Safety and Pharmacokinetic Study of NPT 2042 Soft-gelatin Capsules Administered Orally to Healthy Adult Subjects

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 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.

Study Overview

• Status: Completed
• Conditions: Epilepsy; Alzheimer Disease; Epilepsy Intractable
• Intervention / Treatment: Drug: NPT 2042 (bumetanide analog) or Matching Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Daryl Hochman; Phone Number: (919) 812-0485; Email: daryl@npt.io

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Body mass index (BMI) of 18 to 32 kg/m2, inclusive
2. A minimum body weight of 50 kg for males and 45 kg for females
3. All females must have a negative serum pregnancy test at Screening and a negative serum pregnancy test upon admission to the clinical research center.
4. 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).
5. 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.
6. Able to swallow capsules.

Exclusion Criteria:

1. Presence of active or recurring clinically-significant cardiovascular, pulmonary, renal, endocrine, hepatic, neurologic, psychiatric, immunologic, hematologic, gastrointestinal, or metabolic disease requiring medical treatment.
2. 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.
3. Personal or family history of long QT syndrome.
4. 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).
5. History of clinically significant vertigo, dizziness or orthostatic hypotension or any vasovagal syncope or recurrent presyncope in connection with orthostatic challenge.

6. 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.
7. Supine blood pressure (BP) less than 80/50 mmHg or greater than 140/90 mmHg.
8. Supine heart rate <40 bpm and >90 bpm.
9. History of drug abuse or current use of drugs of abuse or excessive ethanol intake
10. Current Smoking, vaping, hookah, chewing tobacco, or history of smoking/vaping/chewing any substance
11. Average consumption of ≥3 caffeine-containing beverages or xanthine-containing foods per day.
12. Positive urine drug, alcohol, or cotinine result at screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A; Cohort 1; QD dosing of 10mg (1 day)	Drug: NPT 2042 (bumetanide analog) or Matching Placebo; Soft gelatin capsules
Experimental: Part A; Cohort 2; QD dosing of 50mg (1 day)	Drug: NPT 2042 (bumetanide analog) or Matching Placebo; Soft gelatin capsules
Experimental: Part A; Cohort 3; QD dosing of 160mg (1 day)	Drug: NPT 2042 (bumetanide analog) or Matching Placebo; Soft gelatin capsules
Experimental: Part B; Cohort 1; Every 12-hour dosing of 20mg (7 days)	Drug: NPT 2042 (bumetanide analog) or Matching Placebo; Soft gelatin capsules
Experimental: Part B; Cohort 2; Every 12-hour dosing of 40mg (7 days)	Drug: NPT 2042 (bumetanide analog) or Matching Placebo; Soft gelatin capsules
Experimental: Part B; Cohort 3; Every 12-hour dosing of 80mg (7 days)	Drug: NPT 2042 (bumetanide analog) or Matching Placebo; Soft gelatin capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events	Absolute values and change from baseline after a single dose or after 7 days of repeated dosing.	Up to 11 days
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.	Up to 11 days
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).	Up to 11 days
Number of participants with abnormal ECG	Absolute values and change from baseline after a single dose or after 7 days of ECG intervals.	Up to 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Cmax	Maximum (peak) observed concentration of NPT 2042.	0 (predose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 30, and 36 hours postdose
Pharmacokinetic Tmax	Time to maximum observed concentrations of NPT 2042.	0 (predose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 30, and 36 hours postdose
Pharmacokinetic half-life (t1/2)	Time to terminal elimination half-life concentrations of NPT 2042.	0 (predose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 30, and 36 hours postdose
Pharmacokinetic AUClast	Area under the concentration-time curve from zero to the last concentration quantifiable for NPT 2042.	0 (predose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 30, and 36 hours postdose
Pharmacokinetic AUCinf	Area under the plasma concentration-time curve from time zero extrapolated to infinity for NPT 2042.	0 (predose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 30, and 36 hours postdose
Pharmacokinetic CL/F	Apparent total plasma clearance after oral administration of NPT 2042.	0 (predose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 30, and 36 hours postdose
Pharmacokinetic VzF	Apparent volume of distribution during terminal elimination phase after oral administration of NPT 2042.	0 (predose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 30, and 36 hours postdose
Dose proportionality	Dose proportionality of NPT 2042 will be assessed using the power model.	0 (predose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 30, and 36 hours postdose

Collaborators and Investigators

• Sponsor: NeuroPro Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2022
• Primary Completion (Actual): March 17, 2023
• Study Completion (Actual): March 30, 2023

Study Registration Dates

• First Submitted: July 28, 2022
• First Submitted That Met QC Criteria: August 12, 2022
• First Posted (Actual): August 16, 2022

Study Record Updates

• Last Update Posted (Actual): April 4, 2023
• Last Update Submitted That Met QC Criteria: April 3, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Seizure Disorder; CNS Disorder
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Epilepsy; Alzheimer Disease; Drug Resistant Epilepsy; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Bumetanide
• Other Study ID Numbers: NPT 2042 CL-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No