Clinical 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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Open-label Dose Escalation Study Evaluating the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Intravenous NPSP795 in Autosomal Dominant Hypocalcemia Due t

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.

Detailed Summary:
Sponsor: Shire

Current Primary Outcome:

• 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 at Specified Timepoint [ Time Frame: Baseline (Predose), 4 Hours and 8 Hours Postdose ]
• Change From Baseline in Serum Calcium at 12 Hours Postdose [ Time Frame: Baseline (Predose) to 12 Hours Postdose ]
• Change From Baseline in Urinary Calcium at 12 Hours Postdose [ Time Frame: Baseline (Predose) to 12 Hours Postdose ]
• Change From Baseline in Serum Parathyroid Hormone (PTH) at Specified Time Point [ Time Frame: Baseline (Predose), 5.5 Hours, 8 Hours Postdose ]

Original Primary Outcome: Measures will be secretion level of PTH by parathyroid cells and the concentration of extracellular calcium. [ Time Frame: PTH levels will be assessed at different time points depending on length of infusion0, 15 & 30 mins; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5, 6, 6.5, 7, 8, 8.5, 9, 9.5, 10 & 12 hrs ]

Current Secondary Outcome:

• Area Under the Plasma Concentration Versus Time Curve (AUC[0-t]) of NPSP795 [ Time Frame: Baseline (Predose), and 15, 30 Minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 and 8 Hours Postdose ]
• Area Under the Concentration Time Curve Extrapolated to Infinity (AUC0-infinity) of NPSP795 [ Time Frame: Baseline (Predose), and 15, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 and 8 Hours Postdose ]
• Maximum Observed Drug Concentration (Cmax) of NPSP795 in Plasma [ Time Frame: Baseline (Predose), and 15, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 and 8 Hours Postdose ]
• Elimination Half-life (t1/2) of NPSP795 in Plasma [ Time Frame: Baseline (Predose), and 15, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 5.5 and 8 Hours Postdose ]
• Change From Baseline in Fractional Excretion of Calcium (FECa) at 12 Hours Postdose [ Time Frame: Baseline (Predose) to 12 Hours Postdose ]

Original Secondary Outcome:

Information By: Shire

Dates:
Date Received: July 28, 2014
Date Started: July 2014
Date Completion:
Last Updated: October 27, 2016
Last Verified: October 2016