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
Primary Purpose
Autosomal Dominant Hypocalcemia (ADH)
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
NPSP795
Sponsored by
About this trial
This is an interventional treatment trial for Autosomal Dominant Hypocalcemia (ADH) focused on measuring Autosomal Dominant Hypocalcemia, Hypocalcemia, ADH, Hypoparathyroidism
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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
Sites / Locations
- National Institute of Health (NIH)
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
NPSP795
Arm Description
intravenous
Outcomes
Primary Outcome Measures
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Number of Participants With Clinically Significant Vital Signs and Electrocardiogram (ECG) Abnormalities
Number of Participants With Potentially Clinically Important Laboratory Abnormalities
Number of Participants With Clinically Significant Abnormalities Related to Physical Examination
Change From Baseline in Ionised Calcium
Change From Baseline in Serum Calcium
Change From Baseline in Urinary Calcium
Change From Baseline in Serum Parathyroid Hormone (PTH)
Secondary Outcome Measures
Area Under the Plasma Concentration Versus Time Curve (AUC[0-t]) of NPSP795
Area Under the Concentration Time Curve Extrapolated to Infinity (AUC0-infinity) of NPSP795
Maximum Observed Drug Concentration (Cmax) of NPSP795 in Plasma
Elimination Half-life (t1/2) of NPSP795 in Plasma
Change From Baseline in Fractional Excretion of Calcium (FECa)
Full Information
NCT ID
NCT02204579
First Posted
July 28, 2014
Last Updated
August 5, 2021
Sponsor
Shire
Collaborators
National Institutes of Health (NIH)
1. Study Identification
Unique Protocol Identification Number
NCT02204579
Brief Title
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
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
July 18, 2014 (Actual)
Primary Completion Date
May 4, 2015 (Actual)
Study Completion Date
May 4, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire
Collaborators
National Institutes of Health (NIH)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autosomal Dominant Hypocalcemia (ADH)
Keywords
Autosomal Dominant Hypocalcemia, Hypocalcemia, ADH, Hypoparathyroidism
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
NPSP795
Arm Type
Experimental
Arm Description
intravenous
Intervention Type
Drug
Intervention Name(s)
NPSP795
Primary Outcome Measure Information:
Title
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)
Title
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)
Title
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)
Title
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)
Title
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
Title
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.
Title
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.
Title
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
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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
Title
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
Title
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
National Institute of Health (NIH)
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892-1103
Country
United States
12. IPD Sharing Statement
Learn more about this trial
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
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