Secondary Hyperparathyroidism
Conditions
Keywords
Clinical Trial, Phase 2, Renal Dialysis, Secondary Hyperparathyroidism, Parathyroid hormone
Brief summary
The purpose of this study is to characterize the safety and tolerability and efficacy of multiple ascending doses of etelcalcetide in hemodialysis patients for the treatment of secondary hyperparathyroidism (HPT).
Interventions
DRUGEtelcalcetide
Administered intravenously (IV) at the end of hemodialysis
DRUGPlacebo
Administered intravenously at the end of hemodialysis
Sponsors
KAI Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject provides written informed consent. * Intact parathyroid hormone (PTH) at least 350 pg/mL. * Corrected calcium at least 9.0 mg/dL. * Hemoglobin at least 9.0 g/dL. * Adequate hemodialysis three times per week. * Excepting chronic renal failure, subject is judged to be in stable medical condition based on medical history, physical examination, and routine laboratory tests.
Exclusion criteria
* History or symptomatic ventricular dysrhythmias. * History of angina pectoris or congestive heart failure * History of myocardial infarction, coronary angioplasty, or coronary artery bypass grafting within the past 6 months. * History of or treatment for seizure disorder. * Recent (3 months) parathyroidectomy. * Serum transaminases (alanine aminotransferase, aspartate aminotransferase) greater than two times the upper limit of normal at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Mean Pre-hemodialysis Parathyroid Hormone (PTH) During the Efficacy Assessment Phase | Baseline and the efficacy assessment phase (EAP; defined as the period between 3 days before and 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3) | Baseline is defined as the average of pre-hemodialysis values obtained on day -2 and day 1. The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Mean Parathyroid Hormone ≤ 300 pg/mL During the Efficacy Assessment Phase | Efficacy assessment phase (from 3 days before to 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3) | The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period. |
| Percent Change From Baseline in Mean Corrected Calcium (cCa) During the Efficacy Assessment Phase | Baseline and the efficacy assessment phase (from 3 days before to 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3) | Baseline is defined as the average of pre-hemodialysis values obtained on day -2 and day 1. The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period. |
| Percentage of Participants With ≥ 30% Reduction From Baseline in Mean Parathyroid Hormone During the Efficacy Assessment Phase | Baseline and the efficacy assessment phase (from 3 days before to 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3) | Baseline is defined as the average of pre-hemodialysis values obtained on day -2 and day 1. The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period. |
| Percent Change From Baseline in Corrected Calcium Phosphorus Product (cCa x P) During the Efficacy Assessment Phase | Baseline and the efficacy assessment phase (from 3 days before to 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3) | Baseline is defined as the average of pre-hemodialysis values obtained on day -2 and day 1. The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period. |
| Percentage of Participants With Mean Phosphorus ≤ 4.5 mg/dL or ≤ 5.5 mg/dL During the Efficacy Assessment Phase | Efficacy assessment phase | — |
| Percent Change From Baseline in Mean Phosphorus (P) During the Efficacy Assessment Phase | Baseline and the efficacy assessment phase (from 3 days before to 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3) | Baseline is defined as the average of pre-hemodialysis values obtained on day -2 and day 1. The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 11 study centers in the United States from 17 February 2011 (first participant enrolled) to 24 August 2011 (last participant completed follow up). A total of 87 patients with secondary hyperparathyroidism (HPT) receiving hemodialysis were enrolled and randomized in the study.
Pre-assignment details
This was a multiple-ascending dose study consisting of 3 cohorts: Cohort 1 participants were randomized in a 3:2 ratio to receive etelcalcetide or placebo for 2 weeks; Cohorts 2 and 3 were randomized in a 1:1 ratio to receive etelcalcetide or placebo for 4 weeks. Randomization was stratified by serum parathyroid hormone (\< 600 or ≥ 600 pg/mL).
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Placebo Participants received placebo administered by intravenous injection at the end of each hemodialysis session three times a week (TIW) for 2 weeks. | 4 |
| Cohort 1: Etelcalcetide 5 mg Participants received 5 mg etelcalcetide administered by intravenous injection at the end of each hemodialysis session TIW for 2 weeks. | 6 |
| Cohort 2: Placebo Participants received placebo administered by intravenous injection at the end of each hemodialysis session TIW for 4 weeks. | 21 |
| Cohort 2: Etelcalcetide 10 mg Participants received 10 mg etelcalcetide administered by intravenous injection at the end of each hemodialysis session TIW for 4 weeks. | 21 |
| Cohort 3: Placebo Participants received placebo administered by intravenous injection at the end of each hemodialysis session TIW for 4 weeks. | 13 |
| Cohort 3: Etelcalcetide 5 mg Participants received 5 mg etelcalcetide administered by intravenous injection at the end of each hemodialysis session TIW for 4 weeks. | 13 |
| Total | 78 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Did not Receive Treatment | 1 | 1 | 0 | 0 | 3 | 4 |
| Overall Study | Non-compliance to Study Procedures | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 2: Placebo | Cohort 1: Etelcalcetide 5 mg | Total | Cohort 3: Etelcalcetide 5 mg | Cohort 3: Placebo | Cohort 1: Placebo | Cohort 2: Etelcalcetide 10 mg |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 52.4 years STANDARD_DEVIATION 13.65 | 54.0 years STANDARD_DEVIATION 10 | 53.7 years STANDARD_DEVIATION 12.88 | 59.6 years STANDARD_DEVIATION 10.99 | 56.7 years STANDARD_DEVIATION 11.61 | 47.8 years STANDARD_DEVIATION 16.66 | 50.7 years STANDARD_DEVIATION 13.6 |
| Corrected Calcium | 9.8 mg/dL STANDARD_DEVIATION 0.62 | 9.3 mg/dL STANDARD_DEVIATION 0.44 | 9.6 mg/dL STANDARD_DEVIATION 0.63 | 9.7 mg/dL STANDARD_DEVIATION 0.62 | 9.3 mg/dL STANDARD_DEVIATION 0.58 | 9.1 mg/dL STANDARD_DEVIATION 0.84 | 9.7 mg/dL STANDARD_DEVIATION 0.59 |
| Ethnicity Hispanic or Latino | 0 Participants | 1 Participants | 8 Participants | 3 Participants | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity Not Hispanic or Latino | 21 Participants | 5 Participants | 70 Participants | 10 Participants | 11 Participants | 4 Participants | 19 Participants |
| Parathyroid Hormone | 601.5 pg/mL STANDARD_DEVIATION 239.2 | 588.3 pg/mL STANDARD_DEVIATION 250.52 | 659.4 pg/mL STANDARD_DEVIATION 361.28 | 662.1 pg/mL STANDARD_DEVIATION 442.01 | 619.4 pg/mL STANDARD_DEVIATION 310.35 | 636.3 pg/mL STANDARD_DEVIATION 191.64 | 765.1 pg/mL STANDARD_DEVIATION 480.82 |
| Phosphorus | 6.5 mg/dL STANDARD_DEVIATION 1.83 | — | 5.7 mg/dL STANDARD_DEVIATION 1.49 | 5.0 mg/dL STANDARD_DEVIATION 1.02 | 5.2 mg/dL STANDARD_DEVIATION 1.17 | — | 5.7 mg/dL STANDARD_DEVIATION 1.18 |
| Race Black or African American | 20 Participants | 5 Participants | 63 Participants | 9 Participants | 9 Participants | 2 Participants | 18 Participants |
| Race White | 1 Participants | 1 Participants | 15 Participants | 4 Participants | 4 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Female | 8 Participants | 4 Participants | 30 Participants | 5 Participants | 5 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 13 Participants | 2 Participants | 48 Participants | 8 Participants | 8 Participants | 2 Participants | 15 Participants |
| Stratification Factor: Screening Serum Parathyroid Hormone (PTH) < 600 pg/mL | 11 Participants | 4 Participants | 46 Participants | 9 Participants | 7 Participants | 3 Participants | 12 Participants |
| Stratification Factor: Screening Serum Parathyroid Hormone (PTH) ≥ 600 pg/mL | 10 Participants | 2 Participants | 32 Participants | 4 Participants | 6 Participants | 1 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 4 | 4 / 6 | 5 / 21 | 2 / 21 | 2 / 13 | 3 / 13 |
| serious Total, serious adverse events | 0 / 4 | 1 / 6 | 2 / 21 | 3 / 21 | 1 / 13 | 3 / 13 |
Outcome results
Primary
Percent Change From Baseline in Mean Pre-hemodialysis Parathyroid Hormone (PTH) During the Efficacy Assessment Phase
Baseline is defined as the average of pre-hemodialysis values obtained on day -2 and day 1. The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period.
Time frame: Baseline and the efficacy assessment phase (EAP; defined as the period between 3 days before and 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3)
Population: Modified intent-to-treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Placebo | Percent Change From Baseline in Mean Pre-hemodialysis Parathyroid Hormone (PTH) During the Efficacy Assessment Phase | 0.3 percent change | Standard Deviation 17.11 |
| Cohort 1: Etelcalcetide 5 mg | Percent Change From Baseline in Mean Pre-hemodialysis Parathyroid Hormone (PTH) During the Efficacy Assessment Phase | -19.4 percent change | Standard Deviation 20.65 |
| Cohort 2: Placebo | Percent Change From Baseline in Mean Pre-hemodialysis Parathyroid Hormone (PTH) During the Efficacy Assessment Phase | 28.5 percent change | Standard Deviation 70.39 |
| Cohort 2: Etelcalcetide 10 mg | Percent Change From Baseline in Mean Pre-hemodialysis Parathyroid Hormone (PTH) During the Efficacy Assessment Phase | -49.4 percent change | Standard Deviation 20.42 |
| Cohort 3: Placebo | Percent Change From Baseline in Mean Pre-hemodialysis Parathyroid Hormone (PTH) During the Efficacy Assessment Phase | 2.3 percent change | Standard Deviation 29.44 |
| Cohort 3: Etelcalcetide 5 mg | Percent Change From Baseline in Mean Pre-hemodialysis Parathyroid Hormone (PTH) During the Efficacy Assessment Phase | -33.0 percent change | Standard Deviation 26.28 |
Comparison: The hypothesis for this study (Cohorts 2 and 3) was that intravenous administration of etelcalcetide is superior to placebo for the reduction of PTH after TIW dosing in hemodialysis patients with secondary HPT. This hypothesis was tested in Cohorts 2 and 3 by comparing the mean percent changes from baseline in pre-hemodialysis PTH levels collected during the efficacy phase between the etelcalcetide and placebo groups within each cohort.p-value: <0.000195% CI: [-86.9, -50]ANOVA
Comparison: The hypothesis for this study (Cohorts 2 and 3) was that intravenous administration of etelcalcetide is superior to placebo for the reduction of PTH after TIW dosing in hemodialysis patients with secondary HPT. This hypothesis was tested in Cohorts 2 and 3 by comparing the mean percent changes from baseline in pre-hemodialysis PTH levels collected during the efficacy phase between the etelcalcetide and placebo groups within each cohort.p-value: 0.003295% CI: [-59.8, -13.6]ANOVA
Secondary
Percentage of Participants With ≥ 30% Reduction From Baseline in Mean Parathyroid Hormone During the Efficacy Assessment Phase
Baseline is defined as the average of pre-hemodialysis values obtained on day -2 and day 1. The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period.
Time frame: Baseline and the efficacy assessment phase (from 3 days before to 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3)
Population: Modified intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Placebo | Percentage of Participants With ≥ 30% Reduction From Baseline in Mean Parathyroid Hormone During the Efficacy Assessment Phase | 0.0 percentage of participants |
| Cohort 1: Etelcalcetide 5 mg | Percentage of Participants With ≥ 30% Reduction From Baseline in Mean Parathyroid Hormone During the Efficacy Assessment Phase | 33.3 percentage of participants |
| Cohort 2: Placebo | Percentage of Participants With ≥ 30% Reduction From Baseline in Mean Parathyroid Hormone During the Efficacy Assessment Phase | 9.5 percentage of participants |
| Cohort 2: Etelcalcetide 10 mg | Percentage of Participants With ≥ 30% Reduction From Baseline in Mean Parathyroid Hormone During the Efficacy Assessment Phase | 76.2 percentage of participants |
| Cohort 3: Placebo | Percentage of Participants With ≥ 30% Reduction From Baseline in Mean Parathyroid Hormone During the Efficacy Assessment Phase | 15.4 percentage of participants |
| Cohort 3: Etelcalcetide 5 mg | Percentage of Participants With ≥ 30% Reduction From Baseline in Mean Parathyroid Hormone During the Efficacy Assessment Phase | 53.8 percentage of participants |
p-value: <0.0001Fisher Exact
p-value: 0.0968Fisher Exact
Secondary
Percentage of Participants With Mean Parathyroid Hormone ≤ 300 pg/mL During the Efficacy Assessment Phase
The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period.
Time frame: Efficacy assessment phase (from 3 days before to 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3)
Population: Modified intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Placebo | Percentage of Participants With Mean Parathyroid Hormone ≤ 300 pg/mL During the Efficacy Assessment Phase | 0.0 percentage of participants |
| Cohort 1: Etelcalcetide 5 mg | Percentage of Participants With Mean Parathyroid Hormone ≤ 300 pg/mL During the Efficacy Assessment Phase | 16.7 percentage of participants |
| Cohort 2: Placebo | Percentage of Participants With Mean Parathyroid Hormone ≤ 300 pg/mL During the Efficacy Assessment Phase | 4.8 percentage of participants |
| Cohort 2: Etelcalcetide 10 mg | Percentage of Participants With Mean Parathyroid Hormone ≤ 300 pg/mL During the Efficacy Assessment Phase | 66.7 percentage of participants |
| Cohort 3: Placebo | Percentage of Participants With Mean Parathyroid Hormone ≤ 300 pg/mL During the Efficacy Assessment Phase | 7.7 percentage of participants |
| Cohort 3: Etelcalcetide 5 mg | Percentage of Participants With Mean Parathyroid Hormone ≤ 300 pg/mL During the Efficacy Assessment Phase | 46.2 percentage of participants |
p-value: <0.0001Fisher Exact
p-value: 0.073Fisher Exact
Secondary
Percentage of Participants With Mean Phosphorus ≤ 4.5 mg/dL or ≤ 5.5 mg/dL During the Efficacy Assessment Phase
Time frame: Efficacy assessment phase
Population: Modified intent to treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Placebo | Percentage of Participants With Mean Phosphorus ≤ 4.5 mg/dL or ≤ 5.5 mg/dL During the Efficacy Assessment Phase | Phosphorus ≤ 4.5 mg/dL | 0.0 percentage of participants |
| Cohort 1: Placebo | Percentage of Participants With Mean Phosphorus ≤ 4.5 mg/dL or ≤ 5.5 mg/dL During the Efficacy Assessment Phase | Phosphorus ≤ 5.5 mg/dL | 0.0 percentage of participants |
| Cohort 1: Etelcalcetide 5 mg | Percentage of Participants With Mean Phosphorus ≤ 4.5 mg/dL or ≤ 5.5 mg/dL During the Efficacy Assessment Phase | Phosphorus ≤ 4.5 mg/dL | 0.0 percentage of participants |
| Cohort 1: Etelcalcetide 5 mg | Percentage of Participants With Mean Phosphorus ≤ 4.5 mg/dL or ≤ 5.5 mg/dL During the Efficacy Assessment Phase | Phosphorus ≤ 5.5 mg/dL | 0.0 percentage of participants |
| Cohort 2: Placebo | Percentage of Participants With Mean Phosphorus ≤ 4.5 mg/dL or ≤ 5.5 mg/dL During the Efficacy Assessment Phase | Phosphorus ≤ 4.5 mg/dL | 4.8 percentage of participants |
| Cohort 2: Placebo | Percentage of Participants With Mean Phosphorus ≤ 4.5 mg/dL or ≤ 5.5 mg/dL During the Efficacy Assessment Phase | Phosphorus ≤ 5.5 mg/dL | 33.3 percentage of participants |
| Cohort 2: Etelcalcetide 10 mg | Percentage of Participants With Mean Phosphorus ≤ 4.5 mg/dL or ≤ 5.5 mg/dL During the Efficacy Assessment Phase | Phosphorus ≤ 5.5 mg/dL | 66.7 percentage of participants |
| Cohort 2: Etelcalcetide 10 mg | Percentage of Participants With Mean Phosphorus ≤ 4.5 mg/dL or ≤ 5.5 mg/dL During the Efficacy Assessment Phase | Phosphorus ≤ 4.5 mg/dL | 47.6 percentage of participants |
| Cohort 3: Placebo | Percentage of Participants With Mean Phosphorus ≤ 4.5 mg/dL or ≤ 5.5 mg/dL During the Efficacy Assessment Phase | Phosphorus ≤ 4.5 mg/dL | 15.4 percentage of participants |
| Cohort 3: Placebo | Percentage of Participants With Mean Phosphorus ≤ 4.5 mg/dL or ≤ 5.5 mg/dL During the Efficacy Assessment Phase | Phosphorus ≤ 5.5 mg/dL | 53.8 percentage of participants |
| Cohort 3: Etelcalcetide 5 mg | Percentage of Participants With Mean Phosphorus ≤ 4.5 mg/dL or ≤ 5.5 mg/dL During the Efficacy Assessment Phase | Phosphorus ≤ 5.5 mg/dL | 76.9 percentage of participants |
| Cohort 3: Etelcalcetide 5 mg | Percentage of Participants With Mean Phosphorus ≤ 4.5 mg/dL or ≤ 5.5 mg/dL During the Efficacy Assessment Phase | Phosphorus ≤ 4.5 mg/dL | 46.2 percentage of participants |
Secondary
Percent Change From Baseline in Corrected Calcium Phosphorus Product (cCa x P) During the Efficacy Assessment Phase
Baseline is defined as the average of pre-hemodialysis values obtained on day -2 and day 1. The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period.
Time frame: Baseline and the efficacy assessment phase (from 3 days before to 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3)
Population: Modified intent-to-treat population with available data; Phosphorus data were not collected at baseline for participants in Cohort 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: Placebo | Percent Change From Baseline in Corrected Calcium Phosphorus Product (cCa x P) During the Efficacy Assessment Phase | -0.3 percent change | Standard Deviation 16.25 |
| Cohort 2: Etelcalcetide 10 mg | Percent Change From Baseline in Corrected Calcium Phosphorus Product (cCa x P) During the Efficacy Assessment Phase | -11.0 percent change | Standard Deviation 32.32 |
| Cohort 3: Placebo | Percent Change From Baseline in Corrected Calcium Phosphorus Product (cCa x P) During the Efficacy Assessment Phase | 14.7 percent change | Standard Deviation 35.79 |
| Cohort 3: Etelcalcetide 5 mg | Percent Change From Baseline in Corrected Calcium Phosphorus Product (cCa x P) During the Efficacy Assessment Phase | -12.6 percent change | Standard Deviation 14.99 |
p-value: 0.011295% CI: [-26.8, -4.9]ANOVA
p-value: 0.055495% CI: [-39.3, -1.6]ANOVA
Secondary
Percent Change From Baseline in Mean Corrected Calcium (cCa) During the Efficacy Assessment Phase
Baseline is defined as the average of pre-hemodialysis values obtained on day -2 and day 1. The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period.
Time frame: Baseline and the efficacy assessment phase (from 3 days before to 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3)
Population: Modified intent-to-treat population with available data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Placebo | Percent Change From Baseline in Mean Corrected Calcium (cCa) During the Efficacy Assessment Phase | 1.7 percent change | Standard Deviation 3.76 |
| Cohort 1: Etelcalcetide 5 mg | Percent Change From Baseline in Mean Corrected Calcium (cCa) During the Efficacy Assessment Phase | -7.3 percent change | Standard Deviation 2.62 |
| Cohort 2: Placebo | Percent Change From Baseline in Mean Corrected Calcium (cCa) During the Efficacy Assessment Phase | -1.7 percent change | Standard Deviation 6.25 |
| Cohort 2: Etelcalcetide 10 mg | Percent Change From Baseline in Mean Corrected Calcium (cCa) During the Efficacy Assessment Phase | -13.0 percent change | Standard Deviation 10.17 |
| Cohort 3: Placebo | Percent Change From Baseline in Mean Corrected Calcium (cCa) During the Efficacy Assessment Phase | 1.0 percent change | Standard Deviation 5.26 |
| Cohort 3: Etelcalcetide 5 mg | Percent Change From Baseline in Mean Corrected Calcium (cCa) During the Efficacy Assessment Phase | -6.0 percent change | Standard Deviation 7.95 |
p-value: <0.000195% CI: [-16.4, -8.4]ANOVA
p-value: 0.023595% CI: [-12.8, -1]ANOVA
Secondary
Percent Change From Baseline in Mean Phosphorus (P) During the Efficacy Assessment Phase
Baseline is defined as the average of pre-hemodialysis values obtained on day -2 and day 1. The efficacy assessment phase (defined as 3 days before and 3 days after the last dose of investigational product) value is the mean of all predialysis values obtained during that period.
Time frame: Baseline and the efficacy assessment phase (from 3 days before to 3 days after the last dose of study drug; approximately 2 weeks for Cohort 1 and 4 weeks for Cohorts 2 and 3)
Population: Modified intent-to-treat population with available data; Phosphorus data were not collected at baseline for participants in Cohort 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2: Placebo | Percent Change From Baseline in Mean Phosphorus (P) During the Efficacy Assessment Phase | 1.4 percent change | Standard Deviation 17.92 |
| Cohort 2: Etelcalcetide 10 mg | Percent Change From Baseline in Mean Phosphorus (P) During the Efficacy Assessment Phase | -2.4 percent change | Standard Deviation 26.86 |
| Cohort 3: Placebo | Percent Change From Baseline in Mean Phosphorus (P) During the Efficacy Assessment Phase | 14.1 percent change | Standard Deviation 36.05 |
| Cohort 3: Etelcalcetide 5 mg | Percent Change From Baseline in Mean Phosphorus (P) During the Efficacy Assessment Phase | -7.3 percent change | Standard Deviation 12.83 |
p-value: 0.225595% CI: [-18.6, 5.7]ANOVA
p-value: 0.175195% CI: [-29.8, 5.9]ANOVA