Hemodialysis, Secondary Hyperparathyroidism
Conditions
Keywords
Secondary hyperparathyroidism, Paricalcitol, Hemodialysis, Maxacalcitol
Brief summary
This study is a comparison of the efficacy and safety of paricalcitol injection with maxacalcitol injection in adult Japanese chronic kidney disease patients receiving hemodialysis with secondary hyperparathyroidism. The main objective of this study is to demonstrate the efficacy of paricalcitol injection in reducing levels of parathyroid hormone without clinically significant hypercalcemia, compared to maxacalcitol injection.
Interventions
Sponsors
AbbVie (prior sponsor, Abbott)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult Chronic Kidney Disease (CKD) Stage 5 patients undergoing dialysis with stable dialysate calcium and phosphate binders * On three times weekly hemodialysis for at least 3 months prior with intact parathyroid hormone (iPTH) greater than or equal to 300 pg/mL, adjusted normalized serum total calcium (Ca) greater than or equal to 8.4 to less than 10.2 mg/dL, serum phosphorus (P) less than or equal to 6.5 mg/dL.
Exclusion criteria
* Patients with a recent history of severe cardiovascular or hepatic disease, uncontrolled hypertension or uncontrolled diabetes * Patients who have received a parathyroidectomy or ethanol infusion within the prior year * Patients taking drugs that affect iPTH, calcium or bone metabolism * Patients who will need to take chronic doses (greater than or equal to 2 consecutive weeks) of cytochrome P450 inhibitors (e.g., clarithromycin, grapefruit products) or inducers (e.g., carbamazepine, rifampicin) * Female patients who are pregnant, possibly pregnant, wish to become pregnant, or participate in breastfeeding during the study period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Target Intact Parathyroid Hormone (iPTH) and Without Hypercalcemia | iPTH measured during the last three weeks of treatment (Weeks 11, 12, and 13). Calcium measured throughout the study (Weeks 1-13). | The target iPTH range was 60-180 pg/mL, based on the average of the last 3 weeks of treatment, and with no hypercalcemia during the treatment phase. Hypercalcemia was defined as at least 1 corrected calcium value \> 11.0 mg/dL or at least 2 corrected calcium values ≥ 10.5 mg/dL. iPTH was measured before the first dialysis session of each week and analyzed by the central laboratory. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With ≥ 50% Reduction in Intact Parathyroid Hormone (iPTH) From Baseline | Baseline to the last three weeks of treatment (Weeks 11, 12, and 13) | The percentage of participants with a greater than or equal to 50% reduction in intact parathyroid hormone (iPTH) from baseline to the average of the last 3 weeks of treatment. iPTH was measured before the first dialysis session of each week and analyzed by the central laboratory. |
| Percentage of Participants With ≥ 50% Reduction in Intact Parathyroid Hormone (iPTH) From Baseline and With No Hypercalcemia | Baseline to the last three weeks of treatment (Weeks 11, 12, and 13) for iPTH. Calcium measured throughout the study (Weeks 1-13). | The percentage of participants with greater than or equal to 50% reduction in intact parathyroid hormone (iPTH) from baseline to the average of the last 3 weeks of treatment and with no hypercalcemia during the treatment phase. iPTH was measured before the first dialysis session of each week and analyzed by the central laboratory. Hypercalcemia was defined as at least 1 corrected calcium value \> 11.0 mg/dL or at least 2 corrected calcium values ≥ 10.5 mg/dL. |
| Percentage of Participants With Target Intact Parathyroid Hormone (iPTH) | The last three weeks of treatment (Weeks 11, 12, and 13) | The target iPTH range was 60-180 pg/mL, based on the average of the last 3 weeks of treatment. iPTH was measured before the first dialysis session of each week and analyzed by the central laboratory. |
| Number of Visits at Which Participants Achieved iPTH Control With ≥ 50% Reduction in Intact Parathyroid Hormone (iPTH) From Baseline | Weeks 2 to 13 | iPTH control was defined as a ≥ 50% reduction from baseline. iPTH was measured before the first dialysis session of the week, each week during the treatment phase and analyzed by the central laboratory. |
| Number of Visits at Which Participants Achieved iPTH Control in the Target Range of 60 to 180 pg/mL | Weeks 2 to 13 | iPTH control was defined as being within the target range of 60 to 180 pg/mL. iPTH was measured before the first dialysis session of the week, once a week during the treatment phase and analyzed by the central laboratory. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Paricalcitol Participants received paricalcitol at an initial dose of 2 µg, and maxacalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 1 µg based on protocol-specified criteria up to a maximum of 7 µg. | 127 |
| Maxacalcitol Participants received maxacalcitol at an initial dose of 5 µg (iPTH \< 500 pg/mL at Screening) or 10 µg (iPTH ≥ 500 pg/mL at Screening), and paricalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 2.5 µg based on protocol-specified criteria up to a maximum of 20 µg. | 128 |
| Total | 255 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | 2 consecutive calcium values >11.5 mg/dL | 0 | 1 |
| Overall Study | 2 consecutive calcium values < 8.4 mg/dL | 3 | 3 |
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Missed 3 consecutive doses | 0 | 4 |
| Overall Study | Other | 5 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 5 |
Baseline characteristics
| Characteristic | Maxacalcitol | Total | Paricalcitol |
|---|---|---|---|
| Age Continuous | 61.6 years STANDARD_DEVIATION 12.46 | 61.6 years STANDARD_DEVIATION 11.85 | 61.5 years STANDARD_DEVIATION 11.24 |
| Duration of hemodialysis | 8.9 years STANDARD_DEVIATION 7.5 | 8.6 years STANDARD_DEVIATION 7.12 | 8.4 years STANDARD_DEVIATION 6.73 |
| Intact parathyroid hormone level | 527.1 pg/mL STANDARD_DEVIATION 203.33 | 526.3 pg/mL STANDARD_DEVIATION 204.03 | 525.4 pg/mL STANDARD_DEVIATION 205.55 |
| Race/Ethnicity, Customized Asian | 128 participants | 255 participants | 127 participants |
| Race/Ethnicity, Customized Other | 0 participants | 0 participants | 0 participants |
| Region of Enrollment Japan | 128 participants | 255 participants | 127 participants |
| Sex: Female, Male Female | 47 Participants | 92 Participants | 45 Participants |
| Sex: Female, Male Male | 81 Participants | 163 Participants | 82 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 118 / 127 | 123 / 128 |
| serious Total, serious adverse events | 10 / 127 | 15 / 128 |
Outcome results
Primary
Percentage of Participants With Target Intact Parathyroid Hormone (iPTH) and Without Hypercalcemia
The target iPTH range was 60-180 pg/mL, based on the average of the last 3 weeks of treatment, and with no hypercalcemia during the treatment phase. Hypercalcemia was defined as at least 1 corrected calcium value \> 11.0 mg/dL or at least 2 corrected calcium values ≥ 10.5 mg/dL. iPTH was measured before the first dialysis session of each week and analyzed by the central laboratory.
Time frame: iPTH measured during the last three weeks of treatment (Weeks 11, 12, and 13). Calcium measured throughout the study (Weeks 1-13).
Population: The per-protocol set (PPS) consists of all randomized patients who completed at least 8 weeks of treatment and met the conditions specified by the subject classification (i.e., no violation of inclusion/exclusion criteria) that occurred before the study blind was broken.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paricalcitol | Percentage of Participants With Target Intact Parathyroid Hormone (iPTH) and Without Hypercalcemia | 27.7 percentage of participants |
| Maxacalcitol | Percentage of Participants With Target Intact Parathyroid Hormone (iPTH) and Without Hypercalcemia | 30.5 percentage of participants |
Secondary
Number of Visits at Which Participants Achieved iPTH Control in the Target Range of 60 to 180 pg/mL
iPTH control was defined as being within the target range of 60 to 180 pg/mL. iPTH was measured before the first dialysis session of the week, once a week during the treatment phase and analyzed by the central laboratory.
Time frame: Weeks 2 to 13
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paricalcitol | Number of Visits at Which Participants Achieved iPTH Control in the Target Range of 60 to 180 pg/mL | 2.6 visits | Standard Deviation 2.51 |
| Maxacalcitol | Number of Visits at Which Participants Achieved iPTH Control in the Target Range of 60 to 180 pg/mL | 3.4 visits | Standard Deviation 2.84 |
Secondary
Number of Visits at Which Participants Achieved iPTH Control With ≥ 50% Reduction in Intact Parathyroid Hormone (iPTH) From Baseline
iPTH control was defined as a ≥ 50% reduction from baseline. iPTH was measured before the first dialysis session of the week, each week during the treatment phase and analyzed by the central laboratory.
Time frame: Weeks 2 to 13
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paricalcitol | Number of Visits at Which Participants Achieved iPTH Control With ≥ 50% Reduction in Intact Parathyroid Hormone (iPTH) From Baseline | 3.9 visits | Standard Deviation 2.97 |
| Maxacalcitol | Number of Visits at Which Participants Achieved iPTH Control With ≥ 50% Reduction in Intact Parathyroid Hormone (iPTH) From Baseline | 5.3 visits | Standard Deviation 3.17 |
Secondary
Percentage of Participants With ≥ 50% Reduction in Intact Parathyroid Hormone (iPTH) From Baseline
The percentage of participants with a greater than or equal to 50% reduction in intact parathyroid hormone (iPTH) from baseline to the average of the last 3 weeks of treatment. iPTH was measured before the first dialysis session of each week and analyzed by the central laboratory.
Time frame: Baseline to the last three weeks of treatment (Weeks 11, 12, and 13)
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paricalcitol | Percentage of Participants With ≥ 50% Reduction in Intact Parathyroid Hormone (iPTH) From Baseline | 44.9 percentage of participants |
| Maxacalcitol | Percentage of Participants With ≥ 50% Reduction in Intact Parathyroid Hormone (iPTH) From Baseline | 50.8 percentage of participants |
Secondary
Percentage of Participants With ≥ 50% Reduction in Intact Parathyroid Hormone (iPTH) From Baseline and With No Hypercalcemia
The percentage of participants with greater than or equal to 50% reduction in intact parathyroid hormone (iPTH) from baseline to the average of the last 3 weeks of treatment and with no hypercalcemia during the treatment phase. iPTH was measured before the first dialysis session of each week and analyzed by the central laboratory. Hypercalcemia was defined as at least 1 corrected calcium value \> 11.0 mg/dL or at least 2 corrected calcium values ≥ 10.5 mg/dL.
Time frame: Baseline to the last three weeks of treatment (Weeks 11, 12, and 13) for iPTH. Calcium measured throughout the study (Weeks 1-13).
Population: The Full Analysis Set (FAS) consists of all randomized patients who received at least 1 dose of study drug and had at least 1 post-baseline iPTH measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paricalcitol | Percentage of Participants With ≥ 50% Reduction in Intact Parathyroid Hormone (iPTH) From Baseline and With No Hypercalcemia | 34.6 percentage of participants |
| Maxacalcitol | Percentage of Participants With ≥ 50% Reduction in Intact Parathyroid Hormone (iPTH) From Baseline and With No Hypercalcemia | 39.1 percentage of participants |
Secondary
Percentage of Participants With Target Intact Parathyroid Hormone (iPTH)
The target iPTH range was 60-180 pg/mL, based on the average of the last 3 weeks of treatment. iPTH was measured before the first dialysis session of each week and analyzed by the central laboratory.
Time frame: The last three weeks of treatment (Weeks 11, 12, and 13)
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paricalcitol | Percentage of Participants With Target Intact Parathyroid Hormone (iPTH) | 31.5 percentage of participants |
| Maxacalcitol | Percentage of Participants With Target Intact Parathyroid Hormone (iPTH) | 32.8 percentage of participants |