Repeated-dose Safety, Efficacy, Pharmacokinetic and Pharmacodynamic of CTAP101, Immediate-release Calcifediol, High-dose Cholecalciferol, and Paricalcitol Plus Low-dose Cholecalciferol in Patients With Secondary Hyperparathyroidism, Chronic Kidney Disease 3-4 and Vitamin D Insufficiency
Condition: Secondary Hyperparathyroidism Due to Renal Causes; Vitamin D Insufficiency; CKD Stage 3; CKD Stage 4
MeSH terms: Neoplasm Metastasis; Kidney Diseases; Renal Insufficiency, Chronic; Hyperparathyroidism; Hyperparathyroidism, Secondary
Intervention: Calcifediol Oral Capsule; Calcifediol Oral Product; Cholecalciferol; Paricalcitol Oral Capsule
Intervention description: Capsule, daily; Capsule, once a month; Capsule, once a month; Capsule, daily
Intervention MeSH terms: Cholecalciferol; Vitamin D; Calcifediol
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 69.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      An Open-Label, Repeated-Dose Safety, Efficacy, Pharmacokinetic and Pharmacodynamic Study of
      Oral CTAP101 Capsules, Immediate- Release (IR) Calcifediol, High-Dose Cholecalciferol, and
      Paricalcitol Plus Low-Dose Cholecalciferol in Patients with Secondary Hyperparathyroidism,
      Stage 3 or 4 Chronic Kidney Disease and Vitamin D Insufficiency
    

Eligibility criteria:

        Inclusion Criteria:

          1. Be at least 18 years of age.

          2. Have stage 3 or 4 CKD (estimated glomerular filtration rate [eGFR] of ≥15 to <60
             millilter per minute per 1.73 meter square (mL/min/1.73 m2) using the Modification of
             Diet in Renal Disease equation).

          3. Be without any disease state or physical condition that might impair evaluation of
             safety and efficacy or which, in the Investigator's opinion, would interfere with
             study participation, including:

               1. Serum albumin ≤ 3.0 (grams per deciliter (g/dL);

               2. Serum transaminase (alanine transaminase, glutamic pyruvic transaminase,
                  aspartate aminotransferase or glutamic oxaloacetic transaminase) > 2.5 times the
                  upper limit of normal at screening; and,

               3. Urinary albumin excretion ≤3000 microgram per milligram (μg/mg) creatinine.

          4. Exhibit during the initial screening visit:

               1. Plasma intact parathyroid hormone (iPTH) ≥70 picogram per milliliter (pg/mL) and
                  <400 pg/mL if receiving calcitriol or other 1α- hydroxylated vitamin D analog
                  (paricalcitol or doxercalciferol); or

               2. Plasma iPTH ≥100 pg/mL and <500 pg/mL if not receiving calcitriol or other 1α-
                  hydroxylated vitamin D analog; and,

               3. Serum total 25-hydroxyvitamin D <30 nanogram per milliliter (ng/mL).

          5. If taking calcitriol, other 1α-hydroxylated vitamin D analog, or vitamin D
             supplementation, must forgo treatment with these non-study agents for the duration of
             the study and undergo a 4-week washout period.

          6. Exhibit after the 4-week washout period (if required):

               1. Plasma iPTH ≥100 pg/mL and <500 pg/mL;

               2. Corrected serum calcium <9.8 mg/dL; (corrected for serum albumin)

               3. Serum total 25-hydroxyvitamin D <30 nanogram per milliliter (ng/mL); and,

               4. Serum phosphorus <5.5 milligram per deciliter (mg/dL).

          7. If taking more than 1,500 milligram per day (mg/day) of elemental calcium, reduce
             calcium use (to approximately 1,000 to ≤1,500 mg/day) for the duration of the study.

          8. Willing and able to comply with study instructions and commit to all clinic visits for
             the duration of the study.

          9. Female subjects of childbearing potential must be neither pregnant nor lactating and
             must have negative blood pregnancy tests at the first screening visit.

         10. All female subjects of childbearing potential and male subjects with female partners
             of childbearing potential must agree to use effective contraception (implants,
             injectables, combined oral contraceptives, intrauterine device, sexual abstinence,
             vasectomy or vasectomized partner) for the duration of the study.

         11. Be able to read, understand and sign the subject Informed Consent Form (ICF) or have a
             legal authorized representative (LAR) sign the ICF.

        Exclusion Criteria:

          1. History of or planned kidney transplant or parathyroidectomy

          2. History (prior 3 months) of corrected serum calcium ≥9.8 mg/dL or serum phosphorus
             ≥5.5 mg/dL if not receiving calcitriol or other 1α-hydroxylated vitamin D analog.

          3. Need for phosphate binders to maintain the serum phosphate < 5.5 mg/dL or use of
             phosphate binders within 4 weeks prior to screening

          4. Use of calcimimetic therapy (cinacalcet or etelcalcetide) within 12 weeks of
             screening.

          5. Receipt of bisphosphonate therapy or other bone modifying treatment within 6 months
             prior to enrollment.

          6. Known previous or concomitant serious illness or medical condition, such as
             malignancy, human immunodeficiency virus, significant gastrointestinal or hepatic
             disease, intestinal malabsorption disorder, hepatitis or cardiovascular event that in
             the opinion of the Investigator may worsen or reduce life expectancy, and/or interfere
             with participation in the study.

          7. History of neurological/psychiatric disorder, including psychotic disorder or
             dementia, or any reason which, in the opinion of the Investigator makes adherence to a
             treatment or follow-up schedule unlikely.

          8. Known or suspected hypersensitivity to any of the constituents of the study drugs.

          9. Currently participating in, or has participated in, an interventional/investigational
             study within 30 days prior to study screening.