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

Phase 2CompletedNCT02204579

Shire7 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Autosomal Dominant Hypocalcemia (ADH)

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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)

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)

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)

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)

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

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.

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.

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 Outcomes

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)

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.

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes