Chronic Kidney Disease, Hyperparathyroidism, Secondary, Vitamin D Deficiency
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 evaluate the efficacy of CTAP101 Capsules versus placebo in reducing intact parathyroid hormone (iPTH) by at least 30% from pretreatment baseline; safety and tolerability of CTAP101 will also be evaluated
Detailed description
This is a phase 3, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of CTAP101 Capsules administered for 26 weeks to treat SHPT in subjects ≥18 years of age with stage 3 or 4 CKD and vitamin D insufficiency. The study will be conducted at approximately 40 sites within the United States (US). Approximately 550 subjects will be screened to randomize approximately 210 eligible subjects, stratified by CKD stage (approximately 105 subjects in each stage) in a 2:1 ratio to receive either CTAP101 Capsules or matching placebo. An Interactive Voice Response System (IVRS) will provide study treatment group assignments using the computer-generated randomization code provided by the IVRS vendor. Subjects will receive an initial daily dose of 1 capsule (CTAP101 Capsules, 30 µg, or matching placebo) for the first 12 weeks. After l2 weeks (visit 8) and per pre-defined criteria, the dose may be increased in a blinded fashion by the IVRS with oversight by an independent medical monitor.
Interventions
CTAP101 30 μg capsule taken daily at bedtime
Sugar pill capsule (placebo to CTAP101 30 μg capsule) taken daily at bedtime.
Sponsors
OPKO IP Holdings II, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Urinary albumin excretion ≤ 3000 mcg/mg of creatinine 2. Stage 3 or 4 CKD 3. Plasma iPTH: ≥ 85 pg/mL and \< 500 pg/mL 4. Serum Ca: ≥ 8.4 mg/dL and \< 9.8 mg/dL 5. Serum P: ≥ 2.0 mg/dL and \< 5.0 mg/dL 6. Serum 25-hydroxyvitamin D: ≥ 10 ng/mL and \< 30 ng/mL. 7. Stable dose of Vitamin D therapy ≤ 1600 IU/day and receiving same dose for at least 2 months
Exclusion criteria
1. History of kidney transplant or parathyroidectomy 2. Spot urine calcium:creatinine ratio \> 0.2 (\>200 mg/g Cr) 3. Current serious illness, such as malignancy, HIV, liver disease, cardiovascular event or hepatitis 4. Currently on dialysis 5. Use of pharmacological dose of ergocalciferol or cholecalciferol (≥ 50,000 IU mcg per month) during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants in the Intent to Treat Population With Decrease in Plasma Intact Parathyroid Hormone (iPTH) of ≥30% From Pre-treatment Baseline | Approximately 6 months | Number of subjects in the intent to treat population attaining mean decrease in plasma intact Parathyroid Hormone (iPTH) of ≥30% from P\\pre-treatment baseline in the efficacy assessment phase (EAP) referred to as responders |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants in the Per Protocol Population With Decrease in Plasma Intact Parathyroid Hormone (iPTH) of ≥30% From Pre-treatment Baseline | Approximately 6 months | Number of subjects in the per protocol population attaining a mean decrease in plasma intact parathyroid hormone (iPTH) of ≥30% from pre-treatment baseline in the efficacy assessment phase (EAP), referred to as responders |
| Subjects in the Intent to Treat Population With Normal Serum Total 25-hydroxyvitamin D | Approximately 6 months | Subjects in the intent to treat population with normal serum total 25-hydroxyvitamin D (\>/= 30 ng/dL) |
| Subjects in the Per Protocol Population With Normal Serum Total 25-hydroxyvitamin D | Approximately 6 months | Subjects in the per protocol population with normal serum total 25-hydroxyvitamin D (\>/= 30 ng/mL) |
Countries
United States
Participant flow
Recruitment details
This multicenter study was conducted at 45 investigational sites within the US. Subjects were enrolled and treated from 04 February 2013 through 13 August 2014.
Pre-assignment details
Subjects were stratified by CKD stage and were randomized in a 2:1 ratio to receive a daily 30 μg oral dose of CTAP101 capsules (or matching placebo) for 12 weeks at bedtime. Subjects presenting on a regimen of bone metabolism therapy were to discontinue their prior treatment for at least 28 days' washout (except for bisphosphonates).
Participants by arm
| Arm | Count |
|---|---|
| Sugar Pill to CTAP101 30 μg 1 sugar pill to CTAP101 30 μg capsule daily at bedtime for 12 weeks, with an increase to 2 sugar pills to CTAP101 30 μg capsules daily at bedtime for weeks 13-26.
Sugar pill to CTAP101 30 μg capsules: Sugar pill capsule (placebo to CTAP101 30 μg capsule) taken daily at bedtime. | 72 |
| CTAP101 30 μg Capsules 1 CTAP101 30 μg capsule daily at bedtime for 12 weeks, with a possible increase to 2 CTAP101 30 μg capsules daily at bedtime for study duration, if needed (26 weeks total). Subjects not requiring a dose increase after 12 weeks would receive 1 CTAP101 30 μg capsule and one sugar pill (to CTAP101 30 μg capsule) for weeks 13-26.
CTAP101 30 μg capsules: CTAP101 30 μg capsule taken daily at bedtime
Sugar pill to CTAP101 30 μg capsules: Sugar pill capsule (placebo to CTAP101 30 μg capsule) taken daily at bedtime. | 144 |
| Total | 216 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 7 |
| Overall Study | Lost to Follow-up | 2 | 5 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Serum Calcium >/= 11.0 mg/dL, repeat con | 0 | 1 |
| Overall Study | Subject noncompliance | 2 | 3 |
| Overall Study | Withdrawal by Subject | 5 | 7 |
Baseline characteristics
| Characteristic | Sugar Pill to CTAP101 30 μg | CTAP101 30 μg Capsules | Total |
|---|---|---|---|
| Age, Continuous | 65.3 years STANDARD_DEVIATION 10.06 | 66.8 years STANDARD_DEVIATION 10.9 | 66.3 years STANDARD_DEVIATION 10.63 |
| Region of Enrollment United States | 72 participants | 144 participants | 216 participants |
| Sex: Female, Male Female | 39 Participants | 71 Participants | 110 Participants |
| Sex: Female, Male Male | 33 Participants | 73 Participants | 106 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 72 | 32 / 144 |
| serious Total, serious adverse events | 11 / 72 | 22 / 144 |
Outcome results
Primary
Number of Participants in the Intent to Treat Population With Decrease in Plasma Intact Parathyroid Hormone (iPTH) of ≥30% From Pre-treatment Baseline
Number of subjects in the intent to treat population attaining mean decrease in plasma intact Parathyroid Hormone (iPTH) of ≥30% from P\\pre-treatment baseline in the efficacy assessment phase (EAP) referred to as responders
Time frame: Approximately 6 months
Population: Intent to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sugar Pill to CTAP101 30 μg | Number of Participants in the Intent to Treat Population With Decrease in Plasma Intact Parathyroid Hormone (iPTH) of ≥30% From Pre-treatment Baseline | 5 participants |
| CTAP101 30 μg Capsules | Number of Participants in the Intent to Treat Population With Decrease in Plasma Intact Parathyroid Hormone (iPTH) of ≥30% From Pre-treatment Baseline | 49 participants |
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Number of Participants in the Per Protocol Population With Decrease in Plasma Intact Parathyroid Hormone (iPTH) of ≥30% From Pre-treatment Baseline
Number of subjects in the per protocol population attaining a mean decrease in plasma intact parathyroid hormone (iPTH) of ≥30% from pre-treatment baseline in the efficacy assessment phase (EAP), referred to as responders
Time frame: Approximately 6 months
Population: Per protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sugar Pill to CTAP101 30 μg | Number of Participants in the Per Protocol Population With Decrease in Plasma Intact Parathyroid Hormone (iPTH) of ≥30% From Pre-treatment Baseline | 5 participants |
| CTAP101 30 μg Capsules | Number of Participants in the Per Protocol Population With Decrease in Plasma Intact Parathyroid Hormone (iPTH) of ≥30% From Pre-treatment Baseline | 47 participants |
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Subjects in the Intent to Treat Population With Normal Serum Total 25-hydroxyvitamin D
Subjects in the intent to treat population with normal serum total 25-hydroxyvitamin D (\>/= 30 ng/dL)
Time frame: Approximately 6 months
Population: Intent to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sugar Pill to CTAP101 30 μg | Subjects in the Intent to Treat Population With Normal Serum Total 25-hydroxyvitamin D | 5 participants |
| CTAP101 30 μg Capsules | Subjects in the Intent to Treat Population With Normal Serum Total 25-hydroxyvitamin D | 120 participants |
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Subjects in the Per Protocol Population With Normal Serum Total 25-hydroxyvitamin D
Subjects in the per protocol population with normal serum total 25-hydroxyvitamin D (\>/= 30 ng/mL)
Time frame: Approximately 6 months
Population: Per protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sugar Pill to CTAP101 30 μg | Subjects in the Per Protocol Population With Normal Serum Total 25-hydroxyvitamin D | 5 participants |
| CTAP101 30 μg Capsules | Subjects in the Per Protocol Population With Normal Serum Total 25-hydroxyvitamin D | 116 participants |
p-value: <0.0001Cochran-Mantel-Haenszel