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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
Shire
About
Eligibility
Locations
Arms
Outcomes
Full info

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

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

First Posted
July 28, 2014
Last Updated
August 5, 2021
Sponsor
Shire
Collaborators
National Institutes of Health (NIH)
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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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