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NCT Number: NCT02204579

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

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.

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Key information

Conditions

Autosomal Dominant Hypocalcemia (ADH) Calcium Metabolism Disorders Endocrine System Diseases Hypercalciuric Hypocalcemia, Familial Hypocalcemia Hypoparathyroidism Metabolic Diseases Nutritional and Metabolic Diseases Parathyroid Diseases Water-Electrolyte Imbalance

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

National Institute of Health (NIH)

Bethesda, Maryland, 20892-1103, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

NPSP795

Drug

Primary outcomes

  1. 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)

  2. 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)

  3. 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)

  4. 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)

  5. 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

  6. 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.

  7. 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.

  8. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

Sponsors and collaborators

Lead sponsor

Shire

Industry

Collaborators

  • National Institutes of Health (NIH)

Registry information

Official study 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

Important dates

Study start
2014
Primary completion
2015
Study completion
2015
First posted
Jul 30, 2014
Registry last updated
Aug 9, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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