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

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

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

Study Overview

• Status: Completed
• Conditions: Vitamin D Insufficiency; CKD Stage 4; CKD Stage 3; Secondary Hyperparathyroidism Due to Renal Causes
• Intervention / Treatment: Drug: Calcifediol Oral Capsule; Drug: Calcifediol Oral Product; Drug: Cholecalciferol; Drug: Paricalcitol Oral Capsule

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Garden Grove, California, United States, 92844
      • National Institute of Clinical Research, Inc.
  • Illinois
    • Chicago, Illinois, United States, 60643
      • Research by Design, LLC
  • Wisconsin
    • West Bend, Wisconsin, United States, 53095
      • Spaulding Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CTAP101; CTAP101/Calcifediol Capsules 60 micrograms (mcg) once daily at bedtime, except on Days 1 and 29 when dosing will occur in the morning before breakfast	Drug: Calcifediol Oral Capsule; Capsule, daily; Other Names: CTAP101
Experimental: Immediate-release (IR) calcifediol; Immediate-release (IR) calcifediol/266 micrograms (mcg) capsule before breakfast on the mornings of Day 1 and Day 29	Drug: Calcifediol Oral Product; Capsule, once a month
Experimental: Cholecalciferol; Cholecalciferol/Capsules 300,000 International Units (IU) (high-dose) before breakfast on the mornings of Day 1 and Day 29	Drug: Cholecalciferol; Capsule, once a month
Active Comparator: Paricalcitol; Paricalcitol/Capsules 1 mcg plus cholecalciferol capsules 800 IU (low-dose) once daily in the morning before breakfast, except on Days 1 and29 when dosing will occur before breakfast	Drug: Cholecalciferol; Capsule, once a month; Drug: Paricalcitol Oral Capsule; Capsule, daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.	This study is descriptive and no primary or secondary efficacy endpoints are defined.	5 months

Collaborators and Investigators

• Sponsor: OPKO Health, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2018
• Primary Completion (Actual): April 24, 2020
• Study Completion (Actual): April 24, 2020

Study Registration Dates

• First Submitted: June 28, 2018
• First Submitted That Met QC Criteria: July 16, 2018
• First Posted (Actual): July 17, 2018

Study Record Updates

• Last Update Posted (Estimate): December 9, 2022
• Last Update Submitted That Met QC Criteria: November 14, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urologic Diseases; Endocrine System Diseases; Renal Insufficiency; Parathyroid Diseases; Neoplastic Processes; Kidney Diseases; Renal Insufficiency, Chronic; Hyperparathyroidism; Neoplasm Metastasis; Hyperparathyroidism, Secondary; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Calcifediol
• Other Study ID Numbers: CTAP101-CL-4001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No