unless medical follow-up confirms the subject is not pregnant * Previous administration of AMG 416 * Subject has received cinacalcet within the 30 days prior to informed consent (treatment with cinacalcet is prohibited during the study) * Subject has lost 500 mL or more of blood or plasma within 8 weeks of study drug administration or during the study period * Anticipated or scheduled to have major surgical procedures during the study period such as kidney transplant or parathyroidectomy * History of malignancy within 5 years before Day -2 (except non melanoma skin cancers, or cervical carcinoma in situ) * Subject's 12-lead electrocardiogram (ECG) at screening suggests unstable arrhythmia or other cardiac abnormality that could place the subject at increased risk, based upon the Investigator's opinion * Subject has current or history of cardiovascular conditions such as uncontrolled hypertension, symptomatic ventricular dysrhythmias, Torsades de Pointes, angina pectoris congestive heart failure (New York Heart Association Classification III or IV), myocardial infarction, coronary angioplasty, or coronary arterial bypass grafting within the past 6 months prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Parameter: Time to Maximum Drug Concentration (Tmax) of Plasma Etelcalcetide on Days 1 and 27 | Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administration | Tmax is the time to maximum drug concentration of plasma etelcalcetide after dosing on Days 1 and 27. |
| PK: Maximum Observed Drug Concentration (Cmax) of Plasma Etelcalcetide on Days 1 and 27 | Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administration | Cmax was defined as the maximum observed plasma drug concentration measured between the time of drug administration to the beginning of the next dialysis session. |
| Pharmacokinetic (PK) Parameter: Area Under the Curve From Time Zero to the Beginning of the Subsequent Hemodialysis Treatment (AUClast) of Plasma Etelcalcetide on Days 1 and 27 | Days 1 and 27; PK blood sampling predialysis, and up to 44-50 hour postdose.at 10, 30, 60, 90 min postdose: Day 2 and 28 between 18 and 30 hours after study drug administration; Day 3 (predialysis) + Day 29 | AUClast was specifically defined in this study as the area under the concentration time curve measured from the time of drug administration to the beginning of the next dialysis session, following the first and last dose. |
| Pharmacokinetic (PK) Parameter: Accumulation Ratio Comparing Days 1 and 27 | Days 1 and 27; PK blood sampling predialysis, and up to 44-50 hour postdose.at 10, 30, 60, 90 min postdose: Day 2 and 28 between 18 and 30 hours after study drug administration; Day 3 (predialysis) + Day 29 | Accumulation ratio, calculated as AUClast day 27/AUClast day 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to End of Study in Systolic and Diastolic Blood Pressures | Baseline Day 1 prior to dialysis; End of Study is Day 55 | Participants remained seated for at least 10 minutes prior to measurement of predialysis heart rate and blood pressure. |
| Baseline and Change From Baseline to End of Study in Heart Rate | Baseline Day 1 prior to dialysis; End of Study is Day 55 | Participants remained seated for at least 10 minutes prior to measurement of predialysis heart rate and blood pressure. |
| Change From Baseline to End of Study in Calcium | Baseline is Day 1 prior to dialysis; End of Study is Day 55 | Calcium was tested at a central laboratory. |
| Change From Baseline to End of Study in Corrected Calcium (cCa) | Baseline is the average of Day -2 and Day 1 prior to dialysis; End of Study is Day 55 | Total serum calcium was corrected if the serum albumin was \< 4 g/dL or 40 g/L, otherwise cCa equals total serum calcium. The correction formula was: Corrected calcium (mg/dL) = Total calcium (mg/dL) + (4 - albumin \[g/dL\]) \* 0.8 |
| Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Day 1 up to Day 55 (end of study) | Terms were coded with Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. Narrow search criteria used for both standardized MedDRA queries (SMQ) and events of interest (EOI). One preferred term (PT) could match multiple EOIs. Infusion Reaction EOI counts included only those events which had onset day coinciding with study medication infusion and resolved on the same day or the day after onset. |
| Baseline and Change From Baseline to End of Study in Serum Albumin | Baseline is the average of Day -2 and Day 1 prior to dialysis; End of Study is Day 55 | Serum albumin was tested at a central laboratory. |
| Change From Baseline to End of Study in Serum Phosphorus | Baseline is Day 1 prior to dialysis; End of Study is Day 55 | Serum phosphorus was tested at a central laboratory. |
| Participants With Anti-etelcalcetide Antibody at Baseline and Postbaseline | Baseline: Day 1 prior to dialysis. Postbaseline: Days 29 and 55 prior to dialysis | Participants with positive titers for antibodies to etelcalcetide could be asked to return to the clinical research unit to provide additional serum samples. |
| Participants With Low Corrected Calcium (cCA) By Category | Timeframes: Days 8, 15, 22, 27, 29, 34, 41, 55 | The lowest cCA value for each participant is reported. Total serum calcium was corrected if the serum albumin was \< 4 g/dL or 40 g/L, otherwise cCa equals total serum calcium. The correction formula was: Corrected calcium (mg/dL) = Total calcium (mg/dL) + (4 - albumin \[g/dL\]) \* 0.8 |
| Participants With Treatment-Emergent Adverse Events (TEAEs) | Day 1 up to Day 55 (end of study) | The severity of each adverse event was assessed using the NCI-CTCAE Version 4.0 according to the following: * Grade 1 - Mild: Asymptomatic or mild symptoms; intervention not indicated * Grade 2 - Moderate: Minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL) * Grade 3 - Severe: Medically significant but not life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL * Grade 4 - Life-threatening * Grade 5 - Fatal. A serious AE is an AE that met one or more of the following criteria: * Death * Life-threatening * Required inpatient hospitalization or prolongation of an existing hospitalization * Resulted in persistent or significant disability/incapacity * A congenital anomaly/birth defect * Important medical events that required medical or surgical intervention to prevent one of the outcomes above. |
| Participants With Clinically-Significant Changes in Electrocardiograms (ECGs) From Baseline to End of Study | Baseline is Day -2; End of Study is Day 55 | Count of participants who exhibited a clinically significant change in the results of their 12-lead electrocardiograms (ECG) when comparing baseline to end of study ECGs. |
| Change From Baseline to End of Study in Weight | Day 1 up to Day 55 | Change from baseline in weight measured at visit. |
Countries
China
Participant flow
Recruitment details
This study was conducted at 5 centers in China.
Pre-assignment details
Of the 37 subjects screened, 33 participants were randomized in a 3:1 ratio to either etelcalcetide or placebo in a double-blind manner prior to the Day 1 activities.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks. | 8 |
| Etelcalcetide 5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks. | 25 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Etelcalcetide | Total |
|---|---|---|---|
| Age, Continuous | 49.8 years STANDARD_DEVIATION 12.5 | 50.2 years STANDARD_DEVIATION 11.4 | 50.1 years STANDARD_DEVIATION 11.5 |
| Body Mass Index (BMI) | 23.64 kg/m^2 STANDARD_DEVIATION 3.03 | 24.98 kg/m^2 STANDARD_DEVIATION 4.03 | 24.65 kg/m^2 STANDARD_DEVIATION 3.81 |
| Calcium | 2.57 mmol/L STANDARD_DEVIATION 0.14 | 2.44 mmol/L STANDARD_DEVIATION 0.22 | 2.47 mmol/L STANDARD_DEVIATION 0.21 |
| Corrected Calcium | 2.57 mmol/L STANDARD_DEVIATION 0.12 | 2.46 mmol/L STANDARD_DEVIATION 0.2 | 2.49 mmol/L STANDARD_DEVIATION 0.19 |
| Diastolic Blood Pressure | 80.38 mmHg STANDARD_DEVIATION 13.54 | 81.68 mmHg STANDARD_DEVIATION 13 | 81.36 mmHg STANDARD_DEVIATION 12.93 |
| Height | 167.54 cm STANDARD_DEVIATION 8.17 | 164.48 cm STANDARD_DEVIATION 7.68 | 165.22 cm STANDARD_DEVIATION 7.79 |
| Intact Parathyroid Hormone (iPTH) | 74.10 pmol/L STANDARD_DEVIATION 35.08 | 63.03 pmol/L STANDARD_DEVIATION 20.1 | 65.72 pmol/L STANDARD_DEVIATION 24.4 |
| Phosphorus | 2.17 mmol/L STANDARD_DEVIATION 0.49 | 2.11 mmol/L STANDARD_DEVIATION 0.58 | 2.13 mmol/L STANDARD_DEVIATION 0.55 |
| Potassium | 4.67 mmol/L STANDARD_DEVIATION 0.48 | 4.74 mmol/L STANDARD_DEVIATION 0.8 | 4.72 mmol/L STANDARD_DEVIATION 0.73 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 25 Participants | 33 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 3 Participants | 10 Participants | 13 Participants |
| Sex: Female, Male Male | 5 Participants | 15 Participants | 20 Participants |
| Systolic Blood Pressure | 139.25 mmHg STANDARD_DEVIATION 27.37 | 141.24 mmHg STANDARD_DEVIATION 19.39 | 140.76 mmHg STANDARD_DEVIATION 21.13 |
| Weight | 65.74 kg STANDARD_DEVIATION 8.45 | 67.71 kg STANDARD_DEVIATION 13.53 | 67.24 kg STANDARD_DEVIATION 12.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 25 |
| other Total, other adverse events | 7 / 8 | 22 / 25 |
| serious Total, serious adverse events | 0 / 8 | 3 / 25 |
Outcome results
Primary
Pharmacokinetic (PK) Parameter: Accumulation Ratio Comparing Days 1 and 27
Accumulation ratio, calculated as AUClast day 27/AUClast day 1.
Time frame: Days 1 and 27; PK blood sampling predialysis, and up to 44-50 hour postdose.at 10, 30, 60, 90 min postdose: Day 2 and 28 between 18 and 30 hours after study drug administration; Day 3 (predialysis) + Day 29
Population: Pharmacokinetic concentration analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etelcalcetide | Pharmacokinetic (PK) Parameter: Accumulation Ratio Comparing Days 1 and 27 | 3.02 ratio | Standard Deviation 0.607 |
Primary
Pharmacokinetic (PK) Parameter: Area Under the Curve From Time Zero to the Beginning of the Subsequent Hemodialysis Treatment (AUClast) of Plasma Etelcalcetide on Days 1 and 27
AUClast was specifically defined in this study as the area under the concentration time curve measured from the time of drug administration to the beginning of the next dialysis session, following the first and last dose.
Time frame: Days 1 and 27; PK blood sampling predialysis, and up to 44-50 hour postdose.at 10, 30, 60, 90 min postdose: Day 2 and 28 between 18 and 30 hours after study drug administration; Day 3 (predialysis) + Day 29
Population: Pharmacokinetic concentration analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Etelcalcetide | Pharmacokinetic (PK) Parameter: Area Under the Curve From Time Zero to the Beginning of the Subsequent Hemodialysis Treatment (AUClast) of Plasma Etelcalcetide on Days 1 and 27 | Day 1 | 1110 hour*ng/mL | Standard Deviation 311 |
| Etelcalcetide | Pharmacokinetic (PK) Parameter: Area Under the Curve From Time Zero to the Beginning of the Subsequent Hemodialysis Treatment (AUClast) of Plasma Etelcalcetide on Days 1 and 27 | Day 27 | 3310 hour*ng/mL | Standard Deviation 893 |
Primary
Pharmacokinetic (PK) Parameter: Time to Maximum Drug Concentration (Tmax) of Plasma Etelcalcetide on Days 1 and 27
Tmax is the time to maximum drug concentration of plasma etelcalcetide after dosing on Days 1 and 27.
Time frame: Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administration
Population: Pharmacokinetic Concentration Analysis Set: all participants who received at least 1 dose of etelcalcetide and had at least 1 pharmacokinetic sample collected.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Etelcalcetide | Pharmacokinetic (PK) Parameter: Time to Maximum Drug Concentration (Tmax) of Plasma Etelcalcetide on Days 1 and 27 | Day 1 | 0.22 hour |
| Etelcalcetide | Pharmacokinetic (PK) Parameter: Time to Maximum Drug Concentration (Tmax) of Plasma Etelcalcetide on Days 1 and 27 | Day 27 | 0.22 hour |
Primary
PK: Maximum Observed Drug Concentration (Cmax) of Plasma Etelcalcetide on Days 1 and 27
Cmax was defined as the maximum observed plasma drug concentration measured between the time of drug administration to the beginning of the next dialysis session.
Time frame: Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administration
Population: Pharmacokinetic concentration analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Etelcalcetide | PK: Maximum Observed Drug Concentration (Cmax) of Plasma Etelcalcetide on Days 1 and 27 | Day 1 | 216 ng/mL | Standard Deviation 157 |
| Etelcalcetide | PK: Maximum Observed Drug Concentration (Cmax) of Plasma Etelcalcetide on Days 1 and 27 | Day 27 | 236 ng/mL | Standard Deviation 53.7 |
Secondary
Baseline and Change From Baseline to End of Study in Heart Rate
Participants remained seated for at least 10 minutes prior to measurement of predialysis heart rate and blood pressure.
Time frame: Baseline Day 1 prior to dialysis; End of Study is Day 55
Population: Safety Analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Baseline and Change From Baseline to End of Study in Heart Rate | Baseline | 79.5 beats/minute | Standard Deviation 8.3 |
| Placebo | Baseline and Change From Baseline to End of Study in Heart Rate | Change from Baseline to End of Study | -2.9 beats/minute | Standard Deviation 6.5 |
| Etelcalcetide | Baseline and Change From Baseline to End of Study in Heart Rate | Baseline | 82.8 beats/minute | Standard Deviation 13.8 |
| Etelcalcetide | Baseline and Change From Baseline to End of Study in Heart Rate | Change from Baseline to End of Study | -1.4 beats/minute | Standard Deviation 8.9 |
Secondary
Baseline and Change From Baseline to End of Study in Serum Albumin
Serum albumin was tested at a central laboratory.
Time frame: Baseline is the average of Day -2 and Day 1 prior to dialysis; End of Study is Day 55
Population: Safety Analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Baseline and Change From Baseline to End of Study in Serum Albumin | Baseline | 41.20 g/dL | Standard Deviation 2.37 |
| Placebo | Baseline and Change From Baseline to End of Study in Serum Albumin | Change from Baseline to End of Study | -1.06 g/dL | Standard Deviation 1.81 |
| Etelcalcetide | Baseline and Change From Baseline to End of Study in Serum Albumin | Baseline | 39.37 g/dL | Standard Deviation 2.79 |
| Etelcalcetide | Baseline and Change From Baseline to End of Study in Serum Albumin | Change from Baseline to End of Study | -0.59 g/dL | Standard Deviation 2.13 |
Secondary
Change From Baseline to End of Study in Calcium
Calcium was tested at a central laboratory.
Time frame: Baseline is Day 1 prior to dialysis; End of Study is Day 55
Population: Safety Analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Study in Calcium | -0.10 mmol/L | Standard Deviation 0.11 |
| Etelcalcetide | Change From Baseline to End of Study in Calcium | -0.07 mmol/L | Standard Deviation 0.12 |
Secondary
Change From Baseline to End of Study in Corrected Calcium (cCa)
Total serum calcium was corrected if the serum albumin was \< 4 g/dL or 40 g/L, otherwise cCa equals total serum calcium. The correction formula was: Corrected calcium (mg/dL) = Total calcium (mg/dL) + (4 - albumin \[g/dL\]) \* 0.8
Time frame: Baseline is the average of Day -2 and Day 1 prior to dialysis; End of Study is Day 55
Population: Safety Analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Study in Corrected Calcium (cCa) | -0.08 mmol/L | Standard Deviation 0.1 |
| Etelcalcetide | Change From Baseline to End of Study in Corrected Calcium (cCa) | -0.05 mmol/L | Standard Deviation 0.1 |
Secondary
Change From Baseline to End of Study in Serum Phosphorus
Serum phosphorus was tested at a central laboratory.
Time frame: Baseline is Day 1 prior to dialysis; End of Study is Day 55
Population: Safety Analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Study in Serum Phosphorus | -0.03 mmol/L | Standard Deviation 0.53 |
| Etelcalcetide | Change From Baseline to End of Study in Serum Phosphorus | -0.06 mmol/L | Standard Deviation 0.56 |
Secondary
Change From Baseline to End of Study in Systolic and Diastolic Blood Pressures
Participants remained seated for at least 10 minutes prior to measurement of predialysis heart rate and blood pressure.
Time frame: Baseline Day 1 prior to dialysis; End of Study is Day 55
Population: Safety Analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to End of Study in Systolic and Diastolic Blood Pressures | Systolic Blood Pressure | 1.1 mmHg | Standard Deviation 15.5 |
| Placebo | Change From Baseline to End of Study in Systolic and Diastolic Blood Pressures | Diastolic Blood Pressure | 4.4 mmHg | Standard Deviation 9.2 |
| Etelcalcetide | Change From Baseline to End of Study in Systolic and Diastolic Blood Pressures | Systolic Blood Pressure | 6.1 mmHg | Standard Deviation 18.6 |
| Etelcalcetide | Change From Baseline to End of Study in Systolic and Diastolic Blood Pressures | Diastolic Blood Pressure | 1.5 mmHg | Standard Deviation 11.9 |
Secondary
Change From Baseline to End of Study in Weight
Change from baseline in weight measured at visit.
Time frame: Day 1 up to Day 55
Population: Safety Analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Study in Weight | 1.32 kg | Standard Deviation 0.79 |
| Etelcalcetide | Change From Baseline to End of Study in Weight | 0.76 kg | Standard Deviation 1.39 |
Secondary
Participants With Anti-etelcalcetide Antibody at Baseline and Postbaseline
Participants with positive titers for antibodies to etelcalcetide could be asked to return to the clinical research unit to provide additional serum samples.
Time frame: Baseline: Day 1 prior to dialysis. Postbaseline: Days 29 and 55 prior to dialysis
Population: Safety Analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Etelcalcetide | Participants With Anti-etelcalcetide Antibody at Baseline and Postbaseline | Transient, i.e. negative at last timepoint tested | 0 Participants |
| Etelcalcetide | Participants With Anti-etelcalcetide Antibody at Baseline and Postbaseline | Binding antibody positive at or before baseline | 1 Participants |
| Etelcalcetide | Participants With Anti-etelcalcetide Antibody at Baseline and Postbaseline | Positive postbaseline/negative baseline | 0 Participants |
Secondary
Participants With Clinically-Significant Changes in Electrocardiograms (ECGs) From Baseline to End of Study
Count of participants who exhibited a clinically significant change in the results of their 12-lead electrocardiograms (ECG) when comparing baseline to end of study ECGs.
Time frame: Baseline is Day -2; End of Study is Day 55
Population: Safety Analysis set of participants with both a baseline and end of study ECG.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Participants With Clinically-Significant Changes in Electrocardiograms (ECGs) From Baseline to End of Study | Abnormal Baseline / Normal End of Study | 0 Participants |
| Placebo | Participants With Clinically-Significant Changes in Electrocardiograms (ECGs) From Baseline to End of Study | No Change in Baseline to End of Study | 8 Participants |
| Placebo | Participants With Clinically-Significant Changes in Electrocardiograms (ECGs) From Baseline to End of Study | Normal Baseline / Abnormal End of Study | 0 Participants |
| Etelcalcetide | Participants With Clinically-Significant Changes in Electrocardiograms (ECGs) From Baseline to End of Study | Normal Baseline / Abnormal End of Study | 2 Participants |
| Etelcalcetide | Participants With Clinically-Significant Changes in Electrocardiograms (ECGs) From Baseline to End of Study | Abnormal Baseline / Normal End of Study | 1 Participants |
| Etelcalcetide | Participants With Clinically-Significant Changes in Electrocardiograms (ECGs) From Baseline to End of Study | No Change in Baseline to End of Study | 21 Participants |
Secondary
Participants With Low Corrected Calcium (cCA) By Category
The lowest cCA value for each participant is reported. Total serum calcium was corrected if the serum albumin was \< 4 g/dL or 40 g/L, otherwise cCa equals total serum calcium. The correction formula was: Corrected calcium (mg/dL) = Total calcium (mg/dL) + (4 - albumin \[g/dL\]) \* 0.8
Time frame: Timeframes: Days 8, 15, 22, 27, 29, 34, 41, 55
Population: Safety Analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Participants With Low Corrected Calcium (cCA) By Category | Participants with cCA < 1.75 mmol/L | 0 Participants |
| Placebo | Participants With Low Corrected Calcium (cCA) By Category | Participants with cCA 1.75 to < 1.87 mmol/L | 0 Participants |
| Placebo | Participants With Low Corrected Calcium (cCA) By Category | Participants with cCA 1.87 to < 2.07 mmol/L | 0 Participants |
| Etelcalcetide | Participants With Low Corrected Calcium (cCA) By Category | Participants with cCA < 1.75 mmol/L | 0 Participants |
| Etelcalcetide | Participants With Low Corrected Calcium (cCA) By Category | Participants with cCA 1.75 to < 1.87 mmol/L | 1 Participants |
| Etelcalcetide | Participants With Low Corrected Calcium (cCA) By Category | Participants with cCA 1.87 to < 2.07 mmol/L | 12 Participants |
Secondary
Participants With Treatment-Emergent Adverse Events (TEAEs)
The severity of each adverse event was assessed using the NCI-CTCAE Version 4.0 according to the following: * Grade 1 - Mild: Asymptomatic or mild symptoms; intervention not indicated * Grade 2 - Moderate: Minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL) * Grade 3 - Severe: Medically significant but not life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL * Grade 4 - Life-threatening * Grade 5 - Fatal. A serious AE is an AE that met one or more of the following criteria: * Death * Life-threatening * Required inpatient hospitalization or prolongation of an existing hospitalization * Resulted in persistent or significant disability/incapacity * A congenital anomaly/birth defect * Important medical events that required medical or surgical intervention to prevent one of the outcomes above.
Time frame: Day 1 up to Day 55 (end of study)
Population: Safety Analysis set containing all participants who received at least 1 dose of investigational product (IP)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related Fatal TEAEs | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment discontinuation | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAEs Grade >= 3 | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) | Fatal TEAEs | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) | Trt-related TEAEs leading to study trt discon | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 1 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAEs Grade >= 4 | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related TEAEs Grade >= 3 | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) | All TEAEs | 7 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related TEAEs Grade >= 4 | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAEs | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related serious TEAEs | 0 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAEs | 3 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) | Trt-related TEAEs leading to study trt discon | 0 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related Fatal TEAEs | 0 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) | All TEAEs | 25 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAEs Grade >= 3 | 5 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAEs Grade >= 4 | 1 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related serious TEAEs | 1 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment discontinuation | 0 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) | Fatal TEAEs | 0 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 18 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related TEAEs Grade >= 3 | 1 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related TEAEs Grade >= 4 | 0 Participants |
Secondary
Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest
Terms were coded with Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. Narrow search criteria used for both standardized MedDRA queries (SMQ) and events of interest (EOI). One preferred term (PT) could match multiple EOIs. Infusion Reaction EOI counts included only those events which had onset day coinciding with study medication infusion and resolved on the same day or the day after onset.
Time frame: Day 1 up to Day 55 (end of study)
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Fractures (EOI) | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Hypophosphatemia (EOI) | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Dermatitis (PT) | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Dermatitis allergic (PT) | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Infusion reaction (EOI) | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Rash (PT) | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Hypocalcemia (EOI) | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Hypocalcaemia (PT) | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Blood calcium decreased (PT) | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Adynamic bone (EOI) | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Hypotension (PT) | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Hypersensitivity (SMQ) | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Torsade de pointes-QT prolongation (SMQ) | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Cardiac Failure (EOI) | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Ventricular tachyarrhythmias (SMQ) | 0 Participants |
| Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Convulsions (SMQ) | 0 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Ventricular tachyarrhythmias (SMQ) | 0 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Rash (PT) | 2 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Dermatitis (PT) | 1 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Blood calcium decreased (PT) | 10 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Hypocalcaemia (PT) | 2 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Hypophosphatemia (EOI) | 0 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Convulsions (SMQ) | 0 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Adynamic bone (EOI) | 0 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Fractures (EOI) | 0 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Hypersensitivity (SMQ) | 5 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Dermatitis allergic (PT) | 2 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Hypocalcemia (EOI) | 11 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Infusion reaction (EOI) | 1 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Hypotension (PT) | 1 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Torsade de pointes-QT prolongation (SMQ) | 0 Participants |
| Etelcalcetide | Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest | Cardiac Failure (EOI) | 0 Participants |