Extension Study of CTAP101-CL-3001 or CTAP101-CL-3002

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Long-term Safety and Efficacy Study of CTAP101 Capsules in Subjects With Stages 3 or 4 Chronic Kidney Disease, Secondary Hyperparathyroidism and Vitamin D Insufficiency (Extension of Study CTAP101-CL-3001 or CTAP101-CL-3002)

Conditions
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Vitamin D Deficiency, Chronic Kidney Disease, Hyperparathyroidism, Secondary

Intervention / Treatment
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* Drug: CTAP101 Capsules
* Drug: Calcitriol
* Drug: Doxercalciferol
* Drug: Paricalcitol


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CTAP101 Capsules alone<br>CTAP101 Capsules 30 or 60 mcg daily for up to 26 weeks | Drug: CTAP101 Capsules<br>* At week 12, eligible subjects will continue to take 1-2 capsules (30 mcg each capsule) CTAP101 daily<br>* Other names: Calcifediol;|
| Experimental: CTAP101 Capsules +calcitriol<br>CTAP101 Capsules 60 mcg +calcitriol daily for 14 weeks | Drug: CTAP101 Capsules<br>* At week 12, eligible subjects will continue to take 1-2 capsules (30 mcg each capsule) CTAP101 daily<br>* Other names: Calcifediol;Drug: Calcitriol<br>* At week 12, eligible subjects will be randomized to also take calcitriol 0.25 mcg dose one capsule daily<br>* Other names: calcifediol;|
| Experimental: CTAP101 Capsules +doxercalciferol<br>CTAP101 Capsules 60 mcg +doxercalciferol daily for 14 weeks | Drug: CTAP101 Capsules<br>* At week 12, eligible subjects will continue to take 1-2 capsules (30 mcg each capsule) CTAP101 daily<br>* Other names: Calcifediol;Drug: Doxercalciferol<br>* At week 12, eligible subjects will be randomized to also take doxercalciferol 0.5 mcg one capsule daily<br>* Other names: calcifediol;|
| Experimental: CTAP101 Capsules +paricalcitol<br>CTAP101 Capsules 60 mcg +paricalcitol daily for 14 weeks | Drug: CTAP101 Capsules<br>* At week 12, eligible subjects will continue to take 1-2 capsules (30 mcg each capsule) CTAP101 daily<br>* Other names: Calcifediol;Drug: Paricalcitol<br>* At week 12, eligible subjects will be randomized to also take paricalcitol 1 mcg one capsule daily<br>* Other names: calcifediol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | up to 6 months | 
| 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) | up to 6 months | 
| 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) | up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parathyroid Diseases, Renal Insufficiency, Kidney Failure, Chronic, Hyperparathyroidism, Secondary, Vitamin D, Hyperparathyroidism, Kidney Diseases, Kidney Failure, Renal Insufficiency, Chronic