HypoparathyroidismPhase 1NCT04209179
A Clinical Study Investigating the Safety, Tolerability, PK and PD of PCO371 in Patients With Hypoparathyroidism
A Phase 1 study testing PCO371 in people with Hypoparathyroidism, run by Chugai Pharmaceutical at 11 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypoparathyroidism
- What is being tested?
- PCO371
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 11 sitesin 3 countries
- Study dates
- 23 Jul 2020to 25 May 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 18Show fewer
- 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).
Who cannot join
- 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
Show all 30Show fewer
- 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
- 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.
- 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
- 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
- Previous treatment with PTH-like drugs, including PTH(1-84), PTH(1-34) or other Nterminal 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.
- Patients with hypersensitivity to PCO371 or to any component of this drug product
Trial locations and contacts
11 sites in 3 countries.
11 sites in 3 countries
United States8 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of Chicago
Chicago, Illinois, 60637
Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
Indiana University School of Medicine
Indianapolis, Indiana, 46202
University of Kentucky
Lexington, Kentucky, 40536
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Mayo Clinic
Rochester, Minnesota, 55905
The Lundquist Institute
Torrance, California, 90502
Canada2 sites
McMaster University Bone Research & Education Centre
Oakville, Ontario, L6M 1M1
Endocrinologie et néphrologie Centre de recherche du CHU de Québec
Québec, CAN, G1V 4G2
Hungary1 site
Semmelweis Egyetem, Általános Orvostudományi Kar, Belgyógyászati és Onkológiai Klinika
Budapest, HU, 1083
About this study
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
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.
- Conditions
- Hypoparathyroidism
- Being tested
- PCO371, Placebo
- Medical subject headings
- Hypoparathyroidism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PCO371Drug
PCO371 capsule
PlaceboDrug
Placebo capsule
| Study group | Role | What they receive |
|---|---|---|
| PCO371 Low Dose and Low administration frequency | Experimental | 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). Receives: Drug: PCO371 |
| PCO371 High Dose and Low administration frequency | Experimental | 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). Receives: Drug: PCO371 |
| PCO371 High Dose and High administration frequency | Experimental | 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). Receives: Drug: PCO371 |
| Placebo | Placebo comparator | Placebo by oral administration. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-emergent adverse events
Treatment-emergent adverse events (TEAEs) will be assessed including the number and rate of TEAEs.
Measured: 13 weeks
Selected adverse events
Hypercalcemia and hypocalcemia will be assessed including the number and rate of these.
Measured: 13 weeks
Clinically significant change in the safety parameters; vital signs
Abnormal change in vital signs.
Measured: 13 weeks
Clinically significant change in the safety parameters; body weight
Abnormal change in body weight.
Measured: 13 weeks
Clinically significant change in the safety parameters; physical examination findings
Abnormal change in physical examination findings.
Measured: 13 weeks
Clinically significant change in the safety parameters; laboratory test value
Abnormal change in laboratory test value including hematology, biochemistry, coagulation, urinalysis.
Measured: 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.
Measured: 13 weeks
Secondary outcomes (9)
Pharmacokinetic data of PCO371; Plasma concentrations of PCO371
Plasma concentrations versus time data
Measured: 13 weeks
Pharmacokinetic data of PCO371; AUC0-last
AUC0-last of PCO371
Measured: 13 weeks
Pharmacokinetic data of PCO371; Cmax of PCO371
Cmax of PCO371
Measured: 13 weeks
Pharmacokinetic data of PCO371; Tmax of PCO371
Tmax of PCO371
Measured: 13 weeks
Pharmacokinetic data of PCO371; T1/2 of PCO371
T1/2 of PCO371
Measured: 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
Measured: 13 weeks
Pharmacodynamic data in urine
Urinary excretion of Ca, phosphate, magnesium, protein, sodium, potassium, chloride, and cAMP (via 24-hour urine collection)
Measured: 13 weeks
Pharmacodynamic data; nephrogenous cAMP concentration
Time profile of nephrogenous cAMP concentration
Measured: 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)
Measured: 13 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2019
- Study start23 Jul 2020
- Primary completion28 Dec 2020
- Study completion25 May 2021
Why it stopped: Terminated on the basis of the currently uncertain risk-benefit balance for the patients, and the strategic position of the development program
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypoparathyroidismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chugai Pharmaceutical
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sponsor Chugai Pharmaceutical Co. Ltd, Study director, clinical-trials@chugai-pharm.co.jp
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04209179
- Sponsor's protocol ID
- PCO104UG
- Status last verified
- Jun 2021
- First submitted
- 28 Nov 2019
- Last updated
- 11 Jun 2021
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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).
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04209179
- Acronym / sponsor ID
- PCO104UG
- Conditions
- Hypoparathyroidism
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated on the basis of the currently uncertain risk-benefit balance for the patients, and the strategic position of the development program
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Chugai PharmaceuticalIndustry (pharma, biotech, devices)
- Study start
- 23 Jul 2020 (actual)
- Primary completion
- 28 Dec 2020 (actual)
- Study completion
- 25 May 2021 (actual)
- First posted
- 24 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| PCO371 Low Dose and Low administration frequency | Experimental | Drug: PCO371PCO371 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). |
| PCO371 High Dose and Low administration frequency | Experimental | Drug: PCO371PCO371 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). |
| PCO371 High Dose and High administration frequency | Experimental | Drug: PCO371PCO371 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). |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo by oral administration. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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
Key exclusion criteria (30 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PCO371PCO371 capsule | Drug | PCO371 High Dose and High administration frequency, PCO371 High Dose and Low administration frequency, PCO371 Low Dose and Low administration frequency |
| PlaceboPlacebo capsule | Drug | Placebo |
Primary outcome
Treatment-emergent adverse events
Time frame: 13 weeks
Treatment-emergent adverse events (TEAEs) will be assessed including the number and rate of TEAEs.
Selected adverse events
Time frame: 13 weeks
Hypercalcemia and hypocalcemia will be assessed including the number and rate of these.
Clinically significant change in the safety parameters; vital signs
Time frame: 13 weeks
Abnormal change in vital signs.
Clinically significant change in the safety parameters; body weight
Time frame: 13 weeks
Abnormal change in body weight.
Clinically significant change in the safety parameters; physical examination findings
Time frame: 13 weeks
Abnormal change in physical examination findings.
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.
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.
9 secondary outcomes
Pharmacokinetic data of PCO371; Plasma concentrations of PCO371
Time frame: 13 weeks
Pharmacokinetic data of PCO371; AUC0-last
Time frame: 13 weeks
Pharmacokinetic data of PCO371; Cmax of PCO371
Time frame: 13 weeks
Pharmacokinetic data of PCO371; Tmax of PCO371
Time frame: 13 weeks
Pharmacokinetic data of PCO371; T1/2 of PCO371
Time frame: 13 weeks
Pharmacodynamic data in serum or plasma
Time frame: 13 weeks
Pharmacodynamic data in urine
Time frame: 13 weeks
Pharmacodynamic data; nephrogenous cAMP concentration
Time frame: 13 weeks
Pharmacodynamic data; bone turnover markers in serum or plasma
Time frame: 13 weeks
Results and safety
The study was stopped early (reason given: Terminated on the basis of the currently uncertain risk-benefit balance for the patients, and the strategic position of the development program). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2021.
- Individual participant dataSharing planned: Yes. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sponsor Chugai Pharmaceutical Co. Ltd study director
clinical-trials@chugai-pharm.co.jp
11 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PCO371 in people with Hypoparathyroidism, run by Chugai Pharmaceutical at 11 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Canada, Hungary. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Terminated on the basis of the currently uncertain risk-benefit balance for the patients, and the strategic position of the development program). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment-emergent adverse events (time frame: 13 weeks). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2021.