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

Autosomal Dominant Hypocalcemia (ADH) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02204579
• Other study ID #: CAL-C13-001
• Status: Completed
• Phase: Phase 2
• Start date: July 18, 2014
• Est. completion date: May 4, 2015

Study information

• Verified date: August 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: May 4, 2015
• Est. primary completion date: May 4, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthrogryposis
• Autosomal Dominant Hypocalcemia (ADH)
• Hypocalcemia

Intervention

Drug:
• NPSP795

Locations

Country	Name	City	State
United States	National Institute of Health (NIH)	Bethesda	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Shire	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)		From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)
Primary	Number of Participants With Clinically Significant Vital Signs and Electrocardiogram (ECG) Abnormalities		From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)
Primary	Number of Participants With Potentially Clinically Important Laboratory Abnormalities		From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)
Primary	Number of Participants With Clinically Significant Abnormalities Related to Physical Examination		From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)
Primary	Change From Baseline in Ionised Calcium		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
Primary	Change From Baseline in Serum Calcium		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.
Primary	Change From Baseline in Urinary Calcium		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.
Primary	Change From Baseline in Serum Parathyroid Hormone (PTH)		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	Area Under the Plasma Concentration Versus Time Curve (AUC[0-t]) of NPSP795		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	Area Under the Concentration Time Curve Extrapolated to Infinity (AUC0-infinity) of NPSP795		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	Maximum Observed Drug Concentration (Cmax) of NPSP795 in Plasma		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	Elimination Half-life (t1/2) of NPSP795 in Plasma		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	Change From Baseline in Fractional Excretion of Calcium (FECa)		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.