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A Clinical Study Investigating the Safety, Tolerability, PK and PD of PCO371 in Patients With Hypoparathyroidism

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04209179
Recruitment Status : Recruiting
First Posted : December 24, 2019
Last Update Posted : May 11, 2020
Sponsor:
Information provided by (Responsible Party):
Chugai Pharmaceutical

Brief Summary:

This is a multi-center, placebo-controlled, randomized, double-blind, multiple-ascending dose study in patients with hypoparathyroidism.

The total duration of study medication treatment will be 13 weeks and includes a Fixed-Dose Treatment period and a Dose Titration Treatment period. The Fixed-Dose Treatment period consists of multiple daily dosing at a fixed dose level. Once patients have completed the Fixed-Dose Treatment period, patients will enter the Dose Titration Treatment period where PCO371 (or placebo), oral calcium and oral active vitamin D can each be titrated according to the patient's albumin-corrected serum calcium level.


Condition or disease Intervention/treatment Phase
Hypoparathyroidism Drug: PCO371 Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Multiple Ascending Oral Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PCO371 in Patients With Hypoparathyroidism
Estimated Study Start Date : May 31, 2020
Estimated Primary Completion Date : May 31, 2021
Estimated Study Completion Date : May 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PCO371 Low Dose and Low administration frequency
PCO371 low dose and low administration frequency by oral administration for the first period ( Fixed-Dose treatment period). PCO371 will be titrated in the following period (Dose Titration Treatment period).
Drug: PCO371
PCO371 capsule

Experimental: PCO371 High Dose and Low administration frequency
PCO371 high dose and low administration frequency by oral administration for the first period ( Fixed-Dose treatment period). PCO371 will be titrated in the following period (Dose Titration Treatment period).
Drug: PCO371
PCO371 capsule

Experimental: PCO371 High Dose and High administration frequency
PCO371 high dose and high administration frequency by oral administration for the first period ( Fixed-Dose treatment period). PCO371 will be titrated in the following period (Dose Titration Treatment period).
Drug: PCO371
PCO371 capsule

Placebo Comparator: Placebo
Placebo by oral administration.
Drug: Placebo
Placebo capsule




Primary Outcome Measures :
  1. Treatment-emergent adverse events [ Time Frame: 13 weeks ]
    Treatment-emergent adverse events (TEAEs) will be assessed including the number and rate of TEAEs.

  2. Selected adverse events [ Time Frame: 13 weeks ]
    Hypercalcemia and hypocalcemia will be assessed including the number and rate of these.

  3. Clinically significant change in the safety parameters; vital signs [ Time Frame: 13 weeks ]
    Abnormal change in vital signs.

  4. Clinically significant change in the safety parameters; body weight [ Time Frame: 13 weeks ]
    Abnormal change in body weight.

  5. Clinically significant change in the safety parameters; physical examination findings [ Time Frame: 13 weeks ]
    Abnormal change in physical examination findings.

  6. Clinically significant change in the safety parameters; laboratory test value [ Time Frame: 13 weeks ]
    Abnormal change in laboratory test value including hematology, biochemistry, coagulation, urinalysis.

  7. Clinically significant change in the safety parameters; electrocardiogram results [ Time Frame: 13 weeks ]
    Abnormal change in electrocardiogram results including PQ (PR), RR, QRS, QT, pulse, QTcB, QTcF and ECG abnormalities.


Secondary Outcome Measures :
  1. Pharmacokinetic data of PCO371; Plasma concentrations of PCO371 [ Time Frame: 13 weeks ]
    Plasma concentrations versus time data

  2. Pharmacokinetic data of PCO371; AUC0-last [ Time Frame: 13 weeks ]
    AUC0-last of PCO371

  3. Pharmacokinetic data of PCO371; Cmax of PCO371 [ Time Frame: 13 weeks ]
    Cmax of PCO371

  4. Pharmacokinetic data of PCO371; Tmax of PCO371 [ Time Frame: 13 weeks ]
    Tmax of PCO371

  5. Pharmacokinetic data of PCO371; T1/2 of PCO371 [ Time Frame: 13 weeks ]
    T1/2 of PCO371

  6. Pharmacodynamic data in serum or plasma [ Time Frame: 13 weeks ]
    Time profile of serum/plasma concentrations in albumin corrected total calcium (Ca), 25 hydroxy vitamin D, 1,25-dihydroxy vitamin D, phosphate, magnesium, and cAMP

  7. Pharmacodynamic data in urine [ Time Frame: 13 weeks ]
    Urinary excretion of Ca, phosphate, magnesium, protein, sodium, potassium, chloride, and cAMP (via 24-hour urine collection)

  8. Pharmacodynamic data; nephrogenous cAMP concentration [ Time Frame: 13 weeks ]
    Time profile of nephrogenous cAMP concentration

  9. Pharmacodynamic data; bone turnover markers in serum or plasma [ Time Frame: 13 weeks ]
    Time profile of serum/plasma concentrations in bone turnover markers (i.e. bone-specific alkaline phosphatase, type 1 pro-collagen amino-terminal peptide, C-terminal telopeptide of type 1 collagen, and osteocalcin)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Able and willing to provide written informed consent, to use the device for PRO and electronic diary and to comply with the requirements of the protocol.
  2. Adult males or females ≥18 years of age
  3. History of hypoparathyroidism for more than 1-year post initial diagnosis
  4. PTH level is inappropriately low
  5. Dose of thyroid replacement therapy must have been stable for ≥3 months prior to first dose if receiving thyroid replacement therapy
  6. Receiving treatment with active vitamin D therapy (calcitriol ≥0.25 μg/day or alfacalcidol ≥0.5 μg/day)
  7. Receiving Oral calcium treatment (≥1000 mg/day)
  8. No significant changes in the diet from 4 weeks prior to Screening and for the duration of the study.
  9. Fasting albumin-corrected serum calcium concentration between 8.0 and 9.0 mg/dL at 2 consecutive visits during the Run-In period, and no more than 25% change in daily doses of oral Ca and active vitamin D between the 2 consecutive visits during the Run-In period.
  10. On Day 1, fasting albumin-corrected serum calcium level between 7.5 and 9.0 mg/dL
  11. Serum magnesium level ≥ lower limit of normal and ≤ 1.2 x laboratory upper limit of normal
  12. Serum 25[OH] vitamin D level within the laboratory normal range
  13. Estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2
  14. Women of childbearing potential must have a negative highly sensitive urine or serum pregnancy test result
  15. For women of childbearing potential: agreement to use a highly effective contraceptive method during the treatment period and for 28 days after the last dose of study drug. Hormonal contraceptive methods must be supplemented by a barrier method (preferably male condom) and agreement to refrain from egg donation during the treatment period and for 28 days after the last dose of study drug.
  16. For men: agreement to remain abstinent or use contraceptive measures. Men must refrain from donating sperm during this same period.
  17. Ability to comply with the study protocol, in the investigator's judgment.

Exclusion Criteria:

  1. Pregnant or breastfeeding or intending to become pregnant during the study or within 28 days after the last dose of PCO371
  2. Known or suspected history of hypoparathyroidism resulting from an activating mutation in the Ca-sensing receptor gene or impaired responsiveness to PTH (pseudohypoparathyroidism)
  3. Clinically significant hypomagnesemia. Adequately treated hypomagnesemia is permitted
  4. Any disease that might affect calcium metabolism or calcium-phosphate homeostasis other than hypoparathyroidism
  5. History of a major bone fracture within 3 months prior to Screening
  6. Any history of clinically significant bleeding disorder or clinically significant abnormal clotting times
  7. History of thyroid cancer unless documented to be disease free for ≥1 year
  8. History of any other cancer in the past 3 years from Screening with the exception of thyroid cancer , completely removed nonmelanoma skin cancer, basal cell skin carcinoma, and cancer in situ of the cervix
  9. Dependence on monthly or more frequent parenteral calcium infusions to maintain calcium homeostasis
  10. Disease processes that may adversely affect gastrointestinal absorption
  11. Use of oral bisphosphonates within 6 months of Screening and/or intravenous bisphosphonate preparations within 12 months of Screening. Any use of zoledronic acid prior to Screening.
  12. Use of other drugs known to influence calcium and bone metabolism such as calcitonin, fluoride tablets or cinacalcet hydrochloride within 4 weeks prior to Screening.
  13. Patients who have taken inducers of CYP3A4, Pgp,or BCRP within 1 month before IMP administration or taken inhibitors of CYP3A4, P-gp, or BCRP within 2 weeks before IMP administration (or either 6 times the t1/2 of the drugs mentioned above, whichever is longer).
  14. Use of loop or thiazide diuretics within 14 days prior to first dose of IMP
  15. Use of anti-coagulants, anti-platelet medications, and aspirin within 2 weeks (or within 6 times the t1/2 of the drug mentioned above, whichever is longer) prior to IMP administration
  16. History of radiotherapy to the skeleton within 5 years
  17. Presence of open epiphyses at the distal radius and ulna as well as carpals, metacarpals, phalanges, and pelvis
  18. ALT, AST, or ALP > 2.5 × ULN at Screening
  19. Patients with documented active HBV, active HCV infection or any other known active virus infection considered to be clinically relevant by the investigator.
  20. Evidence of active alcohol, drug, or other substance abuse or addiction
  21. History of a seizure that is unrelated to hypocalcemia within 6 months prior to Screening
  22. Insulin dependent diabetes mellitus or poorly controlled Type II diabetes mellitus (defined as hemoglobin A1c [HbA1c] >8%)
  23. Chronic/severe cardiac disease
  24. Active gout or history of active gout within 6 months prior to first dose of study medication
  25. History of clinically significant cognitive deficit that would, at the discretion of the investigator, interfere with a patient's ability to participate in the trial.
  26. Any disease or condition that, in the opinion of the investigator, has a high probability of precluding the patient from completing the study or where the patient could not or would not appropriately comply with study requirements
  27. Participation in any clinical trials or has taken any IMP (including placebo) either within 2 months or 5 times the t1/2 of the IMP, whichever is longer, prior to first dose of IMP for this study
  28. Previous treatment with PTH-like drugs, including PTH(1-84), PTH(1-34) or other N-terminal fragments or analogs of PTH or PTH-related proteins within 2 months or 5 times the t1/2 of the treatment (whichever is longer) prior to Screening.
  29. Patients with hypersensitivity to PCO371 or to any component of this drug product

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04209179


Contacts
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Contact: Clinical trials information only use Email clinical-trials@chugai-pharm.co.jp

Locations
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United States, Ohio
Ohio State University Wexner Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Amber Anaya         
Contact    (614) 688-6257    amber.anaya@osumc.edu   
Sponsors and Collaborators
Chugai Pharmaceutical
Investigators
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Study Director: Sponsor Chugai Pharmaceutical Co. Ltd clinical-trials@chugai-pharm.co.jp
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Responsible Party: Chugai Pharmaceutical
ClinicalTrials.gov Identifier: NCT04209179    
Other Study ID Numbers: PCO104UG
First Posted: December 24, 2019    Key Record Dates
Last Update Posted: May 11, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). For further details on Chugai's Data Sharing Policy and how to request access to related clinical study documents, see here (www.chugai-pharm.co.jp/english/profile/rd/ctds_request.html).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hypoparathyroidism
Parathyroid Diseases
Endocrine System Diseases