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

NCT02204579 | Completed Phase 2 Results DMC

• 1 other identifier: CAL-C13-001
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Autosomal Dominant Hypocalcemia (ADH)

Keywords

Autosomal Dominant Hypocalcemia; Hypocalcemia; ADH; Hypoparathyroidism

Outcome Measures

Primary Outcomes (8)

• 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)

• 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)

• Number of Participants With Potentially Clinically Important Laboratory Abnormalities

  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

  From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)

• 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

• 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.

• 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.

• 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 Outcomes (5)

• 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

• 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

• 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

• 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

• 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.

Study Arms (1)

NPSP795

EXPERIMENTAL

intravenous

Drug: NPSP795

Interventions

NPSP795 DRUG

NPSP795

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• lead resting electrocardiogram (ECG) with clinically significant abnormalities
• Concomitant medications with the potential to interfere with NPSP795 metabolism
• History of thyroid or parathyroid surgery

Sponsors & Collaborators

• Shire: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

National Institute of Health (NIH)

Bethesda, Maryland, 20892-1103, United States

Location

MeSH Terms

Conditions

Hypercalciuric Hypocalcemia, Familial; Hypocalcemia; Hypoparathyroidism

Condition Hierarchy (Ancestors)

Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Water-Electrolyte Imbalance; Parathyroid Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2014
• First Posted: July 30, 2014
• Study Start: July 18, 2014
• Primary Completion: May 4, 2015
• Study Completion: May 4, 2015
• Last Updated: August 9, 2021
• Results First Posted: December 21, 2016

Record last verified: 2021-08

Locations

US (1)