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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
5
PCO371 capsule
Placebo capsule
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
...and 1 more locations
Treatment-emergent adverse events
Treatment-emergent adverse events (TEAEs) will be assessed including the number and rate of TEAEs.
Time frame: 13 weeks
Selected adverse events
Hypercalcemia and hypocalcemia will be assessed including the number and rate of these.
Time frame: 13 weeks
Clinically significant change in the safety parameters; vital signs
Abnormal change in vital signs.
Time frame: 13 weeks
Clinically significant change in the safety parameters; body weight
Abnormal change in body weight.
Time frame: 13 weeks
Clinically significant change in the safety parameters; physical examination findings
Abnormal change in physical examination findings.
Time frame: 13 weeks
Clinically significant change in the safety parameters; laboratory test value
Abnormal change in laboratory test value including hematology, biochemistry, coagulation, urinalysis.
Time frame: 13 weeks
Clinically significant change in the safety parameters; electrocardiogram results
Abnormal change in electrocardiogram results including PQ (PR), RR, QRS, QT, pulse, QTcB, QTcF and ECG abnormalities.
Time frame: 13 weeks
Pharmacokinetic data of PCO371; Plasma concentrations of PCO371
Plasma concentrations versus time data
Time frame: 13 weeks
Pharmacokinetic data of PCO371; AUC0-last
AUC0-last of PCO371
Time frame: 13 weeks
Pharmacokinetic data of PCO371; Cmax of PCO371
Cmax of PCO371
Time frame: 13 weeks
Pharmacokinetic data of PCO371; Tmax of PCO371
Tmax of PCO371
Time frame: 13 weeks
Pharmacokinetic data of PCO371; T1/2 of PCO371
T1/2 of PCO371
Time frame: 13 weeks
Pharmacodynamic data in serum or plasma
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
Time frame: 13 weeks
Pharmacodynamic data in urine
Urinary excretion of Ca, phosphate, magnesium, protein, sodium, potassium, chloride, and cAMP (via 24-hour urine collection)
Time frame: 13 weeks
Pharmacodynamic data; nephrogenous cAMP concentration
Time profile of nephrogenous cAMP concentration
Time frame: 13 weeks
Pharmacodynamic data; bone turnover markers in serum or plasma
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)
Time frame: 13 weeks
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