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

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02204579
• Collaborator: National Institutes of Health (NIH) (NIH)
• Enrollment: 7
• Location: 1
• Arm: 1
• Actual Duration (Months): 9.5
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Autosomal Dominant Hypocalcemia (ADH)	Drug: NPSP795	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Jul 18, 2014
• Actual Primary Completion Date: May 4, 2015
• Actual Study Completion Date: May 4, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NPSP795 intravenous	Drug: NPSP795

Outcome Measures

Primary Outcome Measures

1. 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)]

2. 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)]

3. Number of Participants With Potentially Clinically Important Laboratory Abnormalities [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 [From Day 1 up to safety follow-up assessment (upto Day 17 after discharge)]

5. 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]

6. 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.]

7. 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.]

8. 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 Outcome Measures

1. 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]

2. 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]

3. 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]

4. 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]

5. 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.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institute of Health (NIH)	Bethesda	Maryland	United States	20892-1103

Sponsors and Collaborators

• Shire
• National Institutes of Health (NIH)

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT02204579
• Other Study ID Numbers: CAL-C13-001
• First Posted: Jul 30, 2014
• Last Update Posted: Aug 9, 2021
• Last Verified: Aug 1, 2021

• Keywords provided by Shire: Autosomal Dominant Hypocalcemia; Hypocalcemia; ADH; Hypoparathyroidism
• Additional relevant MeSH terms: Arthrogryposis; Hypocalcemia

Study Results

Participant Flow

Arm/Group Title	NPSP795
Arm/Group Description	NPSP795 administered Intravenous (IV) infusion for 10 min on Day 1 if certain criteria for ionized calcium and/or blood parathyroid hormone (PTH) were met, an infusion was administered for either 10 min or 3.5 hours on Days 2 & 3, according to a predefined dose escalation scheme. NPSP795 was administered as a 3.5-hour infusion on Day 4, or the participant underwent discharge procedures.
Period Title: Overall Study
STARTED	7
Participants Started in Pre-Amendment	2
Participants Started in Post-Amendment	5
Treated	5
COMPLETED	5
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	NPSP795
Arm/Group Description	NPSP795 administered Intravenous (IV) infusion for 10 min on Day 1 if certain criteria for ionized calcium and/or blood parathyroid hormone (PTH) were met, an infusion was administered for either 10 min or 3.5 hours on Days 2 & 3, according to a predefined dose escalation scheme. NPSP795 was administered as a 3.5-hour infusion on Day 4, or the participant underwent discharge procedures.
Overall Participants	5
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	39.8 (15.2)
Sex: Female, Male (Count of Participants)
Female	2 40%
Male	3 60%

Outcome Measures

1. Primary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 minute of study drug infusion (pre-amendment and post-amendment).

Arm/Group Title	NPSP795
Arm/Group Description	NPSP795 administered Intravenous (IV) infusion for 10 min on Day 1 if certain criteria for ionized calcium and/or blood parathyroid hormone (PTH) were met, an infusion was administered for either 10 min or 3.5 hours on Days 2 & 3, according to a predefined dose escalation scheme. NPSP795 was administered as a 3.5-hour infusion on Day 4, or the participant underwent discharge procedures.
Measure Participants	5
Participants with TEAEs	3 60%
Participants with TESAEs	1 20%

2. Primary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 minute of study drug infusion (both pre-amendment and post-amendment participants).

Arm/Group Title	NPSP795
Arm/Group Description	NPSP795 administered Intravenous (IV) infusion for 10 min on Day 1 if certain criteria for ionized calcium and/or blood parathyroid hormone (PTH) were met, an infusion was administered for either 10 min or 3.5 hours on Days 2 & 3, according to a predefined dose escalation scheme. NPSP795 was administered as a 3.5-hour infusion on Day 4, or the participant underwent discharge procedures.
Measure Participants	5
Number [participants]	0 0%

3. Primary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 minute of study drug infusion (pre-amendment and post-amendment).

Arm/Group Title	NPSP795
Arm/Group Description	NPSP795 administered Intravenous (IV) infusion for 10 min on Day 1 if certain criteria for ionized calcium and/or blood parathyroid hormone (PTH) were met, an infusion was administered for either 10 min or 3.5 hours on Days 2 & 3, according to a predefined dose escalation scheme. NPSP795 was administered as a 3.5-hour infusion on Day 4, or the participant underwent discharge procedures.
Measure Participants	5
Number [participants]	1 20%

4. Primary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 minute of study drug infusion (both pre-amendment and post-amendment participants).

Arm/Group Title	NPSP795
Arm/Group Description	NPSP795 administered Intravenous (IV) infusion for 10 min on Day 1 if certain criteria for ionized calcium and/or blood parathyroid hormone (PTH) were met, an infusion was administered for either 10 min or 3.5 hours on Days 2 & 3, according to a predefined dose escalation scheme. NPSP795 was administered as a 3.5-hour infusion on Day 4, or the participant underwent discharge procedures.
Measure Participants	5
Number [participants]	1 20%

5. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Post-amendment pharmacodynamic (PD) analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PD measurement on at least 1 day of infusion. Here, n=number of participants analysed for specified category at the specified time points in each arm respectively.

Arm/Group Title	NPSP795 on Day 1 (5 mg/10 Minutes)	NPSP795 on Day 2 (15 mg/3.5 Hours)	NPSP795 on Day 3 (30 mg/3.5 Hours)	NPSP795 on Day 4 (30 mg/3.5 Hours)	NPSP795 on Day 4 (50 mg/3.5 Hours)
Arm/Group Description
Measure Participants	5	5	5	5	5
Baseline	0.972 (0.058)	0.950 (0.054)	0.986 (0.045)	0.933 (0.055)	1.025 (0.078)
Change at 4 Hours Post dose	-0.016 (0.027)	0.010 (0.026)	-0.014 (0.023)	-0.030 (0.046)	-0.015 (0.035)
Change at 8 Hours Post dose	NA (NA)	-0.034 (0.044)	-0.040 (0.060)	-0.033 (0.046)	-0.060 (0.028)

6. Primary Outcome

Title	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.

Outcome Measure Data

Analysis Population Description

Post-amendment PD analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PD measurement on at least 1 day of infusion. Here, n=number of participants analysed for specified category at the specified time points in each arm respectively.

Arm/Group Title	NPSP795 on Day 1 (5 mg/10 Minutes)	NPSP795 on Day 2 (15 mg/3.5 Hours)	NPSP795 on Day 3 (30 mg/3.5 Hours)	NPSP795 on Day 4 (30 mg/3.5 Hours)	NPSP795 on Day 4 (50 mg/3.5 Hours)
Arm/Group Description
Measure Participants	5	5	5	5	5
Baseline	1.914 (0.157)	1.790 (0.125)	1.852 (0.132)	1.677 (0.135)	1.980 (0.184)
Change at 12 Hours Postdose	-0.114 (0.141)	-0.042 (0.054)	-0.106 (0.079)	-0.040 (0.053)	-0.270 (0.057)

7. Primary Outcome

Title	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.

Outcome Measure Data

Analysis Population Description

PD analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PD measurement on at least 1 day of infusion. Here, n=number of participants analysed for specified category at the specified time points in each arm respectively.

Arm/Group Title	NPSP795 on Day 1 (5 mg/10 Minutes)	NPSP795 on Day 2 (15 mg/3.5 Hours)	NPSP795 on Day 3 (30 mg/3.5 Hours)	NPSP795 on Day 4 (30 mg/3.5 Hours)	NPSP795 on Day 4 (50 mg/3.5 Hours)
Arm/Group Description
Measure Participants	5	5	5	5	5
Baseline	3.302 (2.283)	3.912 (3.299)	2.936 (1.750)	2.537 (1.968)	2.065 (1.916)
Change at 12 Hours Postdose	-0.590 (0.861)	-2.162 (2.027)	-1.188 (1.634)	-1.190 (1.460)	-0.755 (1.082)

8. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Post amendment PD analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PD measurement on at least 1 day of infusion. Here, n=number of participants analysed for specified category at the specified time points in each arm respectively.

Arm/Group Title	NPSP795 on Day 1 (5 mg/10 Minutes)	NPSP795 on Day 2 (15 mg/3.5 Hours)	NPSP795 on Day 3 (30 mg/3.5 Hours)	NPSP795 on Day 4 (30 mg/3.5 Hours)	NPSP795 on Day 4 (50 mg/3.5 Hours)
Arm/Group Description
Measure Participants	5	5	5	5	5
Baseline	7.32 (2.93)	9.14 (3.29)	9.58 (5.32)	12.80 (8.68)	7.40 (3.54)
Change at 5.5 Hours Postdose	NA (NA)	0.84 (0.86)	1.92 (1.53)	0.13 (1.50)	1.75 (0.64)
Change at 8 Hours Postdose	0.60 (1.56)	NA (NA)	NA (NA)	NA (NA)	NA (NA)

9. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Post amendment pharmacokinetic (PK) analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PK measurement on at least 1 day of infusion.

Arm/Group Title	NPSP795 on Day 1 (5 mg/10 Minutes)	NPSP795 on Day 2 (15 mg/3.5 Hours)	NPSP795 on Day 3 (30 mg/3.5 Hours)	NPSP795 on Day 4 (30 mg/3.5 Hours)	NPSP795 on Day 4 (50 mg/3.5 Hours)
Arm/Group Description
Measure Participants	5	5	5	3	2
Mean (Standard Deviation) [nanogram*hour per millilitre (ng·h/mL)]	309.512 (122.601)	795.766 (294.345)	1561.746 (546.479)	1657.057 (650.156)	2251.818 (568.782)

10. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Post amendment PK analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PK measurement on at least 1 day of infusion.

Arm/Group Title	NPSP795 on Day 1 (5 mg/10 Minutes)	NPSP795 on Day 2 (15 mg/3.5 Hours)	NPSP795 on Day 3 (30 mg/3.5 Hours)	NPSP795 on Day 4 (30 mg/3.5 Hours)	NPSP795 on Day 4 (50 mg/3.5 Hours)
Arm/Group Description
Measure Participants	5	5	5	3	2
Mean (Standard Deviation) [nanogram*hour per milliliter(ng·h/mL)]	2.672 (1.775)	5.572 (2.724)	5.437 (2.587)	7.648 (3.607)	4.521 (2.991)

11. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Post amendment PK analysis population included all randomized participants who received at least 5 minutes of the study drug infusion and had at least one PK measurement on at least one day of infusion.

Arm/Group Title	NPSP795 on Day 1 (5 mg/10 Minutes)	NPSP795 on Day 2 (15 mg/3.5 Hours)	NPSP795 on Day 3 (30 mg/3.5 Hours)	NPSP795 on Day 4 (30 mg/3.5 Hours)	NPSP795 on Day 4 (50 mg/3.5 Hours)
Arm/Group Description
Measure Participants	5	5	5	3	2
Mean (Standard Deviation) [nanogram/milliliter (ng/mL)]	301.900 (120.664)	745.335 (254.205)	1467.102 (475.343)	1515.086 (548.056)	2141.500 (475.706)

12. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Post amendment PK analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PK measurement on at least 1 day of infusion.

Arm/Group Title	NPSP795 on Day 1 (5 mg/10 Minutes)	NPSP795 on Day 2 (15 mg/3.5 Hours)	NPSP795 on Day 3 (30 mg/3.5 Hours)	NPSP795 on Day 4 (30 mg/3.5 Hours)	NPSP795 on Day 4 (50 mg/3.5 Hours)
Arm/Group Description
Measure Participants	5	5	5	3	2
Mean (Standard Deviation) [hour]	3.013 (0.612)	3.913 (0.222)	4.213 (0.449)	3.839 (0.294)	4.000 (0.000)

13. Secondary Outcome

Title	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.

Outcome Measure Data

Analysis Population Description

Post-amendment PD analysis population included all participants who received at least 5 minutes of the study drug infusion and had at least one PD measurement on at least 1 day of infusion. Here n=number of participants analysed for specified category at the specified time points in each arm respectively.

Arm/Group Title	NPSP795 on Day 1 (5 mg/10 Minutes)	NPSP795 on Day 2 (15 mg/3.5 Hours)	NPSP795 on Day 3 (30 mg/3.5 Hours)	NPSP795 on Day 4 (30 mg/3.5 Hours)	NPSP795 on Day 4 (50 mg/3.5 Hours)
Arm/Group Description
Measure Participants	5	5	5	5	5
FECa: Baseline	0.030 (0.023)	0.031 (0.017)	0.027 (0.014)	0.030 (0.011)	0.026 (0.032)
FECa: Change at 12 Hours Postdose	0.002 (0.005)	0.002 (0.012)	0.001 (0.011)	-0.009 (0.018)	0.002 (0.007)

Adverse Events

Time Frame	From the sign of informed consent form (Day -93) up to safety follow-up assessment (upto Day 17 after discharge)
Arm/Group Title	NPSP795
Arm/Group Description	NPSP795 administered Intravenous (IV) infusion for 10 min on Day 1 if certain criteria for ionized calcium and/or blood parathyroid hormone (PTH) were met, an infusion was administered for either 10 min or 3.5 hours on Days 2 & 3, according to a predefined dose escalation scheme. NPSP795 was administered as a 3.5-hour infusion on Day 4, or the participant underwent discharge procedures.
All Cause Mortality
	NPSP795
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	NPSP795
	Affected / at Risk (%)	# Events
Total	1/5 (20%)
Hepatobiliary disorders
Cholelithiasis	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	NPSP795
	Affected / at Risk (%)	# Events
Total	3/5 (60%)
Hepatobiliary disorders
Cholelithiasis	1/5 (20%)	1
Immune system disorders
Hypersensitivity reaction	1/5 (20%)	2
Reproductive system and breast disorders
Nipple pain	1/5 (20%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.