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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

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

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

Title

Area Under the Concentration Time Curve Extrapolated to Infinity (AUC0-infinity) of NPSP795

Time Frame

Title

Maximum Observed Drug Concentration (Cmax) of NPSP795 in Plasma

Time Frame

Title

Elimination Half-life (t1/2) of NPSP795 in Plasma

Time Frame

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

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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