A Study to Assess Safety, Tolerability and Exposure of 4ET1103 in Healthy Human Volunteers

NCT07586514 | Completed Phase 1 FDA Drug

• 2 other identifiers: 4ET1103-001U44NS115692
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This study will dose healthy human volunteers with either active drug (4ET1103) or placebo. Each study subject will receive a single dose of either active drug or placebo, and will then be monitored for safety, tolerability and exposure of active drug.

Conditions

Neuropathic Pain

Outcome Measures

Primary Outcomes (7)

• Change from baseline in hematology parameters

  Hematology laboratory parameters (for example, complete blood count including erythrocytes, leukocytes with differential, hemoglobin, hematocrit, and platelets) will be summarized as observed values and changes from baseline at each postdose time point, and the number of subjects with clinically significant abnormalities will be reported.

  14 days

• Change from baseline in serum chemistry parameters

  Serum chemistry laboratory parameters (for example, electrolytes, liver function tests, renal function tests, and lipids) will be summarized as observed values and changes from baseline at each post dose time point, and the number of subjects with clinically significant abnormalities will be reported.

  14 days

• Change from baseline in urinalysis parameters.

  Urinalysis parameters (for example, urine specific gravity, pH, protein, glucose, ketones, blood/occult blood, nitrite, leukocyte esterase, and bilirubin) will be summarized as observed values and changes from baseline at each post dose time point, and the number of subjects with clinically significant abnormalities will be reported

  14 days

• Change from baseline in coagulation parameters

  Coagulation parameters (for example, prothrombin time, international normalized ratio, and activated partial thromboplastin time) will be summarized as observed values and changes from baseline at each post dose time point, and the number of subjects with clinically significant abnormalities will be reported.

  14 days

• Change from bassline in vital signs

  Vital signs, including systolic and diastolic blood pressure, pulse rate, respiratory rate, and body temperature, will be summarized as observed values and changes from baseline at each postdose time point, and the number of subjects with clinically significant abnormalities will be reported.

  14 days

• Change from baseline in 12-lead ECG parameters

  Twelve-lead ECG parameters (for example, heart rate, PR interval, QRS duration, QT interval, and QTc) will be summarized as observed values and changes from baseline at each post dose time point, and the number of subjects with clinically significant ECG abnormalities will be reported.

  14 days

• Incidence of treatment-emergent adverse events (TEAEs)

  The number of subjects with treatment-emergent adverse events (TEAEs), including serious and non-serious AEs, will be summarized by system organ class and preferred term, severity, and relationship to study drug from first dose through the end of safety follow-up

  72 hours

Secondary Outcomes (9)

• Drug excreted in urine (Ae) to be determined.

  24 hours after single dose 4ET1103

• Peak Plasma Concentration (Cmax)

  PK measurements will be followed for out to 7 days from single dose of 4ET1103

• Renal clearance (CLR) will be measured.

  24 hours following single dose of 4ET1103

• Fraction of dose excreted renally (Fe)

  24 hours following single dose of 4ET1103

• Area under the plasma concentration versus time curve (AUC)

  PK measurements out to 7 days following single dose of 4ET1103

Other Outcomes (1)

• The change from baseline in the levels of p-eIF4E will be assessed in whole blood at specified timepoints

  Out to 7 days post dose 4ET1103

Study Arms (10)

Cohort 1 active

EXPERIMENTAL

45 mg active

Drug: Treatment for neuropathic pain

Cohort 1 placebo

PLACEBO COMPARATOR

placebo for 45 mg

Drug: placebo

Cohort 2 active

EXPERIMENTAL

135 mg 4ET1103

Drug: Treatment for neuropathic pain

Cohort 2 placebo

PLACEBO COMPARATOR

placebo for 135 mg

Drug: placebo

Cohort 3 active

EXPERIMENTAL

270 mg 4ET1103

Drug: Treatment for neuropathic pain

Cohort 3 placebo

PLACEBO COMPARATOR

placebo for 270 mg

Drug: placebo

Cohort 4 active

EXPERIMENTAL

450 mg 4ET1103

Drug: Treatment for neuropathic pain

Cohort 4 placebo

PLACEBO COMPARATOR

placebo for 450 mg

Drug: placebo

cohort 5 active

EXPERIMENTAL

720 mg 4ET1103

Drug: Treatment for neuropathic pain

cohort 5 placebo

PLACEBO COMPARATOR

placebo for 720 mg

Drug: placebo

Interventions

Treatment for neuropathic pain DRUG

MNK inhibitor for treatment of neuropathic pain

Cohort 1 active; Cohort 2 active; Cohort 3 active; Cohort 4 active; cohort 5 active

placebo DRUG

placebo for MNK inhibitor

Cohort 1 placebo; Cohort 2 placebo; Cohort 3 placebo; Cohort 4 placebo; cohort 5 placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Gender Eligibility Details: males and females based on sex at birth
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy males and females (sex at birth) between 18 and 65 years of age; inclusive based on the date of Screening.
• Body mass index (BMI) between 18 and 32 kg/m2 (inclusive) and weigh at least 50 kg at Screening and Day -1.
• Provision of signed and dated, written informed consent prior to any study-specific procedures
• Female subjects have a negative serum pregnancy test result at Screening and negative urine pregnancy test result at Day -1.
• Female subjects with male partners must meet one of the following criteria:
• Using a medically acceptable form of birth control for at least 30 days prior to Screening (60 days on oral contraceptives) until 3 months following the last dose of study drug \[e.g., hormonal contraceptives (oral, patch, injectable or vaginal ring), implantable device (implantable rod or intrauterine device), bilateral tubal ligation/tubal occlusion or a double barrier (e.g., diaphragm, cervical cap, condom in conjunction with spermicide or sponge)\]. For female subjects using hormonal contraceptives, it is also required to use at least one additional form of contraception, i.e., implantable device (implantable rod or intrauterine device), or a double barrier method (e.g., diaphragm, cervical cap, or condom in conjunction with spermicide or sponge).
• Surgically sterile for at least 3 months prior to Screening by one of the following means:
• Bilateral salpingectomy (with or without oophorectomy)
• Surgical hysterectomy
• Bilateral oophorectomy (with or without hysterectomy) c. Postmenopausal, defined as the following:
• Female subjects with 12 months consecutive amenorrhea and follicle-stimulating hormone (FSH) levels greater than 40 international units per liter (IU/L) at Screening.
• d. Female subjects of reproductive potential who are abstinent of heterosexual activity (when in line with the preferred and usual lifestyle of the subject), are acceptable provided they agree to a double barrier method for at least 3 months after their last dose of the study drug should they become sexually active with a male partner.
• e. Females must agree to avoid egg donation throughout the study and for at least 3 months after last dose of study drug.
• Male subjects with female partners have history of vasectomy or must agree to utilize a highly effective method of contraception (condom with spermicide) during heterosexual intercourse from clinic admission until at least 3 months following the last dose of the study drug and must refrain from donating sperm for this same period.
• Considered healthy by the Investigator, based on subject's reported medical history, full physical examination, clinical laboratory tests, 12-lead ECG, and vital signs at Screening and Day -1.

You may not qualify if:

• History or presence of any illness, condition, or finding that in the opinion of the Principal Investigator (PI) or designee would put the subject or study conduct at risk, or have the potential to confound the results of the study, if the subject were to participate in the study.
• History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, bleeding disorder or psychiatric disease or drug hypersensitivity as determined by the Investigator
• In opinion of the Investigator, the subject has history of any true drug allergy; excluding histories limited to mild to moderate gastrointestinal distress (nausea, anorexia, diarrhea, infrequent vomiting).
• History of alcohol abuse (drinking 14 units of alcohol per week: 1 unit = 360 mL of beer, or 37 mL of spirits, or 120 mL of wine) within 3 months prior to Screening, or positive urine alcohol test at Screening or Day -1. Subjects must agree to abstain from alcohol intake from 72 hours before study drug administration through discharge from the CRU.
• History of prescription drug abuse, or marijuana or cannabis product use or illicit drug use within 6 months prior to Screening, or positive findings on the urine drug screen at Screening or Day -1.
• History of organ transplant, including history of bone marrow transplant.
• Use of any prescription (excluding contraceptives) medication, over the counter (OTC) medication or herbal supplements within 7 days or 5 half-lives, whichever is longer prior to Day 1.
• Evidence of severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) infection or oral temperature \>38°C at Day -1. During the study, if subjects have infections, the subjects may continue the study at the discretion of the Investigator. In the case of COVID-19 infection, subject will be withdrawn.
• Subjects who have received any vaccines within 30 days prior to Day 1
• Donated or lost blood \>500 ml within 60 days prior to Screening
• Acute illness within 14 days of study Day 1; acute illness occurring before this must show complete recovery at least 14 days prior to Day 1.
• Regular consumption of \> 3caffeine - or xanthine-containing products in 2 weeks before Screening and unwilling to consume \<3 caffeine - or xanthine-containing products while confined at the CRU.
• Positive serologic findings for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody (Ab), and/or Human immunodeficiency virus (HIV) Ab at Screening.
• Positive Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening
• Surgery within the past 90 days prior to Day 1 as determined by the Investigator to be clinically relevant.

Sponsors & Collaborators

• 4E Therapeutics: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

PPD

Austin, Texas, 78744, United States

Location

MeSH Terms

Conditions

Neuralgia

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Kristie Miller, MD

  PPD Development, LP

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 22, 2026
• First Posted: May 14, 2026
• Study Start: April 18, 2025
• Primary Completion: August 18, 2025
• Study Completion: August 18, 2025
• Last Updated: May 14, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)