Hemodialysis, Secondary Hyperparathyroidism
Conditions
Keywords
Secondary hyperparathyroidism, Hemodialysis, paricalcitol, maxacalcitol
Brief summary
This study is a exploratory comparison of the efficacy and safety of paricalcitol injection with maxacalcitol injection in chronic kidney disease participants receiving hemodialysis with secondary hyperparathyroidism.
Interventions
DRUGparicalcitol
Intravenous administration 3 times a week immediately before completion of dialysis
DRUGmaxacalcitol
Intravenous administration 3 times a week immediately before completion of dialysis
Sponsors
Abbott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Chronic kidney disease (CKD) patients with iPTH \>=300 pg/mL, adjusted calcium \>=8.4 to \<10.2 mg/dL, and phosphorus \<=6.5 mg/dL * Patients receiving dialysis 3 times weekly for at least 3 months before informed consent was obtained and scheduled to receive the same hemodialysis during the study period * Patients using dialysate with constant concentration of calcium for 4 weeks before informed consent was obtained and receiving phosphate binder with constant dose regimen for 2 weeks before informed consent was obtained
Exclusion criteria
* Patients taking drugs that affect iPTH, calcium, or bone metabolism * Patients with a history of allergic reaction or significant sensitivity to vitamin D * Patients who received parathyroidectomy or ethanol infusion within 1 year before informed consent was obtained * Patients with malignancy or with clinically significant hepatic disease (liver function tests more than 3 times the upper limit of normal) or with refractory hepatic disease * Patients with cardiovascular disease designated as New York Heart Association Class III or IV or with any of the following cardiovascular or cerebrovascular diseases within 6 months before informed consent was obtained: * Acute coronary syndrome (myocardial infarction or unstable angina) or acute cerebral vascular disease (cerebral infarction or cerebral hemorrhage) * Coronary arterial revascularization (such as coronary artery bypass grafting, percutaneous transluminal coronary angioplasty) * Cerebral arterial revascularization (such as cerebral aneurysm clipping, cerebral aneurysm embolization, carotid artery endarterectomy) * Arteriosclerosis obliterans with rest pain (Fontaine classification III or more severe) * Patients with severe hypertension (defined as mean resting blood pressure taken with the patient in a supine position before dialysis and at 6 dialyses sessions before informed consent was obtained: systolic \>= 180 mmHg and diastolic \>= 110 mmHg) * Patients with uncontrolled diabetes mellitus (defined as mean glycosylated hemoglobin \>=8% for 3 months before informed consent was obtained) * Patients with a history of drug or alcohol abuse within 6 months before informed consent was obtained * Patients who require chronic use of cytochrome P450 (CYP3A) inhibitors or inducers * Patients who are taking products that contain aluminum 2 weeks before informed consent was obtained * Patients who have taken paricalcitol in the past
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Percentage of Participants With a >=50% Reduction in Intact Parathyroid Hormone (iPTH) From Baseline Compared to the Average iPTH Obtained in the Last 3 Weeks. | Baseline and the last 3 weeks (Weeks 11, 12, and 13) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean iPTH at Each Visit | Screening (up to 2 weeks before Baseline) to Week 13 | — |
| Mean Change in iPTH From Baseline to the Average iPTH Obtained in the Last 3 Weeks | Baseline and the last 3 weeks (Weeks 11, 12, and 13) | — |
| Percentage of Participants With a >= 50% Reduction in iPTH From Baseline to the Average iPTH Obtained in the Last 3 Weeks and Without Hypercalcemia During Treatment | Baseline and the last 3 weeks (Weeks 11, 12, and 13) for iPTH and anytime during the 12-week treatment period for hypercalcemia | Hypercalcemia was defined as at least 1 corrected calcium \> 11.5 mg/dL or at least 2 consecutive corrected calcium \>= 11.0 mg/dL. |
| The Percentage of Participants With iPTH Within Target Range of 60-180 pg/mL, Based on the Average iPTH Obtained in the Last 3 Weeks | During the last 3 weeks (Weeks 11, 12, and 13) | — |
| Number of Occurrences of iPTH Control, Defined as >=50% Reduction in iPTH From Baseline | Over the 12-week treatment period | — |
| Number of Occurrences of iPTH Control, Defined as Within the Target Range of 60-180 pg/mL of iPTH | Over the 12-week treatment period | — |
| Percentage of Participants With iPTH Within the Target Range of 60-180 pg/mL Based on the Average iPTH Obtained in the Last 3 Weeks of the Study and Without Hypercalcemia Anytime During Treatment | Baseline and the last 3 weeks (Weeks 11, 12, and 13) for iPTH and anytime during the 12-week treatment period for hypercalcemia | Hypercalcemia was defined as at least 1 corrected calcium \> 11.5 mg/dL or at least 2 consecutive corrected calcium \>= 11.0 mg/dL. |
Countries
Japan
Participant flow
Pre-assignment details
Informed consent was obtained from 92 subjects; 45 of these subjects were not enrolled because they did not meet the eligibility criteria at the time of Screening.
Participants by arm
| Arm | Count |
|---|---|
| Paricalcitol 2 mcg with incremental of 1 mcg | 14 |
| Maxacalcitol 5 or 10 mcg with incremental of 2.5 mcg | 33 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
Baseline characteristics
| Characteristic | Maxacalcitol | Paricalcitol | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 14 Participants | 8 Participants | 22 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 6 Participants | 25 Participants |
| Age Continuous | 61.5 years STANDARD_DEVIATION 9.73 | 64.9 years STANDARD_DEVIATION 11.02 | 62.5 years STANDARD_DEVIATION 10.13 |
| Region of Enrollment Japan | 33 participants | 14 participants | 47 participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Male | 28 Participants | 10 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 14 | 31 / 33 |
| serious Total, serious adverse events | 3 / 14 | 3 / 33 |
Outcome results
Primary
The Percentage of Participants With a >=50% Reduction in Intact Parathyroid Hormone (iPTH) From Baseline Compared to the Average iPTH Obtained in the Last 3 Weeks.
Time frame: Baseline and the last 3 weeks (Weeks 11, 12, and 13)
Population: All subjects who received at least 1 dose of study drug and who had at least 1 iPTH measurement while on treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paricalcitol | The Percentage of Participants With a >=50% Reduction in Intact Parathyroid Hormone (iPTH) From Baseline Compared to the Average iPTH Obtained in the Last 3 Weeks. | 50.0 Percentage of participants |
| Maxacalcitol | The Percentage of Participants With a >=50% Reduction in Intact Parathyroid Hormone (iPTH) From Baseline Compared to the Average iPTH Obtained in the Last 3 Weeks. | 36.4 Percentage of participants |
p-value: 0.51895% CI: [-22.36, 49.63]Fisher Exact
Secondary
Mean Change in iPTH From Baseline to the Average iPTH Obtained in the Last 3 Weeks
Time frame: Baseline and the last 3 weeks (Weeks 11, 12, and 13)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paricalcitol | Mean Change in iPTH From Baseline to the Average iPTH Obtained in the Last 3 Weeks | -208.4 pg/mL | Standard Deviation 136.7 |
| Maxacalcitol | Mean Change in iPTH From Baseline to the Average iPTH Obtained in the Last 3 Weeks | -240.4 pg/mL | Standard Deviation 152.73 |
Secondary
Mean iPTH at Each Visit
Time frame: Screening (up to 2 weeks before Baseline) to Week 13
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paricalcitol | Mean iPTH at Each Visit | Screening (up to 2 weeks before Baseline) | 462.7 pg/mL | Standard Deviation 127.62 |
| Paricalcitol | Mean iPTH at Each Visit | Baseline (Week 1) | 507.6 pg/mL | Standard Deviation 162.47 |
| Paricalcitol | Mean iPTH at Each Visit | Week 2 | 479.2 pg/mL | Standard Deviation 178.43 |
| Paricalcitol | Mean iPTH at Each Visit | Week 3 | 474.4 pg/mL | Standard Deviation 201.98 |
| Paricalcitol | Mean iPTH at Each Visit | Week 4 | 401.3 pg/mL | Standard Deviation 209.24 |
| Paricalcitol | Mean iPTH at Each Visit | Week 5 | 373.2 pg/mL | Standard Deviation 181.64 |
| Paricalcitol | Mean iPTH at Each Visit | Week 6 | 304.8 pg/mL | Standard Deviation 136.76 |
| Paricalcitol | Mean iPTH at Each Visit | Week 7 | 282.2 pg/mL | Standard Deviation 152.76 |
| Paricalcitol | Mean iPTH at Each Visit | Week 8 | 256.9 pg/mL | Standard Deviation 142.39 |
| Paricalcitol | Mean iPTH at Each Visit | Week 9 | 275.9 pg/mL | Standard Deviation 158.39 |
| Paricalcitol | Mean iPTH at Each Visit | Week 10 | 312.6 pg/mL | Standard Deviation 140.45 |
| Paricalcitol | Mean iPTH at Each Visit | Week 11 | 279.6 pg/mL | Standard Deviation 159.69 |
| Paricalcitol | Mean iPTH at Each Visit | Week 12 | 291.5 pg/mL | Standard Deviation 163.51 |
| Paricalcitol | Mean iPTH at Each Visit | Week 13 | 293.0 pg/mL | Standard Deviation 164.74 |
| Maxacalcitol | Mean iPTH at Each Visit | Week 10 | 361.2 pg/mL | Standard Deviation 228.37 |
| Maxacalcitol | Mean iPTH at Each Visit | Screening (up to 2 weeks before Baseline) | 536.4 pg/mL | Standard Deviation 190.72 |
| Maxacalcitol | Mean iPTH at Each Visit | Week 7 | 292.8 pg/mL | Standard Deviation 187.02 |
| Maxacalcitol | Mean iPTH at Each Visit | Baseline (Week 1) | 595.9 pg/mL | Standard Deviation 213.8 |
| Maxacalcitol | Mean iPTH at Each Visit | Week 12 | 341.6 pg/mL | Standard Deviation 192.65 |
| Maxacalcitol | Mean iPTH at Each Visit | Week 2 | 474.8 pg/mL | Standard Deviation 201 |
| Maxacalcitol | Mean iPTH at Each Visit | Week 8 | 315.1 pg/mL | Standard Deviation 229.53 |
| Maxacalcitol | Mean iPTH at Each Visit | Week 3 | 381.8 pg/mL | Standard Deviation 181.07 |
| Maxacalcitol | Mean iPTH at Each Visit | Week 11 | 345.1 pg/mL | Standard Deviation 189.52 |
| Maxacalcitol | Mean iPTH at Each Visit | Week 4 | 310.2 pg/mL | Standard Deviation 158.68 |
| Maxacalcitol | Mean iPTH at Each Visit | Week 9 | 358.8 pg/mL | Standard Deviation 252.98 |
| Maxacalcitol | Mean iPTH at Each Visit | Week 5 | 279.7 pg/mL | Standard Deviation 155.07 |
| Maxacalcitol | Mean iPTH at Each Visit | Week 13 | 326.4 pg/mL | Standard Deviation 180.33 |
| Maxacalcitol | Mean iPTH at Each Visit | Week 6 | 262.3 pg/mL | Standard Deviation 144.72 |
Secondary
Number of Occurrences of iPTH Control, Defined as >=50% Reduction in iPTH From Baseline
Time frame: Over the 12-week treatment period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paricalcitol | Number of Occurrences of iPTH Control, Defined as >=50% Reduction in iPTH From Baseline | 3.4 Occurrences per participant | Standard Deviation 2.98 |
| Maxacalcitol | Number of Occurrences of iPTH Control, Defined as >=50% Reduction in iPTH From Baseline | 4.8 Occurrences per participant | Standard Deviation 2.96 |
Secondary
Number of Occurrences of iPTH Control, Defined as Within the Target Range of 60-180 pg/mL of iPTH
Time frame: Over the 12-week treatment period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paricalcitol | Number of Occurrences of iPTH Control, Defined as Within the Target Range of 60-180 pg/mL of iPTH | 2.3 Occurrences per participant | Standard Deviation 2.7 |
| Maxacalcitol | Number of Occurrences of iPTH Control, Defined as Within the Target Range of 60-180 pg/mL of iPTH | 2.7 Occurrences per participant | Standard Deviation 2.67 |
Secondary
Percentage of Participants With a >= 50% Reduction in iPTH From Baseline to the Average iPTH Obtained in the Last 3 Weeks and Without Hypercalcemia During Treatment
Hypercalcemia was defined as at least 1 corrected calcium \> 11.5 mg/dL or at least 2 consecutive corrected calcium \>= 11.0 mg/dL.
Time frame: Baseline and the last 3 weeks (Weeks 11, 12, and 13) for iPTH and anytime during the 12-week treatment period for hypercalcemia
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paricalcitol | Percentage of Participants With a >= 50% Reduction in iPTH From Baseline to the Average iPTH Obtained in the Last 3 Weeks and Without Hypercalcemia During Treatment | 50.0 Percentage of participants |
| Maxacalcitol | Percentage of Participants With a >= 50% Reduction in iPTH From Baseline to the Average iPTH Obtained in the Last 3 Weeks and Without Hypercalcemia During Treatment | 33.3 Percentage of participants |
Secondary
Percentage of Participants With iPTH Within the Target Range of 60-180 pg/mL Based on the Average iPTH Obtained in the Last 3 Weeks of the Study and Without Hypercalcemia Anytime During Treatment
Hypercalcemia was defined as at least 1 corrected calcium \> 11.5 mg/dL or at least 2 consecutive corrected calcium \>= 11.0 mg/dL.
Time frame: Baseline and the last 3 weeks (Weeks 11, 12, and 13) for iPTH and anytime during the 12-week treatment period for hypercalcemia
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paricalcitol | Percentage of Participants With iPTH Within the Target Range of 60-180 pg/mL Based on the Average iPTH Obtained in the Last 3 Weeks of the Study and Without Hypercalcemia Anytime During Treatment | 28.6 Percentage of participants |
| Maxacalcitol | Percentage of Participants With iPTH Within the Target Range of 60-180 pg/mL Based on the Average iPTH Obtained in the Last 3 Weeks of the Study and Without Hypercalcemia Anytime During Treatment | 12.1 Percentage of participants |
Secondary
The Percentage of Participants With iPTH Within Target Range of 60-180 pg/mL, Based on the Average iPTH Obtained in the Last 3 Weeks
Time frame: During the last 3 weeks (Weeks 11, 12, and 13)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paricalcitol | The Percentage of Participants With iPTH Within Target Range of 60-180 pg/mL, Based on the Average iPTH Obtained in the Last 3 Weeks | 28.6 Percentage of participants |
| Maxacalcitol | The Percentage of Participants With iPTH Within Target Range of 60-180 pg/mL, Based on the Average iPTH Obtained in the Last 3 Weeks | 15.2 Percentage of participants |