Secondary Hyperparathyroidism
Conditions
Keywords
Clinical Trial, Phase 2, Renal Dialysis, Secondary Hyperparathyroidism, Chronic kidney disease-mineral and bone disorder, Parathyroid hormone
Brief summary
The purpose of this study is to evaluate the effect of thrice weekly intravenous (IV) administration of etelcalcetide in the treatment of secondary hyperparathyroidism (SHPT) in hemodialysis patients with chronic kidney disease-mineral and bone disorder (CKD-MBD).
Interventions
DRUGEtelcalcetide
Administered 3 times a week by bolus injection into the venous line of the dialysis circuit after the end of hemodialysis.
Sponsors
KAI Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects provides written informed consent * Screening intact PTH (iPTH) ≥ 350 pg/mL and corrected calcium ≥ 8.5 mg/dL * Hemoglobin ≥ 8.5 g/dL * Serum transaminases (alanine transaminase \[ALT\], aspartate transaminase \[AST\]) less than 2.5 times the upper limit of normal * Adequate hemodialysis three times per week
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 within the last 12 months * Postdialysis systolic blood pressure \> 180 mmHg or diastolic blood pressure \> 90 mmHg * Serum magnesium below the lower limit of normal at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Parathyroid Hormone (PTH) During the Efficacy Period | Baseline and the efficacy period, defined as from 14 days prior to and 3 days after the last dose of study drug (approximately days 68 - 85 for participants who completed 12 weeks of treatment) | Baseline was defined as the average of 3 predialysis PTH results obtained within 3 weeks of and prior to the first dose of study drug. The efficacy period (defined as the period from 14 days prior to and 3 days after the last dose of study drug) value was the mean of the prehemodialysis values obtained during that period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With ≥ 30% Reduction in PTH From Baseline During the Efficacy Period | Baseline and the efficacy period, defined as from 14 days prior to and 3 days after the last dose of study drug (approximately days 68 - 85 for participants who completed 12 weeks of treatment) | The efficacy period (defined as the period from 14 days prior to and 3 days after the last dose of study drug) value was the mean of the prehemodialysis values obtained during that period. |
| Percentage of Participants With PTH ≤ 300 pg/mL During the Efficacy Period | The efficacy period, defined as from 14 days prior to and 3 days after the last dose of study drug (approximately days 68 - 85 for participants who completed 12 weeks of treatment) | The efficacy period (defined as the period from 14 days prior to and 3 days after the last dose of study drug) value was the mean of the prehemodialysis values obtained during that period. |
| Percent Change From Baseline in Corrected Calcium During the Efficacy Period | Baseline and the efficacy period, defined as from 14 days prior to and 3 days after the last dose of study drug (approximately days 68 - 85 for participants who completed 12 weeks of treatment) | Baseline was defined as the average of 3 predialysis PTH results obtained within 3 weeks of and prior to the first dose of study drug. The efficacy period (defined as the period from 14 days prior to and 3 days after the last dose of study drug) value was the mean of the prehemodialysis values obtained during that period. |
| Percent Change From Baseline in Phosphorus During the Efficacy Period | Baseline and the efficacy period, defined as from 14 days prior to and 3 days after the last dose of study drug (approximately days 68 - 85 for participants who completed 12 weeks of treatment) | Baseline was defined as the average of 3 predialysis PTH results obtained within 3 weeks of and prior to the first dose of study drug. The efficacy period (defined as the period from 14 days prior to and 3 days after the last dose of study drug) value was the mean of the prehemodialysis values obtained during that period. |
Participant flow
Recruitment details
This study was conducted at 5 centers in the United States from 05 December 2011 (first participant enrolled) to 21 May 2012 (last participant completed follow-up).
Participants by arm
| Arm | Count |
|---|---|
| Etelcalcetide Participants received etelcalcetide three times a week (TIW) administered by intravenous bolus injection at the end of each hemodialysis session for 12 weeks. The starting dose was 5 mg and may have been titrated every 4 weeks based on the preceding serum parathyroid hormone (PTH) and corrected calcium (cCa) levels to a maximum dose of 20 mg per hemodialysis session in order to achieve the targeted PTH range while maintaining serum calcium within an acceptable range. | 37 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Other | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Etelcalcetide |
|---|---|
| Age, Continuous | 56.5 years STANDARD_DEVIATION 13.3 |
| Corrected Calcium | 10.1 mg/dL STANDARD_DEVIATION 0.62 |
| Ethnicity Hispanic or Latino | 11 Participants |
| Ethnicity Not Hispanic or Latino | 26 Participants |
| Parathyroid Hormone Category ≤ 700 pg/mL | 22 Participants |
| Parathyroid Hormone Category > 700 pg/mL | 15 Participants |
| Parathyroid Hormone (PTH) | 853.4 pg/mL STANDARD_DEVIATION 644.25 |
| Phosphorus | 5.7 mg/dL STANDARD_DEVIATION 1.38 |
| Race Black or African American | 19 Participants |
| Race White | 18 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 18 / 37 |
| serious Total, serious adverse events | 3 / 37 |
Outcome results
Primary
Percent Change From Baseline in Parathyroid Hormone (PTH) During the Efficacy Period
Baseline was defined as the average of 3 predialysis PTH results obtained within 3 weeks of and prior to the first dose of study drug. The efficacy period (defined as the period from 14 days prior to and 3 days after the last dose of study drug) value was the mean of the prehemodialysis values obtained during that period.
Time frame: Baseline and the efficacy period, defined as from 14 days prior to and 3 days after the last dose of study drug (approximately days 68 - 85 for participants who completed 12 weeks of treatment)
Population: The modified intent-to-treat population (all participants who were randomized and received treatment) with available data at both time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etelcalcetide | Percent Change From Baseline in Parathyroid Hormone (PTH) During the Efficacy Period | -53.6 percent change | Standard Deviation 21.42 |
| Baseline PTH ≤ 700 pg/mL | Percent Change From Baseline in Parathyroid Hormone (PTH) During the Efficacy Period | -55.6 percent change | Standard Deviation 19.65 |
| Baseline PTH > 700 pg/mL | Percent Change From Baseline in Parathyroid Hormone (PTH) During the Efficacy Period | -50.8 percent change | Standard Deviation 24.12 |
Secondary
Percentage of Participants With ≥ 30% Reduction in PTH From Baseline During the Efficacy Period
The efficacy period (defined as the period from 14 days prior to and 3 days after the last dose of study drug) value was the mean of the prehemodialysis values obtained during that period.
Time frame: Baseline and the efficacy period, defined as from 14 days prior to and 3 days after the last dose of study drug (approximately days 68 - 85 for participants who completed 12 weeks of treatment)
Population: Modified intent-to-treat population with available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etelcalcetide | Percentage of Participants With ≥ 30% Reduction in PTH From Baseline During the Efficacy Period | 89 percentage of participants |
| Baseline PTH ≤ 700 pg/mL | Percentage of Participants With ≥ 30% Reduction in PTH From Baseline During the Efficacy Period | 95 percentage of participants |
| Baseline PTH > 700 pg/mL | Percentage of Participants With ≥ 30% Reduction in PTH From Baseline During the Efficacy Period | 80 percentage of participants |
Secondary
Percentage of Participants With PTH ≤ 300 pg/mL During the Efficacy Period
The efficacy period (defined as the period from 14 days prior to and 3 days after the last dose of study drug) value was the mean of the prehemodialysis values obtained during that period.
Time frame: The efficacy period, defined as from 14 days prior to and 3 days after the last dose of study drug (approximately days 68 - 85 for participants who completed 12 weeks of treatment)
Population: Modified intent-to-treat population with available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etelcalcetide | Percentage of Participants With PTH ≤ 300 pg/mL During the Efficacy Period | 56 percentage of participants |
| Baseline PTH ≤ 700 pg/mL | Percentage of Participants With PTH ≤ 300 pg/mL During the Efficacy Period | 76 percentage of participants |
| Baseline PTH > 700 pg/mL | Percentage of Participants With PTH ≤ 300 pg/mL During the Efficacy Period | 27 percentage of participants |
Secondary
Percent Change From Baseline in Corrected Calcium During the Efficacy Period
Baseline was defined as the average of 3 predialysis PTH results obtained within 3 weeks of and prior to the first dose of study drug. The efficacy period (defined as the period from 14 days prior to and 3 days after the last dose of study drug) value was the mean of the prehemodialysis values obtained during that period.
Time frame: Baseline and the efficacy period, defined as from 14 days prior to and 3 days after the last dose of study drug (approximately days 68 - 85 for participants who completed 12 weeks of treatment)
Population: Modified intent-to-treat population with available data at both time points
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etelcalcetide | Percent Change From Baseline in Corrected Calcium During the Efficacy Period | -15.1 percent change | Standard Deviation 5.76 |
| Baseline PTH ≤ 700 pg/mL | Percent Change From Baseline in Corrected Calcium During the Efficacy Period | -13.0 percent change | Standard Deviation 4.83 |
| Baseline PTH > 700 pg/mL | Percent Change From Baseline in Corrected Calcium During the Efficacy Period | -17.9 percent change | Standard Deviation 5.91 |
Secondary
Percent Change From Baseline in Phosphorus During the Efficacy Period
Baseline was defined as the average of 3 predialysis PTH results obtained within 3 weeks of and prior to the first dose of study drug. The efficacy period (defined as the period from 14 days prior to and 3 days after the last dose of study drug) value was the mean of the prehemodialysis values obtained during that period.
Time frame: Baseline and the efficacy period, defined as from 14 days prior to and 3 days after the last dose of study drug (approximately days 68 - 85 for participants who completed 12 weeks of treatment)
Population: Modified intent-to-treat population with available data at both time points
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etelcalcetide | Percent Change From Baseline in Phosphorus During the Efficacy Period | -10.4 percent change | Standard Deviation 19.78 |
| Baseline PTH ≤ 700 pg/mL | Percent Change From Baseline in Phosphorus During the Efficacy Period | -7.7 percent change | Standard Deviation 21.92 |
| Baseline PTH > 700 pg/mL | Percent Change From Baseline in Phosphorus During the Efficacy Period | -14.2 percent change | Standard Deviation 16.27 |