Chronic Kidney Disease, Secondary Hyperparathyroidism, Vitamin D Insufficiency
Conditions
Keywords
Parathyroid Diseases, Renal Insufficiency, Kidney Failure, Chronic, Hyperparathyroidism, Secondary, Vitamin D, Hyperparathyroidism, Kidney Diseases, Kidney Failure, Renal Insufficiency, Chronic
Brief summary
This study will investigate how the levels of a repeat dose of CTAP101 changes in the body over time (pharmacokinetics, PK) and how CTAP101 affects other mineral and hormonal balances (pharmacodynamics, PD) in patients with chronic kidney disease (CKD, vitamin D insufficiency and secondary hyperparathyroidism (SHPT).
Interventions
DRUGCohort 1 CTAP101 Capsules- 60µg
60µg of CTAP101 capsules given once daily for 42 days.
DRUGCohort 1 CTAP101 Capsules - 90µg
90µg of CTAP101 capsules given once daily for 42 days.
DRUGCohort 1 Matching Sugar Capsule
Placebo capsules given once daily for 42 days.
DRUGCohort 2 CTAP101 Capsules - 30µg
30µg of CTAP101 capsules given once daily for 42 days.
DRUGCohort 2 Matching Sugar Capsule
Placebo capsules given once daily for 42 days.
Sponsors
OPKO Health, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Urinary albumin excretion of ≤3000 μg of creatinine 2. Stage 3 CKD 3. Plasma iPTH: \> 70 pg/mL and \< 500 pg/mL 4. Serum Ca: ≥ 8.4 mg/dL and \< 10.0 mg/dL 5. Serum P: ≥ 2.0 mg/dL and \< 5.0 mg/dL 6. Serum 25-hydroxyvitamin D: \> 10 ng/mL and \< 29 ng/mL. 7. Discontinue vitamin D use for duration of study
Exclusion criteria
1. History of kidney transplant or parathyroidectomy 2. Spot urine calcium:creatinine ratio \> 0.2 3. Current serious illness, such as malignancy, HIV, liver disease, cardiovascular event or hepatitis 4. Currently on dialysis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion (%) of Subjects With Serum 25-hydroxyvitamin D ≥30 ng/mL (PP). | 6 weeks | The proportion of subjects in the per protocol population with serum 25-hydroxyvitamin D ≥30 ng/mL at End-of-Treatment (EOT; Week 6) in Cohorts 1 and 2 (60/90 and 30 μg groups, respectively) were compared to their corresponding placebo groups. |
| Mean Percent Change From Baseline in Plasma Intact Parathyroid Hormone (iPTH) to End of Treatment (Per Protocol Population) | 6 weeks | Mean percent change from baseline in plasma intact parathyroid hormone (iPTH) from baseline to End of Treatment (EOT) in the Per Protocol population. Subjects in Cohorts 1 and 2 (dose regimens 60/90 and 30 mcg, respectively) were compared to their respective placebo groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Serum 25-hydroxyvitamin D at Week 6 | Baseline to End of Treatment (6 weeks) | Mean absolute change from baseline in serum total 25-hydroxyvitamin D to end of treatment (EOT) |
| Percent Change From Baseline in Serum 25-hydroxyvitamin D at End of Treatment (EOT, Week 6) in the Per Protocol Population | Baseline to End of Treatment (6 weeks) | Mean percent change from baseline in serum 25-hydroxyvitamin D at End of Treatment (EOT, week 6) in the per protocol population. Subjects in Cohorts 1 and 2 (dose regimens of 60/90 and 30 mcg, respectively) were compared versus their corresponding placebo groups. |
| Proportion of Subjects With Reduction of Intact Parathyroid Hormone (iPTH) of at Least 30% at Week 6 | Baseline to End of Treatment (6 weeks) | Proportion of subjects with at least 30% reduction in plasma intact parathyroid hormone (iPTH) and/or mean iPTH reduction to 70 pg/mL or less at End of Treatment (EOT) |
| Proportion of Subjects With Reduction of Intact Parathyroid Hormone (iPTH) of at Least 20% at Week 6 | Baseline to End of Treatment (6 weeks) | Proportion of subjects with at least 20% reduction in plasma intact parathyroid hormone (iPTH) and/or mean iPTH reduction to 70 pg/mL or less at End of Treatment (EOT) |
Countries
United States
Participant flow
Recruitment details
Subjects with Stage 3 chronic kidney disease, vitamin D insufficiency and secondary parahyperthyroidism were recruited from 16 sites within the US.
Pre-assignment details
This trial randomized 78 subjects. One subject in the 90 µg treatment arm was lost to follow-up after randomization but before receiving study drug. This subject was excluded from the Intent to Treat population (ITT).
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: CTAP101 Capsules 60µg Cohort 1 CTAP101 Capsules- 60µg: 60µg of CTAP101 capsules given once daily for 42 days. | 17 |
| Cohort 1: CTAP101 Capsules 90µg Cohort 1 CTAP101 Capsules - 90µg: 90µg of CTAP101 capsules given once daily for 42 days. | 16 |
| Cohort 1: Sugar Capsule Cohort 1 Matching Sugar Capsule: Placebo capsules given once daily for 42 days. | 17 |
| Cohort 2: CTAP101 Capsules 30µg Cohort 2 CTAP101 Capsules - 30µg: 30µg of CTAP101 capsules given once daily for 42 days. | 13 |
| Cohort 2: Sugar Capsule Cohort 2 Matching Sugar Capsule: Placebo capsules given once daily for 42 days. | 14 |
| Total | 77 |
Baseline characteristics
| Characteristic | Cohort 1: CTAP101 Capsules 60µg | Cohort 1: CTAP101 Capsules 90µg | Cohort 1: Sugar Capsule | Cohort 2: CTAP101 Capsules 30µg | Cohort 2: Sugar Capsule | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 64.7 years STANDARD_DEVIATION 9.2 | 64.6 years STANDARD_DEVIATION 11.41 | 61.9 years STANDARD_DEVIATION 17.79 | 58.2 years STANDARD_DEVIATION 16.14 | 63.9 years STANDARD_DEVIATION 11.47 | 63.0 years STANDARD_DEVIATION 13.39 |
| Sex: Female, Male Female | 7 Participants | 9 Participants | 13 Participants | 7 Participants | 7 Participants | 43 Participants |
| Sex: Female, Male Male | 10 Participants | 7 Participants | 4 Participants | 6 Participants | 7 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 22 / 31 | 8 / 13 | 12 / 17 | 10 / 16 |
| serious Total, serious adverse events | 1 / 31 | 1 / 13 | 1 / 17 | 1 / 16 |
Outcome results
Primary
Mean Percent Change From Baseline in Plasma Intact Parathyroid Hormone (iPTH) to End of Treatment (Per Protocol Population)
Mean percent change from baseline in plasma intact parathyroid hormone (iPTH) from baseline to End of Treatment (EOT) in the Per Protocol population. Subjects in Cohorts 1 and 2 (dose regimens 60/90 and 30 mcg, respectively) were compared to their respective placebo groups.
Time frame: 6 weeks
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: CTAP101 Capsules 60µg | Mean Percent Change From Baseline in Plasma Intact Parathyroid Hormone (iPTH) to End of Treatment (Per Protocol Population) | -32.77 percentage of change from baseline | Standard Deviation 22.778 |
| Cohort 1: CTAP101 Capsules 90µg | Mean Percent Change From Baseline in Plasma Intact Parathyroid Hormone (iPTH) to End of Treatment (Per Protocol Population) | -39.32 percentage of change from baseline | Standard Deviation 16.243 |
| Cohort 1: Sugar Capsule | Mean Percent Change From Baseline in Plasma Intact Parathyroid Hormone (iPTH) to End of Treatment (Per Protocol Population) | 20.49 percentage of change from baseline | Standard Deviation 52.871 |
| Cohort 2: CTAP101 Capsules 30µg | Mean Percent Change From Baseline in Plasma Intact Parathyroid Hormone (iPTH) to End of Treatment (Per Protocol Population) | -20.86 percentage of change from baseline | Standard Deviation 21.549 |
| Cohort 2: Sugar Capsule | Mean Percent Change From Baseline in Plasma Intact Parathyroid Hormone (iPTH) to End of Treatment (Per Protocol Population) | 13.18 percentage of change from baseline | Standard Deviation 30.185 |
p-value: <0.01Mixed effect model
Primary
Proportion (%) of Subjects With Serum 25-hydroxyvitamin D ≥30 ng/mL (PP).
The proportion of subjects in the per protocol population with serum 25-hydroxyvitamin D ≥30 ng/mL at End-of-Treatment (EOT; Week 6) in Cohorts 1 and 2 (60/90 and 30 μg groups, respectively) were compared to their corresponding placebo groups.
Time frame: 6 weeks
Population: Per protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: CTAP101 Capsules 60µg | Proportion (%) of Subjects With Serum 25-hydroxyvitamin D ≥30 ng/mL (PP). | 100 percentage of participants |
| Cohort 1: CTAP101 Capsules 90µg | Proportion (%) of Subjects With Serum 25-hydroxyvitamin D ≥30 ng/mL (PP). | 100 percentage of participants |
| Cohort 1: Sugar Capsule | Proportion (%) of Subjects With Serum 25-hydroxyvitamin D ≥30 ng/mL (PP). | 0 percentage of participants |
| Cohort 2: CTAP101 Capsules 30µg | Proportion (%) of Subjects With Serum 25-hydroxyvitamin D ≥30 ng/mL (PP). | 91.7 percentage of participants |
| Cohort 2: Sugar Capsule | Proportion (%) of Subjects With Serum 25-hydroxyvitamin D ≥30 ng/mL (PP). | 7.1 percentage of participants |
p-value: <0.0001Z-test cmpared 2 independ. proportions
Secondary
Change From Baseline in Serum 25-hydroxyvitamin D at Week 6
Mean absolute change from baseline in serum total 25-hydroxyvitamin D to end of treatment (EOT)
Time frame: Baseline to End of Treatment (6 weeks)
Population: Per protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: CTAP101 Capsules 60µg | Change From Baseline in Serum 25-hydroxyvitamin D at Week 6 | 43.25 ng/mL | Standard Deviation 16.519 |
| Cohort 1: CTAP101 Capsules 90µg | Change From Baseline in Serum 25-hydroxyvitamin D at Week 6 | 63.69 ng/mL | Standard Deviation 17.826 |
| Cohort 1: Sugar Capsule | Change From Baseline in Serum 25-hydroxyvitamin D at Week 6 | -0.65 ng/mL | Standard Deviation 2.502 |
| Cohort 2: CTAP101 Capsules 30µg | Change From Baseline in Serum 25-hydroxyvitamin D at Week 6 | 16.22 ng/mL | Standard Deviation 6.005 |
| Cohort 2: Sugar Capsule | Change From Baseline in Serum 25-hydroxyvitamin D at Week 6 | -1.89 ng/mL | Standard Deviation 4.913 |
p-value: <0.0001Mixed effect model
p-value: <0.01Mixed effect model
Secondary
Percent Change From Baseline in Serum 25-hydroxyvitamin D at End of Treatment (EOT, Week 6) in the Per Protocol Population
Mean percent change from baseline in serum 25-hydroxyvitamin D at End of Treatment (EOT, week 6) in the per protocol population. Subjects in Cohorts 1 and 2 (dose regimens of 60/90 and 30 mcg, respectively) were compared versus their corresponding placebo groups.
Time frame: Baseline to End of Treatment (6 weeks)
Population: Per protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: CTAP101 Capsules 60µg | Percent Change From Baseline in Serum 25-hydroxyvitamin D at End of Treatment (EOT, Week 6) in the Per Protocol Population | 187.64 percentage of change from baseline | Standard Deviation 74.251 |
| Cohort 1: CTAP101 Capsules 90µg | Percent Change From Baseline in Serum 25-hydroxyvitamin D at End of Treatment (EOT, Week 6) in the Per Protocol Population | 313.12 percentage of change from baseline | Standard Deviation 101.592 |
| Cohort 1: Sugar Capsule | Percent Change From Baseline in Serum 25-hydroxyvitamin D at End of Treatment (EOT, Week 6) in the Per Protocol Population | -2.67 percentage of change from baseline | Standard Deviation 13.069 |
| Cohort 2: CTAP101 Capsules 30µg | Percent Change From Baseline in Serum 25-hydroxyvitamin D at End of Treatment (EOT, Week 6) in the Per Protocol Population | 90.90 percentage of change from baseline | Standard Deviation 62.189 |
| Cohort 2: Sugar Capsule | Percent Change From Baseline in Serum 25-hydroxyvitamin D at End of Treatment (EOT, Week 6) in the Per Protocol Population | -7.22 percentage of change from baseline | Standard Deviation 20.599 |
p-value: <0.0001Mixed effect model
Secondary
Proportion of Subjects With Reduction of Intact Parathyroid Hormone (iPTH) of at Least 20% at Week 6
Proportion of subjects with at least 20% reduction in plasma intact parathyroid hormone (iPTH) and/or mean iPTH reduction to 70 pg/mL or less at End of Treatment (EOT)
Time frame: Baseline to End of Treatment (6 weeks)
Population: Per protocol population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: CTAP101 Capsules 60µg | Proportion of Subjects With Reduction of Intact Parathyroid Hormone (iPTH) of at Least 20% at Week 6 | 12 participants |
| Cohort 1: CTAP101 Capsules 90µg | Proportion of Subjects With Reduction of Intact Parathyroid Hormone (iPTH) of at Least 20% at Week 6 | 13 participants |
| Cohort 1: Sugar Capsule | Proportion of Subjects With Reduction of Intact Parathyroid Hormone (iPTH) of at Least 20% at Week 6 | 2 participants |
| Cohort 2: CTAP101 Capsules 30µg | Proportion of Subjects With Reduction of Intact Parathyroid Hormone (iPTH) of at Least 20% at Week 6 | 5 participants |
| Cohort 2: Sugar Capsule | Proportion of Subjects With Reduction of Intact Parathyroid Hormone (iPTH) of at Least 20% at Week 6 | 1 participants |
Comparison: The proportion of subjects achieving a ≥20% decrease in plasma iPTH at EOT was greater in the CTAP101 Capsules 60 and 90 μg groups compared to the corresponding placebo group.p-value: <0.001Z-test compared 2 independ. proportions
Secondary
Proportion of Subjects With Reduction of Intact Parathyroid Hormone (iPTH) of at Least 30% at Week 6
Proportion of subjects with at least 30% reduction in plasma intact parathyroid hormone (iPTH) and/or mean iPTH reduction to 70 pg/mL or less at End of Treatment (EOT)
Time frame: Baseline to End of Treatment (6 weeks)
Population: Per protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: CTAP101 Capsules 60µg | Proportion of Subjects With Reduction of Intact Parathyroid Hormone (iPTH) of at Least 30% at Week 6 | 11 participants |
| Cohort 1: CTAP101 Capsules 90µg | Proportion of Subjects With Reduction of Intact Parathyroid Hormone (iPTH) of at Least 30% at Week 6 | 9 participants |
| Cohort 1: Sugar Capsule | Proportion of Subjects With Reduction of Intact Parathyroid Hormone (iPTH) of at Least 30% at Week 6 | 2 participants |
| Cohort 2: CTAP101 Capsules 30µg | Proportion of Subjects With Reduction of Intact Parathyroid Hormone (iPTH) of at Least 30% at Week 6 | 5 participants |
| Cohort 2: Sugar Capsule | Proportion of Subjects With Reduction of Intact Parathyroid Hormone (iPTH) of at Least 30% at Week 6 | 0 participants |
p-value: <0.05Z-test compared 2 independ. proportions