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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

Primary Purpose

Secondary Hyperparathyroidism Due to Renal Causes, Vitamin D Insufficiency, CKD Stage 3

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Calcifediol Oral Capsule
Calcifediol Oral Product
Cholecalciferol
Paricalcitol Oral Capsule
Sponsored by
OPKO Health, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Secondary Hyperparathyroidism Due to Renal Causes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • National Institute of Clinical Research, Inc.
  • Research by Design, LLC
  • Spaulding Clinical Research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Experimental

Active Comparator

Arm Label

CTAP101

Immediate-release (IR) calcifediol

Cholecalciferol

Paricalcitol

Arm Description

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

Immediate-release (IR) calcifediol/266 micrograms (mcg) capsule before breakfast on the mornings of Day 1 and Day 29

Cholecalciferol/Capsules 300,000 International Units (IU) (high-dose) before breakfast on the mornings of Day 1 and Day 29

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
June 28, 2018
Last Updated
November 14, 2022
Sponsor
OPKO Health, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03588884
Brief Title
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
Official Title
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 Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
June 8, 2018 (Actual)
Primary Completion Date
April 24, 2020 (Actual)
Study Completion Date
April 24, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
OPKO Health, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Secondary Hyperparathyroidism Due to Renal Causes, Vitamin D Insufficiency, CKD Stage 3, CKD Stage 4

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
69 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CTAP101
Arm Type
Active Comparator
Arm Description
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
Arm Title
Immediate-release (IR) calcifediol
Arm Type
Experimental
Arm Description
Immediate-release (IR) calcifediol/266 micrograms (mcg) capsule before breakfast on the mornings of Day 1 and Day 29
Arm Title
Cholecalciferol
Arm Type
Experimental
Arm Description
Cholecalciferol/Capsules 300,000 International Units (IU) (high-dose) before breakfast on the mornings of Day 1 and Day 29
Arm Title
Paricalcitol
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Calcifediol Oral Capsule
Other Intervention Name(s)
CTAP101
Intervention Description
Capsule, daily
Intervention Type
Drug
Intervention Name(s)
Calcifediol Oral Product
Intervention Description
Capsule, once a month
Intervention Type
Drug
Intervention Name(s)
Cholecalciferol
Intervention Description
Capsule, once a month
Intervention Type
Drug
Intervention Name(s)
Paricalcitol Oral Capsule
Intervention Description
Capsule, daily
Primary Outcome Measure Information:
Title
Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
Description
This study is descriptive and no primary or secondary efficacy endpoints are defined.
Time Frame
5 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Be at least 18 years of age. 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). 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: Serum albumin ≤ 3.0 (grams per deciliter (g/dL); Serum transaminase (alanine transaminase, glutamic pyruvic transaminase, aspartate aminotransferase or glutamic oxaloacetic transaminase) > 2.5 times the upper limit of normal at screening; and, Urinary albumin excretion ≤3000 microgram per milligram (μg/mg) creatinine. Exhibit during the initial screening visit: 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 Plasma iPTH ≥100 pg/mL and <500 pg/mL if not receiving calcitriol or other 1α- hydroxylated vitamin D analog; and, Serum total 25-hydroxyvitamin D <30 nanogram per milliliter (ng/mL). 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. Exhibit after the 4-week washout period (if required): Plasma iPTH ≥100 pg/mL and <500 pg/mL; Corrected serum calcium <9.8 mg/dL; (corrected for serum albumin) Serum total 25-hydroxyvitamin D <30 nanogram per milliliter (ng/mL); and, Serum phosphorus <5.5 milligram per deciliter (mg/dL). 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. Willing and able to comply with study instructions and commit to all clinic visits for the duration of the study. Female subjects of childbearing potential must be neither pregnant nor lactating and must have negative blood pregnancy tests at the first screening visit. 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. 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: History of or planned kidney transplant or parathyroidectomy 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. Need for phosphate binders to maintain the serum phosphate < 5.5 mg/dL or use of phosphate binders within 4 weeks prior to screening Use of calcimimetic therapy (cinacalcet or etelcalcetide) within 12 weeks of screening. Receipt of bisphosphonate therapy or other bone modifying treatment within 6 months prior to enrollment. 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. 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. Known or suspected hypersensitivity to any of the constituents of the study drugs. Currently participating in, or has participated in, an interventional/investigational study within 30 days prior to study screening.
Facility Information:
Facility Name
National Institute of Clinical Research, Inc.
City
Garden Grove
State/Province
California
ZIP/Postal Code
92844
Country
United States
Facility Name
Research by Design, LLC
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60643
Country
United States
Facility Name
Spaulding Clinical Research
City
West Bend
State/Province
Wisconsin
ZIP/Postal Code
53095
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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