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

A Multi-Center, Randomized, Two-Cohort Phase 2 Study to Evaluate the Safety, Efficacy,
Pharmacokinetics and Pharmacodynamics of CTAP101 (calcifediol) Extended-Release Capsules to
Treat Secondary Hyperparathyroidism in Subjects with Vitamin D Insufficiency and Chronic
Kidney Disease Requiring Regular Hemodialysis.

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.

3. 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.

4. Be receiving calcimimetic therapy (either etelcalcetide or cinacalcet) plus calcitriol
or calcimimetic therapy plus another 1-alpha-hydroxylated vitamin D analog
(paricalcitol or doxercalciferol) for at least 1 month at the time of screening for
enrollment in Cohort 1. For Cohort 2, at least 40% of enrolled subjects must have been
receiving calcimimetic therapy plus calcitriol or other 1α -hydroxylated vitamin D
analog for at least 1 month at the time of screening.

5. Exhibit during the initial screening visit:

Cohort 1:

1. Plasma iPTH ≥150 pg/mL and <400 pg/mL; and

2. Serum total 25-hydroxyvitamin D <30 ng/mL if not receiving vitamin D
supplementation at a rate >1,700 IU per day or 50,000 IU/1,250 mcg per month.

Cohort 2:

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 active vitamin D analog; and,

3. Serum total 25-hydroxyvitamin D <30 ng/mL if not receiving vitamin D
supplementation at a rate >1,700 IU per day or 50,000 IU/1,250 mcg per month.

6. Must forgo any further treatment with etelcalcetide and cinacalcet for the duration of
the study and undergo an 8-week washout period.

7. Must forgo any further treatment with calcitriol or other 1α-hydroxylated vitamin D
analogs for the duration of the study and undergo an 8-week washout period.

8. If taking vitamin D supplementation at a rate of >1,700 IU per day or 50,000 IU/1,250
mcg per month, must reduce the dose to ≤1,700 IU per day for the duration of the study
and undergo an 8-week washout period.

9. 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 at a rate of >1,700 IU per day or 50,000 IU/1,250 mcg per
month):

Cohort 1:

Plasma iPTH increased by at least 50% and ≥450 pg/mL and <900 pg/mL; or,

Cohort 2:

1. Plasma iPTH ≥300 pg/mL and <900 pg/mL (approximately half of the subjects will be
enrolled in each of these two iPTH strata: ≥300 to <600 and ≥600 to <900 pg/mL);
and

Cohorts 1 and 2:

2. Corrected serum calcium <9.8 mg/dL;

3. Serum total 25-hydroxyvitamin D <30 ng/mL; and,

4. Serum phosphorus <6.5 mg/dL.

10. 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.

11. If taking bone metabolism therapies that may interfere with study endpoints, must
discontinue use of these agents for the duration of the study.

12. Willing and able to comply with study instructions and commit to all clinic visits for
the duration of the study.

13. 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.

14. 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.

15. Be able to read, understand and sign the subject Informed Consent Form (ICF) or have a
legal representative sign the ICF.

Exclusion Criteria:

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

1. History of or planned kidney transplant or parathyroidectomy.

2. 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-hydroyxlated vitamin D analog.

3. Receipt of bisphosphonate therapy or other bone modifying treatment (eg, denosumab)
within 6 months prior to enrollment.

4. 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.

5. 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.

6. Known or suspected hypersensitivity to any of the constituents of the study drugs.

7. Currently participating in, or has participated in, an interventional/investigational
study within 30 days prior to study screening.