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

NCT05503511 | Completed Phase 1 FDA Drug

• 1 other identifier: NPT 2042 CL-101
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Epilepsy; Alzheimer Disease; Epilepsy Intractable

Keywords

CNS Disorder; Seizure Disorder

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (8)

• Pharmacokinetic Cmax

  0 (predose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 30, and 36 hours postdose

• Pharmacokinetic Tmax

  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)

  0 (predose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 30, and 36 hours postdose

• Pharmacokinetic AUClast

  0 (predose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 30, and 36 hours postdose

• Pharmacokinetic AUCinf

  0 (predose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 30, and 36 hours postdose

Study Arms (6)

Part A; Cohort 1

EXPERIMENTAL

QD dosing of 10mg (1 day)

Drug: NPT 2042 (bumetanide analog) or Matching Placebo

Part A; Cohort 2

EXPERIMENTAL

QD dosing of 50mg (1 day)

Drug: NPT 2042 (bumetanide analog) or Matching Placebo

Part A; Cohort 3

EXPERIMENTAL

QD dosing of 160mg (1 day)

Drug: NPT 2042 (bumetanide analog) or Matching Placebo

Part B; Cohort 1

EXPERIMENTAL

Every 12-hour dosing of 20mg (7 days)

Drug: NPT 2042 (bumetanide analog) or Matching Placebo

Part B; Cohort 2

EXPERIMENTAL

Every 12-hour dosing of 40mg (7 days)

Drug: NPT 2042 (bumetanide analog) or Matching Placebo

Part B; Cohort 3

EXPERIMENTAL

Every 12-hour dosing of 80mg (7 days)

Drug: NPT 2042 (bumetanide analog) or Matching Placebo

Interventions

NPT 2042 (bumetanide analog) or Matching Placebo DRUG

Soft gelatin capsules

Part A; Cohort 1; Part A; Cohort 2; Part A; Cohort 3; Part B; Cohort 1; Part B; Cohort 2; Part B; Cohort 3

Eligibility Criteria

• Age: 19 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• NeuroPro Therapeutics, Inc.: lead

Study Sites (1)

Celerion

Lincoln, Nebraska, 68502, United States

Location

MeSH Terms

Conditions

Epilepsy; Alzheimer Disease; Drug Resistant Epilepsy; Central Nervous System Diseases

Interventions

Bumetanide

Condition Hierarchy (Ancestors)

Brain Diseases; Nervous System Diseases; Dementia; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; meta-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2022
• First Posted: August 16, 2022
• Study Start: October 20, 2022
• Primary Completion: March 17, 2023
• Study Completion: March 30, 2023
• Last Updated: April 4, 2023

Record last verified: 2023-04

Locations

US (1)