Safety, Efficacy, PK and PD of CTAP101 (Calcifediol) ER Capsules for SHPT in HD Patients VDI

Inclusion Criteria:

Each subject must meet the following criteria to be enrolled into the two cohorts of this study:

1. Be at least 18 years of age.
2. Be diagnosed with CKD requiring in-center HD tiw for the preceding 6 months, as confirmed by medical history.

Be without any disease state or physical condition that might impair evaluation of safety or which, in the investigator's opinion, would interfere with study participation, including:

1. Serum albumin ≤ 3.0 g/dL; and,
2. Serum transaminase (alanine transaminase [ALT], glutamic pyruvic transaminase [SGPT], aspartate aminotransferase [AST] or glutamic oxaloacetic transaminase [SGOT]) > 2.5 times the upper limit of normal at screening.
3. Be receiving calcimimetic therapy (either etelcalcetide or cinacalcet) and/or calcitriol or other 1α-hydroxylated vitamin D analog (paricalcitol or doxercalciferol) for at least 1 month at the time of screening for enrollment. At least 50% of enrolled subjects will have been receiving calcimimetic therapy.

Exhibit during the initial screening visit:

1. Plasma iPTH ≥150 pg/mL and <600 pg/mL if receiving etelcalcetide, cinacalcet, calcitriol or other 1α-hydroxylated vitamin D analog (paricalcitol or doxercalciferol); or
2. Plasma iPTH ≥300 pg/mL and <900 pg/mL if not receiving etelcalcetide, cinacalcet, calcitriol or other 1α-hydroxylated vitamin D analog; and,
3. Serum total 25-hydroxyvitamin D <30 ng/mL if not receiving vitamin D supplementation.
4. When otherwise confirmed eligible at Visit 1, must forgo any further treatment with etelcalcetide and cinacalcet for the duration of the study and undergo an 8-week washout period.
5. When otherwise confirmed eligible at Visit 1, must forgo any further treatment with calcitriol or other 1α-hydroxylated vitamin D analogs or vitamin D supplements for the duration of the study and undergo an 8-week washout period.

Exhibit after the 8-week washout period (if required due to prior use of etelcalcetide, cinacalcet, calcitriol or other 1α-hydroxylated vitamin D analogs, or vitamin D supplementation):

Cohort 1:

1. Plasma iPTH increased by at least 50%; and,
2. Plasma iPTH ≥300 pg/mL and <1,200 pg/mL; or,

Cohort 2:

a. Plasma iPTH ≥300 pg/mL and <1,200 pg/mL (approximately half of the subjects will be enrolled in each of these two iPTH strata: ≥300 to <600 and ≥600 to <1,200 pg/mL); and

Cohorts 1 and 2:

1. Corrected serum calcium <9.8 mg/dL;
2. Serum total 25-hydroxyvitamin D <30 ng/mL; and,
3. Serum phosphorus <6.5 mg/dL.
4. When otherwise confirmed eligible at Visit 1, if taking more than 1,000 mg per day of elemental calcium, reduce calcium use (to ≤1,000 mg per day) and/or use non-calcium based phosphate binder therapies (as needed) for the duration of the study.
5. When otherwise confirmed eligible at Visit 1, if taking bone metabolism therapies that may interfere with study endpoints, must discontinue use of these agents for the duration of the study.
6. Willing and able to comply with study instructions and commit to all clinic visits for the duration of the study.
7. Female subjects of childbearing potential must be neither pregnant nor lactating and must have a negative serum beta-human chorionic gonadotropin (b-hCG) pregnancy test at the first screening visit and at other scheduled times.
8. 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.
9. Be able to read, understand and sign the subject Informed Consent Form (ICF) or have a legal representative sign the ICF.

4.3 Exclusion Criteria

Subjects who meet any of the following criteria will be excluded from the study:

Scheduled kidney transplant or parathyroidectomy.

History (prior 2 months) of corrected serum calcium ≥9.8 mg/dL or serum phosphorus

≥6.5 mg/dL if not receiving calcitriol or other 1α-hydroxylated vitamin D analog.

1. Receipt of bisphosphonate therapy or other bone modifying treatment (eg, denosumab) within 6 months prior to enrollment.
2. 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.
3. 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.
4. Known or suspected hypersensitivity to any of the constituents of the study drugs.
5. Currently participating in, or has participated in, an interventional/investigational study within 30 days prior to study screening.