Safety and Pharmacokinetic Study of NPT 2042 Soft-gelatin Capsules Administered Orally to Healthy Adult Subjects
Primary Purpose
Epilepsy, Alzheimer Disease, Epilepsy Intractable
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
NPT 2042 (bumetanide analog) or Matching Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Epilepsy focused on measuring CNS Disorder, Seizure Disorder
Eligibility Criteria
Inclusion Criteria:
- Body mass index (BMI) of 18 to 32 kg/m2, inclusive
- A minimum body weight of 50 kg for males and 45 kg for females
- All females must have a negative serum pregnancy test at Screening and a negative serum pregnancy test upon admission to the clinical research center.
- Females must be of nonchild-bearing potential defined as permanently sterile (i.e., due to hysterectomy) or postmenopausal (defined as more than one year since last menstrual period).
- Male subjects with female partners of reproductive potential must agree to practice abstinence or to use a condom (male subjects) plus an additional barrier method (female partner) of contraception for the duration of the study and for at least 90 days after dosing; subjects must also agree to refrain from sperm donation for at least 90 days after their last dose of IP.
- Able to swallow capsules.
Exclusion Criteria:
- Presence of active or recurring clinically-significant cardiovascular, pulmonary, renal, endocrine, hepatic, neurologic, psychiatric, immunologic, hematologic, gastrointestinal, or metabolic disease requiring medical treatment.
- Presence of an active malignancy or a malignancy of any type within the past five years, other than squamous cell or basal cell carcinoma of the skin.
- Personal or family history of long QT syndrome.
- History or evidence of adverse symptoms associated with phlebotomy or blood donation (e.g., prolonged bleeding after injury or shaving, frequent epistaxis or gingival bleeding, bruises easily).
- History of clinically significant vertigo, dizziness or orthostatic hypotension or any vasovagal syncope or recurrent presyncope in connection with orthostatic challenge.
Reported use of or inability to refrain from or anticipated use of during the study
- any prescription drug within 14 days prior to dosing;
- any nonprescription drug, nutritional supplement, or vitamin within 7 days prior to dosing; NOTE: acetaminophen is allowed at a dose of ≤2000 mg/day
- any known enzyme-inducer or enzyme-inhibitor including St. John's Wort within 28 days prior to dosing, or
- reported chronic exposure to enzyme inducers such as paint solvents or pesticides within 30 days of dosing.
- Supine blood pressure (BP) less than 80/50 mmHg or greater than 140/90 mmHg.
- Supine heart rate <40 bpm and >90 bpm.
- History of drug abuse or current use of drugs of abuse or excessive ethanol intake
- Current Smoking, vaping, hookah, chewing tobacco, or history of smoking/vaping/chewing any substance
- Average consumption of ≥3 caffeine-containing beverages or xanthine-containing foods per day.
- Positive urine drug, alcohol, or cotinine result at screening
Sites / Locations
- Celerion
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Part A; Cohort 1
Part A; Cohort 2
Part A; Cohort 3
Part B; Cohort 1
Part B; Cohort 2
Part B; Cohort 3
Arm Description
QD dosing of 10mg (1 day)
QD dosing of 50mg (1 day)
QD dosing of 160mg (1 day)
Every 12-hour dosing of 20mg (7 days)
Every 12-hour dosing of 40mg (7 days)
Every 12-hour dosing of 80mg (7 days)
Outcomes
Primary Outcome Measures
Number of participants with adverse events
Absolute values and change from baseline after a single dose or after 7 days of repeated dosing.
Number of participants with abnormal lab test results
Absolute values and change from baseline after a single dose or after 7 days of repeated dosing in clinical chemistry, hematology, and urinalysis.
Number of participants with abnormal vital signs
Absolute values and change from baseline after a single dose or after 7 days of repeated dosing in vital signs (oral body temperature, respiratory rate, blood pressure, and heart rate).
Number of participants with abnormal ECG
Absolute values and change from baseline after a single dose or after 7 days of ECG intervals.
Secondary Outcome Measures
Pharmacokinetic Cmax
Maximum (peak) observed concentration of NPT 2042.
Pharmacokinetic Tmax
Time to maximum observed concentrations of NPT 2042.
Pharmacokinetic half-life (t1/2)
Time to terminal elimination half-life concentrations of NPT 2042.
Pharmacokinetic AUClast
Area under the concentration-time curve from zero to the last concentration quantifiable for NPT 2042.
Pharmacokinetic AUCinf
Area under the plasma concentration-time curve from time zero extrapolated to infinity for NPT 2042.
Pharmacokinetic CL/F
Apparent total plasma clearance after oral administration of NPT 2042.
Pharmacokinetic VzF
Apparent volume of distribution during terminal elimination phase after oral administration of NPT 2042.
Dose proportionality
Dose proportionality of NPT 2042 will be assessed using the power model.
Full Information
NCT ID
NCT05503511
First Posted
July 28, 2022
Last Updated
April 3, 2023
Sponsor
NeuroPro Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05503511
Brief Title
Safety and Pharmacokinetic Study of NPT 2042 Soft-gelatin Capsules Administered Orally to Healthy Adult Subjects
Official Title
A Single-center, Randomized, Placebo Controlled, Double-blind, Ascending Single-dose and Repeated-dose Trial to Determine the Safety and Pharmacokinetic Profile of NPT 2042 Soft-Gelatin Capsules Administered Orally to Healthy Adult Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
October 20, 2022 (Actual)
Primary Completion Date
March 17, 2023 (Actual)
Study Completion Date
March 30, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NeuroPro Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Study NPT 2042 CL 101 is a first in human (FIH) study to evaluate the safety and pharmacokinetics (PK) of single and repeated ascending doses of NPT 2042 in healthy adult male and female subjects.
Detailed Description
The long-term goal of this program is to develop NPT 2042 an adjunct antiseizure treatment for patients with medically intractable epilepsy. Prior to evaluating efficacy in the intended patient population, safety and pharmacokinetics of NPT 2042 will be investigated.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epilepsy, Alzheimer Disease, Epilepsy Intractable
Keywords
CNS Disorder, Seizure Disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part A; Cohort 1
Arm Type
Experimental
Arm Description
QD dosing of 10mg (1 day)
Arm Title
Part A; Cohort 2
Arm Type
Experimental
Arm Description
QD dosing of 50mg (1 day)
Arm Title
Part A; Cohort 3
Arm Type
Experimental
Arm Description
QD dosing of 160mg (1 day)
Arm Title
Part B; Cohort 1
Arm Type
Experimental
Arm Description
Every 12-hour dosing of 20mg (7 days)
Arm Title
Part B; Cohort 2
Arm Type
Experimental
Arm Description
Every 12-hour dosing of 40mg (7 days)
Arm Title
Part B; Cohort 3
Arm Type
Experimental
Arm Description
Every 12-hour dosing of 80mg (7 days)
Intervention Type
Drug
Intervention Name(s)
NPT 2042 (bumetanide analog) or Matching Placebo
Intervention Description
Soft gelatin capsules
Primary Outcome Measure Information:
Title
Number of participants with adverse events
Description
Absolute values and change from baseline after a single dose or after 7 days of repeated dosing.
Time Frame
Up to 11 days
Title
Number of participants with abnormal lab test results
Description
Absolute values and change from baseline after a single dose or after 7 days of repeated dosing in clinical chemistry, hematology, and urinalysis.
Time Frame
Up to 11 days
Title
Number of participants with abnormal vital signs
Description
Absolute values and change from baseline after a single dose or after 7 days of repeated dosing in vital signs (oral body temperature, respiratory rate, blood pressure, and heart rate).
Time Frame
Up to 11 days
Title
Number of participants with abnormal ECG
Description
Absolute values and change from baseline after a single dose or after 7 days of ECG intervals.
Time Frame
Up to 7 days
Secondary Outcome Measure Information:
Title
Pharmacokinetic Cmax
Description
Maximum (peak) observed concentration of NPT 2042.
Time Frame
0 (predose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 30, and 36 hours postdose
Title
Pharmacokinetic Tmax
Description
Time to maximum observed concentrations of NPT 2042.
Time Frame
0 (predose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 30, and 36 hours postdose
Title
Pharmacokinetic half-life (t1/2)
Description
Time to terminal elimination half-life concentrations of NPT 2042.
Time Frame
0 (predose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 30, and 36 hours postdose
Title
Pharmacokinetic AUClast
Description
Area under the concentration-time curve from zero to the last concentration quantifiable for NPT 2042.
Time Frame
0 (predose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 30, and 36 hours postdose
Title
Pharmacokinetic AUCinf
Description
Area under the plasma concentration-time curve from time zero extrapolated to infinity for NPT 2042.
Time Frame
0 (predose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 30, and 36 hours postdose
Title
Pharmacokinetic CL/F
Description
Apparent total plasma clearance after oral administration of NPT 2042.
Time Frame
0 (predose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 30, and 36 hours postdose
Title
Pharmacokinetic VzF
Description
Apparent volume of distribution during terminal elimination phase after oral administration of NPT 2042.
Time Frame
0 (predose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 30, and 36 hours postdose
Title
Dose proportionality
Description
Dose proportionality of NPT 2042 will be assessed using the power model.
Time Frame
0 (predose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 30, and 36 hours postdose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Body mass index (BMI) of 18 to 32 kg/m2, inclusive
A minimum body weight of 50 kg for males and 45 kg for females
All females must have a negative serum pregnancy test at Screening and a negative serum pregnancy test upon admission to the clinical research center.
Females must be of nonchild-bearing potential defined as permanently sterile (i.e., due to hysterectomy) or postmenopausal (defined as more than one year since last menstrual period).
Male subjects with female partners of reproductive potential must agree to practice abstinence or to use a condom (male subjects) plus an additional barrier method (female partner) of contraception for the duration of the study and for at least 90 days after dosing; subjects must also agree to refrain from sperm donation for at least 90 days after their last dose of IP.
Able to swallow capsules.
Exclusion Criteria:
Presence of active or recurring clinically-significant cardiovascular, pulmonary, renal, endocrine, hepatic, neurologic, psychiatric, immunologic, hematologic, gastrointestinal, or metabolic disease requiring medical treatment.
Presence of an active malignancy or a malignancy of any type within the past five years, other than squamous cell or basal cell carcinoma of the skin.
Personal or family history of long QT syndrome.
History or evidence of adverse symptoms associated with phlebotomy or blood donation (e.g., prolonged bleeding after injury or shaving, frequent epistaxis or gingival bleeding, bruises easily).
History of clinically significant vertigo, dizziness or orthostatic hypotension or any vasovagal syncope or recurrent presyncope in connection with orthostatic challenge.
Reported use of or inability to refrain from or anticipated use of during the study
any prescription drug within 14 days prior to dosing;
any nonprescription drug, nutritional supplement, or vitamin within 7 days prior to dosing; NOTE: acetaminophen is allowed at a dose of ≤2000 mg/day
any known enzyme-inducer or enzyme-inhibitor including St. John's Wort within 28 days prior to dosing, or
reported chronic exposure to enzyme inducers such as paint solvents or pesticides within 30 days of dosing.
Supine blood pressure (BP) less than 80/50 mmHg or greater than 140/90 mmHg.
Supine heart rate <40 bpm and >90 bpm.
History of drug abuse or current use of drugs of abuse or excessive ethanol intake
Current Smoking, vaping, hookah, chewing tobacco, or history of smoking/vaping/chewing any substance
Average consumption of ≥3 caffeine-containing beverages or xanthine-containing foods per day.
Positive urine drug, alcohol, or cotinine result at screening
Facility Information:
Facility Name
Celerion
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68502
Country
United States
12. IPD Sharing Statement
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Safety and Pharmacokinetic Study of NPT 2042 Soft-gelatin Capsules Administered Orally to Healthy Adult Subjects
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