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

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ClinicalTrials.gov Identifier: NCT03602261
Recruitment Status : Recruiting
First Posted : July 26, 2018
Last Update Posted : June 5, 2019
Sponsor:
Information provided by (Responsible Party):
OPKO Ireland Global Holdings Ltd.

Tracking Information
First Submitted Date  ICMJE July 13, 2018
First Posted Date  ICMJE July 26, 2018
Last Update Posted Date June 5, 2019
Actual Study Start Date  ICMJE July 9, 2018
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 18, 2019)
  • Change of mean plasma intact parathyroid hormone (iPTH) [ Time Frame: 26 weeks ]
    Change of at least 30% from pre-treatment baseline
  • Severity of Treatment-Emergent Adverse Events as assessed by CTCAE version 5.0 [ Time Frame: 32 weeks ]
    Detailed information collected for each TEAE will include: AE number, a description of the event, start date, end date or ongoing as of date, outcome, therapy for event
  • Maximum Plasma Concentration [Cmax] [ Time Frame: 74 weeks ]
    Maximum serum concentration of Calcifediol
  • Increase mean serum total 25-hydroxyvitamin D [ Time Frame: 26 weeks ]
    Increase to ≥30 ng/mL
Original Primary Outcome Measures  ICMJE
 (submitted: July 25, 2018)
  • Reduction of mean plasma intact parathyroid hormone (iPTH) [ Time Frame: 26 weeks ]
    Reduction of at least 30% from pre-treatment baseline
  • Severity of Treatment-Emergent Adverse Events as assessed by CTCAE version 5.0 [ Time Frame: 32 weeks ]
    Detailed information collected for each TEAE will include: AE number, a description of the event, start date, end date or ongoing as of date, outcome, therapy for event
  • Maximum Plasma Concentration [Cmax] [ Time Frame: 74 weeks ]
    Maximum serum concentration of Calcifediol
  • Increase mean serum total 25-hydroxyvitamin D [ Time Frame: 26 weeks ]
    Increase to ≥30 ng/mL
Change History Complete list of historical versions of study NCT03602261 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Efficacy, PK and PD of CTAP101 (Calcifediol) ER Capsules for SHPT in HD Patients VDI
Official Title  ICMJE 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.
Brief Summary Safety, Efficacy, PK and PD of CTAP101 (calcifediol) ER Capsules for SHPT in HD Patients VDI
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Secondary Hyperparathyroidism Due to Renal Causes
  • Chronic Kidney Diseases
  • Vitamin D Deficiency
  • Stage 5 Chronic Kidney Disease
Intervention  ICMJE
  • Drug: Calcifediol Oral Capsule
    Capsule, weekly
    Other Name: CTAP101
  • Drug: Placebo oral capsule
    Capsule, weekly
Study Arms  ICMJE
  • Active Comparator: CTAP101 Capsules 300mcg/weekly
    CTAP101 Oral Capsules/Calcifediol, calcidiol, 25-hydroxyvitamin D3, 300mcg/weekly for 26 weeks
    Intervention: Drug: Calcifediol Oral Capsule
  • Active Comparator: CTAP101 Capsules 600mcg/weekly
    CTAP101 Oral Capsules/Calcifediol, calcidiol, 25-hydroxyvitamin D3, 600mcg/weekly for 26 weeks
    Intervention: Drug: Calcifediol Oral Capsule
  • Active Comparator: CTAP101 Capsules 900mcg/weekly
    CTAP101 Oral Capsules/Calcifediol, calcidiol, 25-hydroxyvitamin D3, 900mcg/weekly for 26 weeks
    Intervention: Drug: Calcifediol Oral Capsule
  • Placebo Comparator: Placebo Capsules weekly
    Placebo Oral Capsules/weekly for 26 weeks
    Intervention: Drug: Placebo oral capsule
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 25, 2018)
256
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 15, 2021
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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) 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. At least 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):

    Cohort 1:

    1. Plasma iPTH increased by at least 50%; and,
    2. Plasma iPTH ≥300 pg/mL and <1,200 pg/mL; or,

    Cohort 2:

    a. Plasma iPTH ≥300 pg/mL and <1,200 pg/mL (approximately half of the subjects will be enrolled in each of these two iPTH strata: ≥300 to <600 and ≥600 to <1,200 pg/mL); and

    Cohorts 1 and 2:

    1. Corrected serum calcium <9.8 mg/dL;
    2. Serum total 25-hydroxyvitamin D <30 ng/mL; and,
    3. 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 beta-human 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.

4.3 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Luis R Paredes 13055754167 lparedes@opko.com
Contact: Evelyn Cheng 13055754129 echeng@opko.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03602261
Other Study ID Numbers  ICMJE CTAP101-CL-2010
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party OPKO Ireland Global Holdings Ltd.
Study Sponsor  ICMJE OPKO Ireland Global Holdings Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account OPKO Ireland Global Holdings Ltd.
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP