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| Name | Class |
|---|---|
| Celerion | INDUSTRY |
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To evaluate the PK, safety and tolerability of orally administered NPT520-34 in healthy subjects at single and multiple doses that may be therapeutically relevant.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NPT520-34 - SAD Cohort 1, Dose 1 (Unfed) | Other | Single ascending dose of orally administered capsule(s) NPT520-34: 125 mg OR Single dose of orally administered placebo capsule(s) to match dose. Unfed. |
|
| NPT520-34 - SAD Cohort 1, Dose 1 (Fed) | Other | Single ascending dose of orally administered capsule(s) NPT520-34: 125 mg OR Single dose of orally administered placebo capsule(s) to match dose. Fed. |
|
| NPT520-34 - SAD Cohort 2, Dose 2 | Other | Single ascending dose of orally administered capsule(s) NPT520-34: 250 mg OR Single dose of orally administered placebo capsule(s) to match dose. |
|
| NPT520-34 - SAD Cohort 3, Dose 3 | Other | Single ascending dose of orally administered capsule(s) NPT520-34: 500 mg OR Single dose of orally administered placebo capsule(s) to match dose. |
|
| NPT520-34 - SAD Cohort 4, Dose 4 | Other | Single ascending dose of orally administered capsule(s) NPT520-34: 1000 mg OR Single dose of orally administered placebo capsule(s) to match dose. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NPT520-34 (125 mg) | Drug | NPT520-34, 125 mg oral capsules (size 1) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety/Tolerability of Single Ascending Doses (125 mg, 250 mg, 500 mg and 1000 mg) | A) Incidence of clinically significant treatment-emergent changes in the following clinical measures: 1) physical examination, 2) suicidal ideation, 3) vital signs 4) continuous telemetry for 1 hour prior to dosing and for 2 hours post-dose, 5) continuous telemetry for 1 hour prior to dosing and for 2 hours post-dose. B) Incidence in clinical significant treatment-emergent changes in the following laboratory measures: 1) hematology, 2) clinical chemistry, 3) FSH (post-menopausal women only), 4) coagulation, 5) urinalysis C) Incidence of treatment-emergent adverse events D) Incidence of treatment-emergent serious adverse events | Baseline, Day 1, 2 3, 5 and 7 |
| Maximum observed plasma concentration of Single Ascending Doses (125 mg, 250 mg, 500 mg and 1000 mg) | Noncompartmental calculation of maximum observed plasma concentration (Cmax); | Day 1, 2, 3, 5, 7 |
| Time to maximum plasma concentration of Single Ascending Doses (125 mg, 250 mg, 500 mg and 1000 mg) | Noncompartmental calculation of time to maximum plasma concentration (Tmax); | Day 1, 2, 3, 5, 7 |
| Area under the plasma concentration-time curve from 0 hour to the time of the last quantifiable plasma concentration of Single Ascending Doses (125 mg, 250 mg, 500 mg and 1000 mg) | Noncompartmental calculation of area under the plasma concentration-time curve from 0 hour to the time of the last quantifiable plasma concentration [AUCt]; | Day 1, 2, 3, 5, 7 |
| Area under the plasma concentration-time curve extrapolated to infinity of Single Ascending Doses (125 mg, 250 mg, 500 mg and 1000 mg) | Noncompartmental calculation of area under the plasma concentration-time curve extrapolated to infinity (AUCinf) after dosing |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose of Single Ascending Doses (125 mg, 250 mg, 500 mg and 1000 mg) | A) 2/6 subjects assigned to NPT520-34 have SAEs or Grade ≥3 lab abnormalities, considered related to study drug B) 1/6 subjects assigned to NPT520-34 has liver function tests, which: 1) ALT or AST>3x ULN or bilirubin >1.5x ULN and related to study drug C) 1/6 subjects assigned to NPT520-34 have liver function tests, which: 1) ALT or AST>3x ULN or bilirubin>1.5x ULN and related to study drug D) 1/ 6 subjects assigned to NPT520-34 have kidney function tests, which: 1) eGFR<60 mL/min and relationship to study drug is considered related, 2) serum creatinine>2x above baseline and relationship to study drug is considered related E) 2/ 6 subjects assigned to NPT520-34 have kidney function tests, which: 1) eGFR<60 mL/min and related to study drug, 2) serum creatinine > 2x above baseline and related to study drug F) Any subject experiences a SAE related to study drug G) Further dose escalation poses inappropriate safety risk according to Sponsor/Investigator |
| Measure | Description | Time Frame |
|---|---|---|
| Exploratory Biomarkers of Single Ascending Doses (125 mg, 250 mg, 500 mg and 1000 mg) | To assess the following exploratory biomarkers: DHEA-S, DHEA, Cortisol Free, Copeptin, Osmolality Serum, Prolactin, FSH, LH, TSH, T3 Free, T4 free, Prostaglandin E2, Angiotensin II, Renin. | Baseline, Day 1, 2, Day 7 |
| Exploratory Biomarkers of Multiple Ascending Doses (250 mg and 500 mg) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Danielle Armas, M.D. | Celerion | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Celerion, Inc | Tempe | Arizona | 85283 | United States |
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| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| D000690 | Amyotrophic Lateral Sclerosis |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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|
| NPT520-34 - MAD Cohort 1, Dose 1 | Other | Multiple ascending dose of orally administered capsule(s) NPT520-34: TBD mg OR Single dose of orally administered placebo capsule(s) to match dose. |
|
| NPT520-34 - MAD Cohort 2, Dose 2 | Other | Multiple ascending dose of orally administered capsule(s) NPT520-34: TBD mg OR Single dose of orally administered placebo capsule(s) to match dose. |
|
| NPT520-34 - MAD Cohort 3, Dose 3 | Other | Multiple ascending dose of orally administered capsule(s) NPT520-34: TBD mg OR Single dose of orally administered placebo capsule(s) to match dose. |
|
| Placebos (125 mg) | Drug | Placebo, 125 mg oral capsules |
|
| Day 1, 2, 3, 5, 7 |
| Apparent oral clearance of Single Ascending Doses (125 mg, 250 mg, 500 mg and 1000 mg) | Noncompartmental calculation of apparent oral clearance (CL/F) | Day 1, 2, 3, 5, 7 |
| Apparent oral volume of distribution during the terminal phase of Single Ascending Doses (125 mg, 250 mg, 500 mg and 1000 mg) | Noncompartmental calculation of apparent oral volume of distribution during the terminal phase (Vz/F) | Day 1, 2, 3, 5, 7 |
| Mean residence time of Single Ascending Doses (125 mg, 250 mg, 500 mg and 1000 mg) | Noncompartmental calculation of mean residence time (MRT) | Day 1, 2, 3, 5, 7 |
| Terminal elimination half-life of Single Ascending Doses (125 mg, 250 mg, 500 mg and 1000 mg) | Noncompartmental calculation of terminal elimination half-life (T½); | Day 1, 2, 3, 5, 7 |
| Safety/Tolerability as measures of hematology, clinical chemistry, FSH, coagulation and urinalysis of multiple ascending doses (250 mg and 500 mg) | A) Incidence in clinical significant treatment-emergent changes in hematology B) Incidence in clinical significant treatment-emergent changes in clinical chemistry C) Incidence in clinical significant treatment-emergent changes in FSH (post-menopausal women only) D) Incidence in clinical significant treatment-emergent changes in coagulation E) Incidence in clinical significant treatment-emergent changes in urinalysis | Baseline, Day 2, 4, 7, 11, 12, 13, 14, and 21 |
| Safety/Tolerability as measures of vital signs and physical examination of multiple ascending doses (250 mg and 500 mg) | A) Incidence of clinically significant treatment-emergent changes in vital signs B) Incidence of clinically significant treatment-emergent changes in physical examination | Baseline, Day 1, 2, 7, 8, 9, 10, 11, 14, 16, 18 Day 21 |
| Safety/Tolerability as measures of continuous telemetry of multiple ascending doses (250 mg and 500 mg) | A) Incidence of clinically significant treatment-emergent changes in continuous telemetry | Baseline, Day 1, 2, 7, 8, 9, 10, 11, 14, and 15 |
| Safety/Tolerability as measures of suicidal ideation, 12-lead ECG, adverse events and serious adverse events of multiple ascending doses (250 mg and 500 mg) | A) Incidence in clinical significant treatment-emergent changes in suicidal ideation B) Incidence in clinical significant treatment-emergent changes in 12-lead ECG C) Incidence of treatment-emergent adverse events D) Incidence of treatment-emergent serious adverse events | Baseline, Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 18 Day 21 |
| Safety/Tolerability as measure of continuous ECG of Multiple Ascending Doses (250 mg and 500 mg) | A) Incidence in clinical significant treatment-emergent changes in continuous ECG telemetry | Baseline, Day 1, 7, and 14 |
| Maximum observed plasma concentration (Cmax) after dosing on Day 1 of Multiple Ascending Doses (250 mg, 500 mg) | Noncompartmental calculation of maximum observed plasma concentration (Cmax) after dosing on Day 1 | Baseline, Day 1 and 2 |
| Maximum observed concentration at steady-state after dosing on Day 14 of Multiple Ascending Doses (250 mg, 500 mg) | Noncompartmental calculation of maximum observed concentration at steady-state after dosing on Day 14 | Day 14 |
| Concentration observed at the end of the dosing interval of Multiple Ascending Doses (250 mg, 500 mg) | Noncompartmental calculation of concentration observed at the end of the dosing interval (Ctrough) | Day 14, 16, 18 |
| Time to max. plasma concentration after dosing on Day 1 of Multiple Ascending Doses (250 mg, 500 mg) | Noncompartmental calculation of time to max. plasma concentration after dosing on Day 1 | Day 1 |
| Time to reach Cmax,ss of Multiple Ascending Doses (250 mg, 500 mg) | Noncompartmental calculation of time to reach Cmax,ss | Day 14, 16, 18 and 21 |
| Area under the plasma concentration-time curve from 0 hour to the time of the last quantifiable plasma concentration of Multiple Ascending Doses (250 mg, 500 mg) | Noncompartmental calculation of area under the plasma concentration-time curve from 0 hour to the time of the last quantifiable plasma concentration (AUCt) | Baseline, Day 1, 2, 7, 8, 9, 10, 11, 14, 16, 18 and 21 |
| Area under the plasma concentration-time curve extrapolated to infinity after dosing of Multiple Ascending Doses (250 mg, 500 mg) | Noncompartmental calculation of area under the plasma concentration-time curve extrapolated to infinity after dosing (AUCinf) | Baseline, Day 1, 2, 7, 8, 9, 10, 11, 14, 16, 18 and 21 |
| Area under the concentration time curve from 0-24 hours after dosing on Day 1 of Multiple Ascending Doses (250 mg, 500 mg) | Noncompartmental calculation of the area under the concentration time curve from 0-24 hours after dosing on Day 1 (AUC0-24) | Day 1 |
| The area under the concentration time curve during a dosing interval (tau) at steady state after dosing on Day 14 of Multiple Ascending Doses (250 mg, 500 mg) | Noncompartmental calculation of the area under the concentration time curve during a dosing interval (tau) at steady state after dosing on Day 14 (AUCtau) | Baseline, Day 1, 2, 7, 8, 9, 10, 11, 14, 16, 18 and 21 |
| Apparent oral clearance of Multiple Ascending Doses (250 mg, 500 mg) | Noncompartmental calculation of apparent oral clearance (CL/F) | Day 1 |
| Apparent total plasma clearance after oral administration, calculated as Dose/AUCtau after dosing on Day 14 of Multiple Ascending Doses (250 mg, 500 mg) | Noncompartmental calculation of apparent total plasma clearance after oral (extravascular) administration (CL,ss/F), calculated as Dose/AUCtau after dosing on Day 14 | Day 14 |
| Apparent oral volume of distribution during the terminal phase of Multiple Ascending Doses (250 mg, 500 mg) | Noncompartmental calculation of apparent oral volume of distribution during the terminal phase (Vz/F) | Day 14, 16, 18 and 21 |
| Mean residence time of Multiple Ascending Doses (250 mg, 500 mg) | Noncompartmental calculation of mean residence time (MRT) | Baseline, Day 1, 2, 7, 8, 9, 10, 11, 14, 16, 18 and 21 |
| Terminal elimination half-life of Multiple Ascending Doses (250 mg, 500 mg) | Terminal elimination half-life | Day 14, 16, 18 and 21 |
| Day 1, 2, 3, 5, Day 7 |
| Maximum Tolerated Dose of Multiple Ascending Doses (250 mg and 500 mg) | A) 2/6 subjects assigned to NPT520-34 have SAEs or Grade ≥3 lab abnormalities, considered related to study drug B) 1/6 subjects assigned to NPT520-34 has liver function tests, which: 1) ALT or AST>3x ULN or bilirubin >1.5x ULN and related to study drug C) 1/6 subjects assigned to NPT520-34 have liver function tests, which: 1) ALT or AST>3x ULN or bilirubin>1.5x ULN and related to study drug D) 1/ 6 subjects assigned to NPT520-34 have kidney function tests, which: 1) eGFR<60 mL/min and relationship to study drug is considered related, 2) serum creatinine>2x above baseline and relationship to study drug is considered related E) 2/ 6 subjects assigned to NPT520-34 have kidney function tests, which: 1) eGFR<60 mL/min and related to study drug, 2) serum creatinine > 2x above baseline and related to study drug F) Any subject experiences a SAE related to study drug G) Further dose escalation poses inappropriate safety risk according to Sponsor/Investigator | Baseline, Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 18 Day 21 |
To assess the following exploratory biomarkers: DHEA-S, DHEA, Cortisol Free, Copeptin, Osmolality Serum, Prolactin, FSH, LH, TSH, T3 Free, T4 free, Prostaglandin E2, Angiotensin II, Renin. |
| Baseline, Day 1, Day 7, 14, and 21 |
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| D013118 | Spinal Cord Diseases |
| D016472 | Motor Neuron Disease |
| D057177 | TDP-43 Proteinopathies |
| D009468 | Neuromuscular Diseases |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |