Autosomal Dominant Hypocalcemia (ADH)Phase 2NCT02204579
A Study to Determine the Effects of NPSP795 on the Calcium-sensing Receptor in Subjects With Autosomal Dominant Hypocalcemia as Measured by PTH Levels and Blood Calcium Concentrations
A Phase 2 study testing NPSP795 in people with Autosomal Dominant Hypocalcemia (ADH), run by Shire at 1 site in United States.
Trial summary
This is an open-label study looking at the effects of NPSP795 (a selective calcium receptor antagonist) on activating mutations of the Calcium-sensing receptor in patients with Autosomal Dominant Hypocalcemia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Autosomal Dominant Hypocalcemia (ADH)
- What is being tested?
- NPSP795
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jul 2014to 4 May 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Subjects with a heterozygous activating mutation of the CaSR gene (ADH); if not previously confirmed, genetic testing will be performed at the screening visit
- At least 18 years of age
- Body mass index (BMI) ≥ 18.5 to < 39 kg/m2
Who cannot join
- Diseases or conditions that might compromise any major body system or interfere with the pharmacokinetics of NPSP795
- History of treatment with PTH 1-84 or 1-34 within the previous 6 months
- History of hypocalcemia requiring frequent IV calcium infusions
- History of hypocalcemic seizure within the past 3 months
- Blood 25-hydroxy vitamin D level < 25 ng/mL. If subjects have a blood 25-hydroxy vitamin D level < 25 ng/mL at the outpatient screening visit, they will be prescribed vitamin D replacement. Once the 25-hydroxy vitamin D level is > 25 ng/mL, the subject will be eligible to continue on to the treatment phase of the study
- Estimated glomerular filtration rate (GFR) < 25 mL/minute, and/or abnormal hepatic, hematologic, and/or clotting function
Show all 9Show fewer
- 12 lead resting electrocardiogram (ECG) with clinically significant abnormalities
- Concomitant medications with the potential to interfere with NPSP795 metabolism
- History of thyroid or parathyroid surgery
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Health (NIH)
Bethesda, Maryland, 20892-1103
About this study
Official title: Open-label Dose Escalation Study Evaluating the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Intravenous NPSP795 in Autosomal Dominant Hypocalcemia Due to Mutations in the Calcium-sensing Receptor Gene: A Drug Repurposing Study
This is an open-label study looking at the effects of NPSP795 (a selective calcium receptor antagonist) on activating mutations of the Calcium-sensing receptor in patients with Autosomal Dominant Hypocalcemia. Patients with ADH have low blood calcium levels and an inappropriately increased renal calcium excretion, decreased renal phosphate excretion, and hyperphosphatemia. PTH and blood calcium levels will be tested during and after the IV infusion of NPSP795. Concentrations of NPSP795 and length of time of IV infusion will vary depending on measured levels of ionized calcium.
- Conditions
- Autosomal Dominant Hypocalcemia (ADH)
- Being tested
- NPSP795
- Keywords
- Autosomal Dominant Hypocalcemia, Hypocalcemia, ADH, Hypoparathyroidism
- Medical subject headings
- Hypercalciuric Hypocalcemia, Familial, Hypocalcemia, Hypoparathyroidism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NPSP795Drug
| Study group | Role | What they receive |
|---|---|---|
| NPSP795 | Experimental | intravenous Receives: Drug: NPSP795 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Measured: From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)
Number of Participants With Clinically Significant Vital Signs and Electrocardiogram (ECG) Abnormalities
Measured: From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)
Number of Participants With Potentially Clinically Important Laboratory Abnormalities
Measured: From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)
Number of Participants With Clinically Significant Abnormalities Related to Physical Examination
Measured: From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)
Change From Baseline in Ionised Calcium
Measured: 10 Minute (min) Infusion Time: within 5 min pre-dose; & post-dose 15, 30, 45, 60, 75, 90, 105 min, and 2, 2.5, 3, 3.5, & 4 hour (hr) 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 15, 30, 45, 60, 75, 90, 105 min, & 2, 2.5, 3, 3.5, 4, 5, and 8 hr
Change From Baseline in Serum Calcium
Measured: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 1, 2, 3, 4, 8 12 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 1, 2, 3, 4, 8 12 hr.
Change From Baseline in Urinary Calcium
Measured: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 1, 2, 3, 4, 8 12 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 1, 2, 3, 4, 8 12 hr.
Change From Baseline in Serum Parathyroid Hormone (PTH)
Measured: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 5, 10, 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr
Secondary outcomes (5)
Area Under the Plasma Concentration Versus Time Curve (AUC[0-t]) of NPSP795
Measured: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 5, 10, 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr
Area Under the Concentration Time Curve Extrapolated to Infinity (AUC0-infinity) of NPSP795
Measured: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 5, 10, 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr
Maximum Observed Drug Concentration (Cmax) of NPSP795 in Plasma
Measured: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 5, 10, 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr
Elimination Half-life (t1/2) of NPSP795 in Plasma
Measured: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 5, 10, 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr
Change From Baseline in Fractional Excretion of Calcium (FECa)
Measured: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 1, 2, 3, 4, 8, 12 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 1, 2, 3, 4, 8, 12 hr.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2014 (estimated)
- Study start18 Jul 2014
- Primary completion4 May 2015
- Study completion4 May 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Autosomal Dominant Hypocalcemia (ADH)Studies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02204579
- Sponsor's protocol ID
- CAL-C13-001
- Status last verified
- Aug 2021
- First submitted
- 28 Jul 2014
- Last updated
- 9 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label Dose Escalation Study Evaluating the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Intravenous NPSP795 in Autosomal Dominant Hypocalcemia Due to Mutations in the Calcium-sensing Receptor Gene: A Drug Repurposing Study
- ClinicalTrials.gov ID
- NCT02204579
- Acronym / sponsor ID
- CAL-C13-001
- Conditions
- Autosomal Dominant Hypocalcemia (ADH)
- Keywords
- Autosomal Dominant Hypocalcemia, Hypocalcemia, ADH, Hypoparathyroidism
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Collaborators
- National Institutes of Health (NIH)
- Study start
- 18 Jul 2014 (actual)
- Primary completion
- 4 May 2015 (actual)
- Study completion
- 4 May 2015 (actual)
- First posted
- 30 Jul 2014 (estimated)
- Results
- Posted 21 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label study looking at the effects of NPSP795 (a selective calcium receptor antagonist) on activating mutations of the Calcium-sensing receptor in patients with Autosomal Dominant Hypocalcemia. Patients with ADH have low blood calcium levels and an inappropriately increased renal calcium excretion, decreased renal phosphate excretion, and hyperphosphatemia. PTH and blood calcium levels will be tested during and after the IV infusion of NPSP795. Concentrations of NPSP795 and length of time of IV infusion will vary depending on measured levels of ionized calcium.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NPSP795 | Experimental | Drug: NPSP795intravenous |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Subjects with a heterozygous activating mutation of the CaSR gene (ADH); if not previously confirmed, genetic testing will be performed at the screening visit
- At least 18 years of age
- Body mass index (BMI) ≥ 18.5 to < 39 kg/m2
Key exclusion criteria (9 listed)
- Diseases or conditions that might compromise any major body system or interfere with the pharmacokinetics of NPSP795
- History of treatment with PTH 1-84 or 1-34 within the previous 6 months
- History of hypocalcemia requiring frequent IV calcium infusions
- History of hypocalcemic seizure within the past 3 months
- Blood 25-hydroxy vitamin D level < 25 ng/mL. If subjects have a blood 25-hydroxy vitamin D level < 25 ng/mL at the outpatient screening visit, they will be prescribed vitamin D replacement. Once the 25-hydroxy vitamin D level is > 25 ng/mL, the subject will be eligible to continue on to the treatment phase of the study
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 |
|---|---|---|
| NPSP795 | Drug | NPSP795 |
Primary outcome
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Time frame: From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)
Number of Participants With Clinically Significant Vital Signs and Electrocardiogram (ECG) Abnormalities
Time frame: From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)
Number of Participants With Potentially Clinically Important Laboratory Abnormalities
Time frame: From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)
Number of Participants With Clinically Significant Abnormalities Related to Physical Examination
Time frame: From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)
Change From Baseline in Ionised Calcium
Time frame: 10 Minute (min) Infusion Time: within 5 min pre-dose; & post-dose 15, 30, 45, 60, 75, 90, 105 min, and 2, 2.5, 3, 3.5, & 4 hour (hr) 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 15, 30, 45, 60, 75, 90, 105 min, & 2, 2.5, 3, 3.5, 4, 5, and 8 hr
Change From Baseline in Serum Calcium
Time frame: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 1, 2, 3, 4, 8 12 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 1, 2, 3, 4, 8 12 hr.
Change From Baseline in Urinary Calcium
Time frame: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 1, 2, 3, 4, 8 12 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 1, 2, 3, 4, 8 12 hr.
Change From Baseline in Serum Parathyroid Hormone (PTH)
Time frame: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 5, 10, 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr
5 secondary outcomes
Area Under the Plasma Concentration Versus Time Curve (AUC[0-t]) of NPSP795
Time frame: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 5, 10, 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr
Area Under the Concentration Time Curve Extrapolated to Infinity (AUC0-infinity) of NPSP795
Time frame: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 5, 10, 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr
Maximum Observed Drug Concentration (Cmax) of NPSP795 in Plasma
Time frame: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 5, 10, 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr
Elimination Half-life (t1/2) of NPSP795 in Plasma
Time frame: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 5, 10, 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 8 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 15, 30 min, & 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 hr
Change From Baseline in Fractional Excretion of Calcium (FECa)
Time frame: 10 Minutes (min) Infusion Time: within 5 min pre-dose; & post-dose 1, 2, 3, 4, 8, 12 hours (hr). 3.5 hr Infusion Time: within 5 min pre-dose; & post-dose 1, 2, 3, 4, 8, 12 hr.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Study Director study director
Takeda
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NPSP795 in people with Autosomal Dominant Hypocalcemia (ADH), run by Shire at 1 site in United States.
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 3 inclusion and 9 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: finished, as of the sponsor's last update on 9 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) (time frame: From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)). The study lists 8 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 9 Aug 2021.