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 extension study of subjects previously enrolled in studies CTAP101-CL-3001 or CTAP101-CL-3002 allows long term evaluation of the safety and efficacy of CTAP101 Capsules in reducing elevated intact parathyroid hormone (iPTH) and correcting vitamin D insufficiency in stage 3 or 4 chronic kidney disease patients.
Detailed description
Only subjects previously enrolled in studies CTAP101-CL-3001 or CTAP101-CL-3002 are eligible to participate in this extension study. This is a phase 3, open-label study of CTAP101 Capsules, with and without add-on vitamin D hormone therapy.
Interventions
DRUGCTAP101 Capsules
At week 12, eligible subjects will continue to take 1-2 capsules (30 mcg each capsule) CTAP101 daily
DRUGCalcitriol
At week 12, eligible subjects will be randomized to also take calcitriol 0.25 mcg dose one capsule daily
DRUGDoxercalciferol
At week 12, eligible subjects will be randomized to also take doxercalciferol 0.5 mcg one capsule daily
DRUGParicalcitol
At week 12, eligible subjects will be randomized to also take paricalcitol 1 mcg one capsule daily
Sponsors
OPKO Health, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Completed either of the phase 3 double-blind, placebo-controlled studies, CTAP101-CL-3001 or CTAP101-CL-3002 * Taking no more than 1000 mg/day of elemental Ca and willing/able to remain on this dose for the duration of the study * Taking no more than 1600 IU/dose vitamin D (ergocalciferol or cholecalciferol) therapy and willing/able to remain on a stable dose of vitamin D during the study * Willing and able to comply with study instructions and to commit to all clinic visits for the duration of the study * Female subjects of childbearing potential must be neither pregnant nor lactating and must have a negative urine pregnancy test * All female subjects of childbearing potential and male subjects with female partners of childbearing potential must agree to use effective contraception (eg, implants, injectables, combined oral contraceptives, intrauterine device, sexual abstinence, vasectomy or vasectomized partner) for the duration of the study * Have the ability to read and understand subject Informed Consent Form (ICF). Subjects or their legal representatives must sign the ICF.
Exclusion criteria
* Use of pharmacological dose of ergocalciferol and cholecalciferol (monthly equivalent of 50,000 IU or 1250 µg, eg, Drisdol®) or bisphosphonate therapy * Use of other bone metabolism therapy (with the exception of stable doses of bisphosphonates and denosumab \[Xgeva® and Prolia®\]) that may interfere with study endpoints * Concomitant serious illness or medical condition, such as malignancy, human immunodeficiency virus, significant gastrointestinal or hepatic disease or cardiovascular event or hepatitis that in the opinion of the investigator may worsen and/or interfere with participation in the study * Neurological/psychiatric disorder, including psychotic disorder or dementia, or any condition reason which, in the opinion of the investigator makes adherence to a treatment or follow-up schedule unlikely * Known or suspected hypersensitivity to any of the constituents of either investigational product (CTAP101) or adjunctive vitamin D hormone therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants in the Intent to Treat Population With a Mean Reduction in Plasma Intact Parathyroid Hormone (iPTH) of >/= 30% From Baseline Values at End of Treatment (EOT) | up to 6 months | Number of subjects in the intent to treat population with a mean reduction in plasma intact parathyroid hormone (iPTH) of \>/= 30% from pretreatment baseline values at end of treatment (EOT), classified as responders |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants in the Per Protocol Population With NormalSerum 25-hydroxyvitamin D at End of Treatment (EOT) | up to 6 months | Number of Participants in the per protocol population with serum 25-hydroxyvitamin D \>/= 30 ng/mL at End of Treatment (EOT) |
| Number of Participants in the Per Protocol Population With Mean Reduction in Plasma Intact Parathyroid Hormone (iPTH) of >/= 30% From Baseline Values at End of Treatment (EOT) | up to 6 months | Number of subjects in the per protocol population with a mean reduction in plasma intact parathyroid hormone (iPTH) of \>/= 30% from pretreatment baseline values at end of treatment (EOT), classified as responders |
| Number of Participants in the Intent to Treat Population With Normal Serum 25-hydroxyvitamin D at End of Treatment (EOT) | up to 6 months | Number of Participants in the Intent to Treat Population with serum 25-hydroxyvitamin D \>/= 30 ng/mL at End of Treatment (EOT) |
Participant flow
Recruitment details
Subjects could enroll in extension study after completing trials CTAP101-CL-3001 or CTAP101-CL-3002. Subjects from 68 sites participated with at least 1 subject enrolled in the extension per site. Three sites participated in both blinded trials.
Pre-assignment details
Treatment groups were categorized as treated for 26 weeks; subjects previously on placebo in predecessor trials) or 12 months (52 weeks; subjects previously on active treatment in predecessor trials). Following 12 weeks, a subset of eligible subjects (n=up to 90) could be randomized to take adjunctive therapy in addition to CTAP101 capsules.
Participants by arm
| Arm | Count |
|---|---|
| CTAP101 Capsules (Not Randomized; 6 Mos Treatment) CTAP101 Capsules 30 or 60 mcg daily for up to 12 weeks, followed by additional weeks 13-26.
CTAP101 Capsules: At end of week 12, eligible subjects will continue to take 1 or 2 capsules (30 mcg each capsule) CTAP101 daily. | 103 |
| CTAP101 Capsules (Monotherapy; 12 Mos Treatment) CTAP101 Capsules 30 or 60 mcg daily for up to 12 weeks followed by additional weeks 13-26.
CTAP101 Capsules: At end of week 12, eligible subjects will continue to take 1 or 2 capsules (30 mcg each capsule) CTAP101 daily | 153 |
| CTAP101 Caps 2 x 30 mcg Daily for 12 wk+Adjunctive CTAP101 Capsules 2 x 30 mcg daily for up to 12 weeks. At week 12, a subset of eligible subjects (N=85) were randomized to take adjunctive therapy (calcitriol 0.25 mcg or doxercalciferol 0.5 mcg or paricalcitol 1 mcg) daily in addition to the CTAP101 capsules. | 42 |
| Total | 298 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative reasons | 0 | 1 | 0 |
| Overall Study | Adverse Event | 3 | 10 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 3 | 1 |
| Overall Study | Serum Ca >/=11.0mg/dL | 1 | 0 | 0 |
| Overall Study | Subject non-compliance | 1 | 4 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 5 | 0 |
Baseline characteristics
| Characteristic | CTAP101 Capsules (Not Randomized; 6 Mos Treatment) | CTAP101 Capsules (Monotherapy; 12 Mos Treatment) | CTAP101 Caps 2 x 30 mcg Daily for 12 wk+Adjunctive | Total |
|---|---|---|---|---|
| Age, Continuous | 64.7 years STANDARD_DEVIATION 10.78 | 66.9 years STANDARD_DEVIATION 9.83 | 65.0 years STANDARD_DEVIATION 12.34 | 65.9 years STANDARD_DEVIATION 10.56 |
| Region of Enrollment United States | 103 participants | 153 participants | 42 participants | 298 participants |
| Sex: Female, Male Female | 55 Participants | 85 Participants | 14 Participants | 154 Participants |
| Sex: Female, Male Male | 48 Participants | 68 Participants | 28 Participants | 144 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 36 / 103 | 54 / 153 | 22 / 42 |
| serious Total, serious adverse events | 18 / 103 | 33 / 153 | 9 / 42 |
Outcome results
Primary
Number of Participants in the Intent to Treat Population With a Mean Reduction in Plasma Intact Parathyroid Hormone (iPTH) of >/= 30% From Baseline Values at End of Treatment (EOT)
Number of subjects in the intent to treat population with a mean reduction in plasma intact parathyroid hormone (iPTH) of \>/= 30% from pretreatment baseline values at end of treatment (EOT), classified as responders
Time frame: up to 6 months
Population: Intent to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CTAP101 Capsules (Not Randomized; 6 Mos Treatment) | Number of Participants in the Intent to Treat Population With a Mean Reduction in Plasma Intact Parathyroid Hormone (iPTH) of >/= 30% From Baseline Values at End of Treatment (EOT) | 34 participants |
| CTAP101 Capsules (Not Randomized; 12 Mos Treatment) | Number of Participants in the Intent to Treat Population With a Mean Reduction in Plasma Intact Parathyroid Hormone (iPTH) of >/= 30% From Baseline Values at End of Treatment (EOT) | 66 participants |
| CTAP101 Caps 2 x 30 mcg Daily for 12 wk+Adjunctive | Number of Participants in the Intent to Treat Population With a Mean Reduction in Plasma Intact Parathyroid Hormone (iPTH) of >/= 30% From Baseline Values at End of Treatment (EOT) | 30 participants |
p-value: 0.1041Cochran-Mantel-Haenszel
Secondary
Number of Participants in the Intent to Treat Population With Normal Serum 25-hydroxyvitamin D at End of Treatment (EOT)
Number of Participants in the Intent to Treat Population with serum 25-hydroxyvitamin D \>/= 30 ng/mL at End of Treatment (EOT)
Time frame: up to 6 months
Population: Intent to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CTAP101 Capsules (Not Randomized; 6 Mos Treatment) | Number of Participants in the Intent to Treat Population With Normal Serum 25-hydroxyvitamin D at End of Treatment (EOT) | 87 participants |
| CTAP101 Capsules (Not Randomized; 12 Mos Treatment) | Number of Participants in the Intent to Treat Population With Normal Serum 25-hydroxyvitamin D at End of Treatment (EOT) | 124 participants |
| CTAP101 Caps 2 x 30 mcg Daily for 12 wk+Adjunctive | Number of Participants in the Intent to Treat Population With Normal Serum 25-hydroxyvitamin D at End of Treatment (EOT) | 38 participants |
p-value: 0.4817Cochran-Mantel-Haenszel
Secondary
Number of Participants in the Per Protocol Population With Mean Reduction in Plasma Intact Parathyroid Hormone (iPTH) of >/= 30% From Baseline Values at End of Treatment (EOT)
Number of subjects in the per protocol population with a mean reduction in plasma intact parathyroid hormone (iPTH) of \>/= 30% from pretreatment baseline values at end of treatment (EOT), classified as responders
Time frame: up to 6 months
Population: Per protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CTAP101 Capsules (Not Randomized; 6 Mos Treatment) | Number of Participants in the Per Protocol Population With Mean Reduction in Plasma Intact Parathyroid Hormone (iPTH) of >/= 30% From Baseline Values at End of Treatment (EOT) | 34 participants |
| CTAP101 Capsules (Not Randomized; 12 Mos Treatment) | Number of Participants in the Per Protocol Population With Mean Reduction in Plasma Intact Parathyroid Hormone (iPTH) of >/= 30% From Baseline Values at End of Treatment (EOT) | 64 participants |
| CTAP101 Caps 2 x 30 mcg Daily for 12 wk+Adjunctive | Number of Participants in the Per Protocol Population With Mean Reduction in Plasma Intact Parathyroid Hormone (iPTH) of >/= 30% From Baseline Values at End of Treatment (EOT) | 29 participants |
p-value: 0.0503Cochran-Mantel-Haenszel
Secondary
Number of Participants in the Per Protocol Population With NormalSerum 25-hydroxyvitamin D at End of Treatment (EOT)
Number of Participants in the per protocol population with serum 25-hydroxyvitamin D \>/= 30 ng/mL at End of Treatment (EOT)
Time frame: up to 6 months
Population: Per protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CTAP101 Capsules (Not Randomized; 6 Mos Treatment) | Number of Participants in the Per Protocol Population With NormalSerum 25-hydroxyvitamin D at End of Treatment (EOT) | 86 participants |
| CTAP101 Capsules (Not Randomized; 12 Mos Treatment) | Number of Participants in the Per Protocol Population With NormalSerum 25-hydroxyvitamin D at End of Treatment (EOT) | 120 participants |
| CTAP101 Caps 2 x 30 mcg Daily for 12 wk+Adjunctive | Number of Participants in the Per Protocol Population With NormalSerum 25-hydroxyvitamin D at End of Treatment (EOT) | 37 participants |
p-value: 0.8086Cochran-Mantel-Haenszel