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

Stopped early · Phase 1 · Has a placebo group

Conditions studied: Hypoparathyroidism

In brief

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.

Key facts

Study ID

NCT04209179

Run by

Chugai Pharmaceutical

People needed

5

Starts

2020-07-23

Expected to finish

2021-05-25

Last updated by the study team

2021-06-11

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.
• Adult males or females ≥18 years of age
• History of hypoparathyroidism for more than 1-year post initial diagnosis
• PTH level is inappropriately low
• Dose of thyroid replacement therapy must have been stable for ≥3 months prior to first dose if receiving thyroid replacement therapy
• Receiving treatment with active vitamin D therapy (calcitriol ≥0.25 μg/day or alfacalcidol ≥0.5 μg/day)
• Receiving Oral calcium treatment (≥1000 mg/day)
• No significant changes in the diet from 4 weeks prior to Screening and for the duration of the study.
• 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.
• On Day 1, fasting albumin-corrected serum calcium level between 7.5 and 9.0 mg/dL
• Serum magnesium level ≥ lower limit of normal and ≤ 1.2 x laboratory upper limit of normal
• Serum 25[OH] vitamin D level within the laboratory normal range
• Estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2
• Women of childbearing potential must have a negative highly sensitive urine or serum pregnancy test result
• 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.
• For men: agreement to remain abstinent or use contraceptive measures. Men must refrain from donating sperm during this same period.
• Ability to comply with the study protocol, in the investigator's judgment.
• For Canadian sites only: Ferritin, as assessed by the local laboratory at screening, must be ≥ the lower limit of normal (LLN).

You may not qualify if…

• Pregnant or breastfeeding or intending to become pregnant during the study or within 28 days after the last dose of PCO371
• Known or suspected history of hypoparathyroidism resulting from an activating mutation in the Ca-sensing receptor gene or impaired responsiveness to PTH (pseudohypoparathyroidism)
• Clinically significant hypomagnesemia. Adequately treated hypomagnesemia is permitted
• Any disease that might affect calcium metabolism or calcium-phosphate homeostasis other than hypoparathyroidism
• History of a major bone fracture within 3 months prior to Screening
• Any history of clinically significant bleeding disorder or clinically significant abnormal clotting times
• History of thyroid cancer unless documented to be disease free for ≥1 year
• 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
• Dependence on monthly or more frequent parenteral calcium infusions to maintain calcium homeostasis
• Disease processes that may adversely affect gastrointestinal absorption
• 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.
• 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.
• 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).
• Use of loop or thiazide diuretics within 14 days prior to first dose of IMP
• 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
• Use of proton pump inhibitors or H2 blockers within 48 hours prior to the first dose of IMP and antacids within 4 hours prior to the first dose of IMP.
• History of radiotherapy to the skeleton within 5 years
• Presence of open epiphyses at the distal radius and ulna as well as carpals, metacarpals, phalanges, and pelvis
• ALT, AST, or ALP > 2.5 × ULN at Screening
• Patients with documented active HBV, active HCV infection or any other known active virus infection considered to be clinically relevant by the investigator.
• Evidence of active alcohol, drug, or other substance abuse or addiction
• History of a seizure that is unrelated to hypocalcemia within 6 months prior to Screening
• Insulin dependent diabetes mellitus or poorly controlled Type II diabetes mellitus (defined as hemoglobin A1c [HbA1c] >8%)
• Chronic/severe cardiac disease
• Active gout or history of active gout within 6 months prior to first dose of study medication

Where it is running

• The Lundquist Institute — Torrance, California, United States
• University of Chicago — Chicago, Illinois, United States
• Indiana University School of Medicine — Indianapolis, Indiana, United States
• University of Kentucky — Lexington, Kentucky, United States
• Massachusetts General Hospital — Boston, Massachusetts, United States
• Mayo Clinic — Rochester, Minnesota, United States
• Ohio State University Wexner Medical Center — Columbus, Ohio, United States
• Thomas Jefferson University — Philadelphia, Pennsylvania, United States
• Endocrinologie et néphrologie Centre de recherche du CHU de Québec — Québec, CAN, Canada
• McMaster University Bone Research & Education Centre — Oakville, Ontario, Canada
• Semmelweis Egyetem, Általános Orvostudományi Kar, Belgyógyászati és Onkológiai Klinika — Budapest, HU, Hungary

Full record on ClinicalTrials.gov

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