Autosomal Dominant Hypocalcemia (ADH)
Conditions
Keywords
Autosomal Dominant Hypocalcemia, Hypocalcemia, ADH, Hypoparathyroidism
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.
Interventions
DRUGNPSP795
Sponsors
National Institutes of Health (NIH)
Shire
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
| 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. |
| 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) |
Secondary
| Measure | Time frame |
|---|---|
| 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. |
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NPSP795 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. | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Screen failures | 2 |
Baseline characteristics
| Characteristic | NPSP795 |
|---|---|
| Age, Continuous | 39.8 Years STANDARD_DEVIATION 15.2 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 5 |
| serious Total, serious adverse events | 1 / 5 |
Outcome results
Primary
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NPSP795 | Change From Baseline in Ionised Calcium | Baseline | 0.972 millimole/liter (mmol/L) | Standard Deviation 0.058 |
| NPSP795 | Change From Baseline in Ionised Calcium | Change at 8 Hours Post dose | NA millimole/liter (mmol/L) | — |
| NPSP795 | Change From Baseline in Ionised Calcium | Change at 4 Hours Post dose | -0.016 millimole/liter (mmol/L) | Standard Deviation 0.027 |
| NPSP795 on Day 2 (15 mg/3.5 Hours) | Change From Baseline in Ionised Calcium | Change at 4 Hours Post dose | 0.010 millimole/liter (mmol/L) | Standard Deviation 0.026 |
| NPSP795 on Day 2 (15 mg/3.5 Hours) | Change From Baseline in Ionised Calcium | Baseline | 0.950 millimole/liter (mmol/L) | Standard Deviation 0.054 |
| NPSP795 on Day 2 (15 mg/3.5 Hours) | Change From Baseline in Ionised Calcium | Change at 8 Hours Post dose | -0.034 millimole/liter (mmol/L) | Standard Deviation 0.044 |
| NPSP795 on Day 3 (30 mg/3.5 Hours) | Change From Baseline in Ionised Calcium | Change at 4 Hours Post dose | -0.014 millimole/liter (mmol/L) | Standard Deviation 0.023 |
| NPSP795 on Day 3 (30 mg/3.5 Hours) | Change From Baseline in Ionised Calcium | Baseline | 0.986 millimole/liter (mmol/L) | Standard Deviation 0.045 |
| NPSP795 on Day 3 (30 mg/3.5 Hours) | Change From Baseline in Ionised Calcium | Change at 8 Hours Post dose | -0.040 millimole/liter (mmol/L) | Standard Deviation 0.06 |
| NPSP795 on Day 4 (30 mg/3.5 Hours) | Change From Baseline in Ionised Calcium | Baseline | 0.933 millimole/liter (mmol/L) | Standard Deviation 0.055 |
| NPSP795 on Day 4 (30 mg/3.5 Hours) | Change From Baseline in Ionised Calcium | Change at 8 Hours Post dose | -0.033 millimole/liter (mmol/L) | Standard Deviation 0.046 |
| NPSP795 on Day 4 (30 mg/3.5 Hours) | Change From Baseline in Ionised Calcium | Change at 4 Hours Post dose | -0.030 millimole/liter (mmol/L) | Standard Deviation 0.046 |
| NPSP795 on Day 4 (50 mg/3.5 Hours) | Change From Baseline in Ionised Calcium | Change at 4 Hours Post dose | -0.015 millimole/liter (mmol/L) | Standard Deviation 0.035 |
| NPSP795 on Day 4 (50 mg/3.5 Hours) | Change From Baseline in Ionised Calcium | Baseline | 1.025 millimole/liter (mmol/L) | Standard Deviation 0.078 |
| NPSP795 on Day 4 (50 mg/3.5 Hours) | Change From Baseline in Ionised Calcium | Change at 8 Hours Post dose | -0.060 millimole/liter (mmol/L) | Standard Deviation 0.028 |
Primary
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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NPSP795 | Change From Baseline in Serum Calcium | Baseline | 1.914 millimole/liter (mmol/L) | Standard Deviation 0.157 |
| NPSP795 | Change From Baseline in Serum Calcium | Change at 12 Hours Postdose | -0.114 millimole/liter (mmol/L) | Standard Deviation 0.141 |
| NPSP795 on Day 2 (15 mg/3.5 Hours) | Change From Baseline in Serum Calcium | Baseline | 1.790 millimole/liter (mmol/L) | Standard Deviation 0.125 |
| NPSP795 on Day 2 (15 mg/3.5 Hours) | Change From Baseline in Serum Calcium | Change at 12 Hours Postdose | -0.042 millimole/liter (mmol/L) | Standard Deviation 0.054 |
| NPSP795 on Day 3 (30 mg/3.5 Hours) | Change From Baseline in Serum Calcium | Baseline | 1.852 millimole/liter (mmol/L) | Standard Deviation 0.132 |
| NPSP795 on Day 3 (30 mg/3.5 Hours) | Change From Baseline in Serum Calcium | Change at 12 Hours Postdose | -0.106 millimole/liter (mmol/L) | Standard Deviation 0.079 |
| NPSP795 on Day 4 (30 mg/3.5 Hours) | Change From Baseline in Serum Calcium | Change at 12 Hours Postdose | -0.040 millimole/liter (mmol/L) | Standard Deviation 0.053 |
| NPSP795 on Day 4 (30 mg/3.5 Hours) | Change From Baseline in Serum Calcium | Baseline | 1.677 millimole/liter (mmol/L) | Standard Deviation 0.135 |
| NPSP795 on Day 4 (50 mg/3.5 Hours) | Change From Baseline in Serum Calcium | Baseline | 1.980 millimole/liter (mmol/L) | Standard Deviation 0.184 |
| NPSP795 on Day 4 (50 mg/3.5 Hours) | Change From Baseline in Serum Calcium | Change at 12 Hours Postdose | -0.270 millimole/liter (mmol/L) | Standard Deviation 0.057 |
Primary
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NPSP795 | Change From Baseline in Serum Parathyroid Hormone (PTH) | Baseline | 7.32 nanogram/liter (ng/L) | Standard Deviation 2.93 |
| NPSP795 | Change From Baseline in Serum Parathyroid Hormone (PTH) | Change at 8 Hours Postdose | 0.60 nanogram/liter (ng/L) | Standard Deviation 1.56 |
| NPSP795 | Change From Baseline in Serum Parathyroid Hormone (PTH) | Change at 5.5 Hours Postdose | NA nanogram/liter (ng/L) | — |
| NPSP795 on Day 2 (15 mg/3.5 Hours) | Change From Baseline in Serum Parathyroid Hormone (PTH) | Change at 5.5 Hours Postdose | 0.84 nanogram/liter (ng/L) | Standard Deviation 0.86 |
| NPSP795 on Day 2 (15 mg/3.5 Hours) | Change From Baseline in Serum Parathyroid Hormone (PTH) | Baseline | 9.14 nanogram/liter (ng/L) | Standard Deviation 3.29 |
| NPSP795 on Day 2 (15 mg/3.5 Hours) | Change From Baseline in Serum Parathyroid Hormone (PTH) | Change at 8 Hours Postdose | NA nanogram/liter (ng/L) | — |
| NPSP795 on Day 3 (30 mg/3.5 Hours) | Change From Baseline in Serum Parathyroid Hormone (PTH) | Change at 5.5 Hours Postdose | 1.92 nanogram/liter (ng/L) | Standard Deviation 1.53 |
| NPSP795 on Day 3 (30 mg/3.5 Hours) | Change From Baseline in Serum Parathyroid Hormone (PTH) | Baseline | 9.58 nanogram/liter (ng/L) | Standard Deviation 5.32 |
| NPSP795 on Day 3 (30 mg/3.5 Hours) | Change From Baseline in Serum Parathyroid Hormone (PTH) | Change at 8 Hours Postdose | NA nanogram/liter (ng/L) | — |
| NPSP795 on Day 4 (30 mg/3.5 Hours) | Change From Baseline in Serum Parathyroid Hormone (PTH) | Baseline | 12.80 nanogram/liter (ng/L) | Standard Deviation 8.68 |
| NPSP795 on Day 4 (30 mg/3.5 Hours) | Change From Baseline in Serum Parathyroid Hormone (PTH) | Change at 8 Hours Postdose | NA nanogram/liter (ng/L) | — |
| NPSP795 on Day 4 (30 mg/3.5 Hours) | Change From Baseline in Serum Parathyroid Hormone (PTH) | Change at 5.5 Hours Postdose | 0.13 nanogram/liter (ng/L) | Standard Deviation 1.5 |
| NPSP795 on Day 4 (50 mg/3.5 Hours) | Change From Baseline in Serum Parathyroid Hormone (PTH) | Change at 5.5 Hours Postdose | 1.75 nanogram/liter (ng/L) | Standard Deviation 0.64 |
| NPSP795 on Day 4 (50 mg/3.5 Hours) | Change From Baseline in Serum Parathyroid Hormone (PTH) | Baseline | 7.40 nanogram/liter (ng/L) | Standard Deviation 3.54 |
| NPSP795 on Day 4 (50 mg/3.5 Hours) | Change From Baseline in Serum Parathyroid Hormone (PTH) | Change at 8 Hours Postdose | NA nanogram/liter (ng/L) | — |
Primary
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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NPSP795 | Change From Baseline in Urinary Calcium | Baseline | 3.302 millimole/liter (mmol/L) | Standard Deviation 2.283 |
| NPSP795 | Change From Baseline in Urinary Calcium | Change at 12 Hours Postdose | -0.590 millimole/liter (mmol/L) | Standard Deviation 0.861 |
| NPSP795 on Day 2 (15 mg/3.5 Hours) | Change From Baseline in Urinary Calcium | Baseline | 3.912 millimole/liter (mmol/L) | Standard Deviation 3.299 |
| NPSP795 on Day 2 (15 mg/3.5 Hours) | Change From Baseline in Urinary Calcium | Change at 12 Hours Postdose | -2.162 millimole/liter (mmol/L) | Standard Deviation 2.027 |
| NPSP795 on Day 3 (30 mg/3.5 Hours) | Change From Baseline in Urinary Calcium | Baseline | 2.936 millimole/liter (mmol/L) | Standard Deviation 1.75 |
| NPSP795 on Day 3 (30 mg/3.5 Hours) | Change From Baseline in Urinary Calcium | Change at 12 Hours Postdose | -1.188 millimole/liter (mmol/L) | Standard Deviation 1.634 |
| NPSP795 on Day 4 (30 mg/3.5 Hours) | Change From Baseline in Urinary Calcium | Change at 12 Hours Postdose | -1.190 millimole/liter (mmol/L) | Standard Deviation 1.46 |
| NPSP795 on Day 4 (30 mg/3.5 Hours) | Change From Baseline in Urinary Calcium | Baseline | 2.537 millimole/liter (mmol/L) | Standard Deviation 1.968 |
| NPSP795 on Day 4 (50 mg/3.5 Hours) | Change From Baseline in Urinary Calcium | Baseline | 2.065 millimole/liter (mmol/L) | Standard Deviation 1.916 |
| NPSP795 on Day 4 (50 mg/3.5 Hours) | Change From Baseline in Urinary Calcium | Change at 12 Hours Postdose | -0.755 millimole/liter (mmol/L) | Standard Deviation 1.082 |
Primary
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)
Population: Safety population included all participants who received at least 1 minute of study drug infusion (both pre-amendment and post-amendment participants).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NPSP795 | Number of Participants With Clinically Significant Abnormalities Related to Physical Examination | 1 participants |
Primary
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)
Population: Safety population included all participants who received at least 1 minute of study drug infusion (both pre-amendment and post-amendment participants).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NPSP795 | Number of Participants With Clinically Significant Vital Signs and Electrocardiogram (ECG) Abnormalities | 0 participants |
Primary
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)
Population: Safety population included all participants who received at least 1 minute of study drug infusion (pre-amendment and post-amendment).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NPSP795 | Number of Participants With Potentially Clinically Important Laboratory Abnormalities | 1 participants |
Primary
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)
Population: Safety population included all participants who received at least 1 minute of study drug infusion (pre-amendment and post-amendment).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NPSP795 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Participants with TEAEs | 3 participants |
| NPSP795 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Participants with TESAEs | 1 participants |
Secondary
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NPSP795 | Area Under the Concentration Time Curve Extrapolated to Infinity (AUC0-infinity) of NPSP795 | 2.672 nanogram*hour per milliliter(ng·h/mL) | Standard Deviation 1.775 |
| NPSP795 on Day 2 (15 mg/3.5 Hours) | Area Under the Concentration Time Curve Extrapolated to Infinity (AUC0-infinity) of NPSP795 | 5.572 nanogram*hour per milliliter(ng·h/mL) | Standard Deviation 2.724 |
| NPSP795 on Day 3 (30 mg/3.5 Hours) | Area Under the Concentration Time Curve Extrapolated to Infinity (AUC0-infinity) of NPSP795 | 5.437 nanogram*hour per milliliter(ng·h/mL) | Standard Deviation 2.587 |
| NPSP795 on Day 4 (30 mg/3.5 Hours) | Area Under the Concentration Time Curve Extrapolated to Infinity (AUC0-infinity) of NPSP795 | 7.648 nanogram*hour per milliliter(ng·h/mL) | Standard Deviation 3.607 |
| NPSP795 on Day 4 (50 mg/3.5 Hours) | Area Under the Concentration Time Curve Extrapolated to Infinity (AUC0-infinity) of NPSP795 | 4.521 nanogram*hour per milliliter(ng·h/mL) | Standard Deviation 2.991 |
Secondary
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NPSP795 | Area Under the Plasma Concentration Versus Time Curve (AUC[0-t]) of NPSP795 | 309.512 nanogram*hour per millilitre (ng·h/mL) | Standard Deviation 122.601 |
| NPSP795 on Day 2 (15 mg/3.5 Hours) | Area Under the Plasma Concentration Versus Time Curve (AUC[0-t]) of NPSP795 | 795.766 nanogram*hour per millilitre (ng·h/mL) | Standard Deviation 294.345 |
| NPSP795 on Day 3 (30 mg/3.5 Hours) | Area Under the Plasma Concentration Versus Time Curve (AUC[0-t]) of NPSP795 | 1561.746 nanogram*hour per millilitre (ng·h/mL) | Standard Deviation 546.479 |
| NPSP795 on Day 4 (30 mg/3.5 Hours) | Area Under the Plasma Concentration Versus Time Curve (AUC[0-t]) of NPSP795 | 1657.057 nanogram*hour per millilitre (ng·h/mL) | Standard Deviation 650.156 |
| NPSP795 on Day 4 (50 mg/3.5 Hours) | Area Under the Plasma Concentration Versus Time Curve (AUC[0-t]) of NPSP795 | 2251.818 nanogram*hour per millilitre (ng·h/mL) | Standard Deviation 568.782 |
Secondary
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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NPSP795 | Change From Baseline in Fractional Excretion of Calcium (FECa) | FECa: Baseline | 0.030 Fraction of excretion | Standard Deviation 0.023 |
| NPSP795 | Change From Baseline in Fractional Excretion of Calcium (FECa) | FECa: Change at 12 Hours Postdose | 0.002 Fraction of excretion | Standard Deviation 0.005 |
| NPSP795 on Day 2 (15 mg/3.5 Hours) | Change From Baseline in Fractional Excretion of Calcium (FECa) | FECa: Baseline | 0.031 Fraction of excretion | Standard Deviation 0.017 |
| NPSP795 on Day 2 (15 mg/3.5 Hours) | Change From Baseline in Fractional Excretion of Calcium (FECa) | FECa: Change at 12 Hours Postdose | 0.002 Fraction of excretion | Standard Deviation 0.012 |
| NPSP795 on Day 3 (30 mg/3.5 Hours) | Change From Baseline in Fractional Excretion of Calcium (FECa) | FECa: Baseline | 0.027 Fraction of excretion | Standard Deviation 0.014 |
| NPSP795 on Day 3 (30 mg/3.5 Hours) | Change From Baseline in Fractional Excretion of Calcium (FECa) | FECa: Change at 12 Hours Postdose | 0.001 Fraction of excretion | Standard Deviation 0.011 |
| NPSP795 on Day 4 (30 mg/3.5 Hours) | Change From Baseline in Fractional Excretion of Calcium (FECa) | FECa: Change at 12 Hours Postdose | -0.009 Fraction of excretion | Standard Deviation 0.018 |
| NPSP795 on Day 4 (30 mg/3.5 Hours) | Change From Baseline in Fractional Excretion of Calcium (FECa) | FECa: Baseline | 0.030 Fraction of excretion | Standard Deviation 0.011 |
| NPSP795 on Day 4 (50 mg/3.5 Hours) | Change From Baseline in Fractional Excretion of Calcium (FECa) | FECa: Baseline | 0.026 Fraction of excretion | Standard Deviation 0.032 |
| NPSP795 on Day 4 (50 mg/3.5 Hours) | Change From Baseline in Fractional Excretion of Calcium (FECa) | FECa: Change at 12 Hours Postdose | 0.002 Fraction of excretion | Standard Deviation 0.007 |
Secondary
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NPSP795 | Elimination Half-life (t1/2) of NPSP795 in Plasma | 3.013 hour | Standard Deviation 0.612 |
| NPSP795 on Day 2 (15 mg/3.5 Hours) | Elimination Half-life (t1/2) of NPSP795 in Plasma | 3.913 hour | Standard Deviation 0.222 |
| NPSP795 on Day 3 (30 mg/3.5 Hours) | Elimination Half-life (t1/2) of NPSP795 in Plasma | 4.213 hour | Standard Deviation 0.449 |
| NPSP795 on Day 4 (30 mg/3.5 Hours) | Elimination Half-life (t1/2) of NPSP795 in Plasma | 3.839 hour | Standard Deviation 0.294 |
| NPSP795 on Day 4 (50 mg/3.5 Hours) | Elimination Half-life (t1/2) of NPSP795 in Plasma | 4.000 hour | Standard Deviation 0 |
Secondary
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NPSP795 | Maximum Observed Drug Concentration (Cmax) of NPSP795 in Plasma | 301.900 nanogram/milliliter (ng/mL) | Standard Deviation 120.664 |
| NPSP795 on Day 2 (15 mg/3.5 Hours) | Maximum Observed Drug Concentration (Cmax) of NPSP795 in Plasma | 745.335 nanogram/milliliter (ng/mL) | Standard Deviation 254.205 |
| NPSP795 on Day 3 (30 mg/3.5 Hours) | Maximum Observed Drug Concentration (Cmax) of NPSP795 in Plasma | 1467.102 nanogram/milliliter (ng/mL) | Standard Deviation 475.343 |
| NPSP795 on Day 4 (30 mg/3.5 Hours) | Maximum Observed Drug Concentration (Cmax) of NPSP795 in Plasma | 1515.086 nanogram/milliliter (ng/mL) | Standard Deviation 548.056 |
| NPSP795 on Day 4 (50 mg/3.5 Hours) | Maximum Observed Drug Concentration (Cmax) of NPSP795 in Plasma | 2141.500 nanogram/milliliter (ng/mL) | Standard Deviation 475.706 |