Pharmacokinetics, Pharmacodynamics, Safety and Tolerability Evaluation of CTAP101 Extended-release Capsules in Pediatric Participants

An Open-Label, Randomized, Multiple-Dose, Multi-Center Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of CTAP101 Extended-release Capsules in Pediatric Participants <18 Years of Age With Secondary Hyperparathyroidism, Stage 3 or 4 Chronic Kidney Disease and Vitamin D Insufficiency

The goal of this clinical trial is to evaluate safety, tolerability, and how CTAP101 Capsules work to treat Pediatric Participants with Secondary Hyperparathyroidism, Stage 3 or 4 Chronic Kidney Disease and Vitamin D Insufficiency. The main questions it aims to answer are:

1. To assess the pharmacokinetics (PK) and Pharmacodynamics (PD) of CTAP101 Capsules
2. To investigate the safety and tolerability of CTAP101 Capsules

Participants will take a daily dosage of CTAP101 Capsules at bedtime for 8 weeks.

Inclusion Criteria:

Each participant must meet the following criteria to be enrolled in Cohort 1 of this study:

1. Be 8 to <18 years of age with a body weight of ≥40 kg.

2. Be diagnosed with stage 3 or 4 CKD at least six months prior to the screening visit (Visit 1) and have an eGFR of ≥15 to <60 mL/min/1.73m2 at screening.

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.

4. Exhibit during the initial or, if necessary, a screening visit after washout:

   1. Plasma iPTH >85 pg/mL;
   2. Serum Ca <9.8 mg/dL;
   3. Serum P ≤5.5 mg/dL; and
   4. Serum 25D <30 ng/mL.

5. If taking calcitriol or other 1α-hydroxylated vitamin D therapy, be willing to forgo treatment with these agents for the duration of the study and complete a 2-week washout period prior to commencing treatment in the study.

6. If receiving ≤2,000 IU/day or 50,000 IU/month (1,250 mcg) vitamin D supplementation (ergocalciferol or cholecalciferol) therapy, must agree to remain on a stable dose during the study.

7. If taking >2,000 IU/day of vitamin D supplementation, must discontinue or decrease the dose to ≤2,000 IU/day, maintain that dose for the duration of the study and complete a 2-week washout period prior to commencing treatment in the study.

8. If taking >1000 mg/day of elemental Ca through Ca-based phosphate binder or antacid therapy, must discontinue or decrease the dose to ≤ 1000 mg/day, maintain that dose for the duration of the study, and complete a 2-week washout period prior to commencing treatment in the study.

9. If taking any bone metabolism therapy that could interfere with study endpoints, must discontinue use of such agent(s) for the duration of the study.

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

11. Willing and able to safely swallow the CTAP101 capsules whole.

12. Female participants of childbearing potential must be neither pregnant nor lactating and must have a negative urine pregnancy test at the first screening visit.

13. All female participants of childbearing potential and male participants 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.

14. Each participant or their legal representative must be able to read, understand and sign the ICF.

Exclusion Criteria:

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

1. Kidney transplant within the 26 weeks preceding screening or kidney transplant rejection within the 26 weeks preceding screening.
2. No history of parathyroidectomy or planned parathyroidectomy.
3. History (prior three months) of serum Ca ≥9.8 mg/dL.
4. Use of calcimimetic or calcifediol therapy within three months prior to consent.
5. Use of bisphosphonate or denosumab therapy within six months prior to consent.
6. Known or suspected hypersensitivity to any of the constituents in CTAP101 Capsules.
7. Known previous or concomitant serious illness or medical condition, such as malignancy, human immunodeficiency virus, significant gastrointestinal or hepatic disease or cardiovascular event or hepatitis, or abnormal ECG or physical condition that in the opinion of the investigator may worsen and/or interfere with participation in the study.
8. History of neurological/psychiatric disorder, including psychotic disorder, or any reason which, in the opinion of the investigator makes adherence to a treatment or FU schedule unlikely.
9. Currently participating in, or has participated in, an interventional/investigational study within 30 days prior to study screening that in the opinion of the investigator and/or sponsor would interfere with the safety, assessments, and results of this study.