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.

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

Study Overview

• Status: Terminated
• Conditions: Chronic Kidney Diseases; Vitamin D Deficiency; Stage 5 Chronic Kidney Disease; Secondary Hyperparathyroidism Due to Renal Causes
• Intervention / Treatment: Drug: Calcifediol Oral Capsule; Drug: Placebo oral capsule

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Peoria, Arizona, United States, 85381
      • AKDHC Medical Research Services
    • Phoenix, Arizona, United States, 85035
      • AKDHC Medical Research Services
    • Phoenix, Arizona, United States, 85027
      • AKDHC Medical Research Services
    • Phoenix, Arizona, United States, 85258
      • AKDHC Medical Research Services
  • California
    • Cypress, California, United States, 90630
      • WCCT Global, Inc.
    • Hacienda Heights, California, United States, 91745
      • Hacienda Dialysis Center
    • La Mesa, California, United States, 91942
      • California Institute of Renal Research CKD/Dialysis & Transplant Division
    • Long Beach, California, United States, 90807
      • Long Beach Quest Dialysis Center
    • Ontario, California, United States, 91762
      • Ontario Dialysis Center
    • San Dimas, California, United States, 91773
      • North America Research Institute, Inc.
    • Sun Valley, California, United States, 91352
      • Laurel Canyon Dialysis, LLC
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver Anschutz Medical Campus
  • Illinois
    • Chicago, Illinois, United States, 60643
      • Research by Design, LLC
    • Evanston, Illinois, United States, 60201
      • Northshore University Health
  • Massachusetts
    • Springfield, Massachusetts, United States, 01107
      • Renal and Transplant Associates of New England
  • Mississippi
    • McComb, Mississippi, United States, 39601
      • Southwest MS Nephrology
  • Texas
    • Houston, Texas, United States, 77099
      • Southwest Houston Research Ltd
    • San Antonio, Texas, United States, 78207
      • Kidney & Hypertension Specialists

Participation Criteria

Eligibility Criteria

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

Description

Each subject must meet the following criteria to be enrolled in 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) 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. Approximately 50% of enrolled subjects will have been receiving calcimimetic therapy.

5. 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.
6. 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.
7. 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.

8. 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):

   1. Plasma iPTH increased by at least 50%;
   2. Plasma iPTH ≥300 pg/mL and <1,200 pg/mL;
   3. Corrected serum calcium <9.8 mg/dL;
   4. Serum total 25-hydroxyvitamin D <50 ng/mL; and,
   5. Serum phosphorus <6.5 mg/dL.
9. 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.
10. 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.
11. Willing and able to comply with study instructions and commit to all clinic visits for the duration of the study.
12. Female subjects of childbearing potential must be neither pregnant nor lactating and must have a negative serum betahuman chorionic gonadotropin (b-hCG) pregnancy test at the first screening visit and at other scheduled times.
13. 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.
14. 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. Scheduled 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-hydroxylated 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CTAP101 Capsules 900mcg/weekly; CTAP101 Oral Capsules/Calcifediol, calcidiol, 25-hydroxyvitamin D3, 900mcg/weekly for 26 weeks	Drug: Calcifediol Oral Capsule; Capsule, weekly; Other Names: CTAP101
Placebo Comparator: Placebo Capsules weekly; Placebo Oral Capsules/weekly for 26 weeks	Drug: Placebo oral capsule; Capsule, weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Response During Efficacy Assessment Period	To evaluate the efficacy of repeated dosing with 900 mcg per week of CTAP101 extended release (ER) Capsules versus placebo in raising mean serum total 25-hydroxyvitamin D (25D) to ≥50 ng/mL and in reducing mean plasma intact parathyroid hormone (iPTH) by at least 30% from pre-treatment baseline.	26 weeks
Total 25-hydroxyvitamin D Response Analysis During Efficacy Period	Summary of participants with mean serum total 25-hydroxyvitamin D ≥50 ng/mL at the end of treatment	26 weeks
Number of Participants With Intact Parathyroid Hormone (iPTH) Response During Efficacy Assessment Period	Summary of participants who experienced a reduction in mean plasma iPTH by greater than 30% from the pre-treatment baseline	26 weeks
Pharmacokinetic (PK) Profile (Cmax) of Serum Calcifediol	To assess Cmax of serum calcifediol after a single dose of 900 mcg at the start of the study (Single Dose PK Period), and a repeat dose of 300 mcg at the end of the study (Repeat Dose PK Period)	0, 4, 8, 12, 16, 20, 24, 30, 36, 42 and 48 hours post-dose (single and repeat dose)
Pharmacokinetic (PK) Profile (Tmax) of Serum Calcifediol	To assess Tmax of serum calcifediol after a single dose of 900 mcg at the start of the study (Single Dose PK Period), and a repeat dose of 300 mcg at the end of the study (Repeat Dose PK Period)	0, 4, 8, 12, 16, 20, 24, 30, 36, 42 and 48 hours post-dose (single and repeat dose)
Pharmacokinetic (PK) Profile (AUC0-t) of Serum Calcifediol	To assess AUC0-t of serum calcifediol after a single dose of 900 mcg at the start of the study (Single Dose PK Period), and a repeat dose of 300 mcg at the end of the study (Repeat Dose PK Period)	0, 4, 8, 12, 16, 20, 24, 30, 36, 42 and 48 hours post-dose (single and repeat dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamic Analysis of 1,25-dihydroxyvitamin D	Effect of CTAP101 on 1,25-dihydroxyvitamin D	26 weeks

Collaborators and Investigators

• Sponsor: OPKO Health, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2018
• Primary Completion (Actual): February 24, 2021
• Study Completion (Actual): February 24, 2021

Study Registration Dates

• First Submitted: July 13, 2018
• First Submitted That Met QC Criteria: July 25, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Nutrition Disorders; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Renal Insufficiency, Chronic; Vitamin D Deficiency; Lipids; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Cholestenes; Cholestanes; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Hydroxycholecalciferols; Cholecalciferol; Calcifediol
• Other Study ID Numbers: CTAP101-CL-2010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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