Study of Subcutaneously Administered ENT-03 for the Treatment of Obesity and Diabetes

NCT05925920 | Completed Phase 1 Results FDA Drug

• 1 other identifier: ENT-03S-22-001
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

Single center, single-dose, randomized, placebo-controlled, dose-escalating study to evaluate, safety, tolerability, pharmacokinetics, and pharmacodynamics of escalating doses of ENT-03S in obese but otherwise healthy subjects and in subjects with obesity and Type 2 diabetes.

Conditions

Obesity; Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  Treatment Emergent Adverse events (TEAEs) were collected from Day 1 (dosing visit ) through End of Study visit (Day 14 post-dose). TEAEs were defined as any AE with onset on or after the date of study drug administration. TEAEs were recorded by the investigator based on subject report, clinical observation, physical examination, vital signs, laboratory assessments, and ECG findings. Severity was graded per NCI CTCAE v5.0. Relatedness to study drug was assessed by the investigator. TEAEs of special interest included nausea, vomiting, and injection site reactions.

  From Day 1 (dosing visit) through Day 14 (End of Study visit), approximately 3 to 4 weeks

• Safety and Tolerability of ENT-03

  QTcF (Fridericia-corrected QT interval) was assessed via 12-lead resting ECG at baseline (pre-dose Day 1) and at 72 hours post-dose (Day 4) and 168 hours post-dose (Day 8, End of Study).

  Baseline (pre-dose Day 1), Day 4 (72 hours post-dose), and Day 8 (168 hours post-dose, End of Study)

Secondary Outcomes (7)

• Pharmacokinetic Endpoints: Maximum Plasma Concentration

  Pre-dose (0 hours) and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose. Note: Cohorts 1 and 2 had samples collected through 72 hours; Cohort 3 through 120 hours; Cohorts 4-7 through 168 hours.

• Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours Post-Dose (AUC₀-₂₄)

  0, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose (Cohorts 3-7); 0, 1, 2, 4, 8, 12, and 24 hours post-dose (Cohorts 1-2)

• Pharmacokinetic Endpoint: Half-life

  Sampling through 72 hours post-dose (Cohorts 1-2), 120 hours (Cohort 3), and 168 hours (Cohorts 4-7).

• Change in Body Weight From Baseline to Day 8

  Baseline (pre-dose Day 1) and Day 8 (168 hours post-dose, End of Study)

• Pharmacodynamic Endpoint: Change in Fasting Leptin From Baseline to Day 8

  Baseline (pre-dose Day 1) and Day 8 (168 hours post-dose, End of Study)

Study Arms (2)

Active

ACTIVE COMPARATOR

Receive a single dose of ENT-03 sub-cutaneously

Drug: ENT-03

Placebo

PLACEBO COMPARATOR

Receive a single dose of placebo sub-cutaneously

Drug: Placebo

Interventions

ENT-03 DRUG

single dose of active drug

Active

Placebo DRUG

single dose of placebo comparator

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects aged 18-70 years, both genders.
• Healthy as determined by a physician, based on history, medical examination, vital signs, and laboratory tests.
• Males that agree to use condoms for the duration of participation in the study.
• Females of non-child-bearing potential (i.e., tubal ligation, hysterectomy, or postmenopausal).
• Female patients of child-bearing potential with negative serum pregnancy tests and who agree to use double-barrier contraception during the study.
• Subjects must be able to read, speak, and understand English and/or Spanish and provide written informed consent, and be willing and able to comply with study procedures.
• Subjects must have a BMI 30-35 kg/m2 inclusive assessed immediately prior to screening.
• Fasting insulin level ≥11 mIU/L.
• HbA1c \< 8.5% (diabetic subjects only).
• Subjects with Type 2 diabetes on no anti-diabetic medication or on stable doses of metformin for 4 weeks or more (diabetic cohorts only).
• No history of active or chronic disease other than that allowed by study: hypertension, hyperlipidemia, hyperglycemia, GERD, heartburn, or Type 2 diabetes (cohorts 6 and 7 only).

You may not qualify if:

• History of excessive alcohol use (defined as \>21 drinks per week for males and \>14 drinks per week for females), recreational drug use within the past three months, or failure on urinary drug screen.
• Pregnant or breastfeeding within six months of screening assessment.
• Substantial changes in eating habits or exercise routine within the preceding three months.
• Evidence of eating disorders.
• \>5% weight change in the past three months.
• Bariatric surgery within the past five years.
• Significant renal impairment (eGFR \<60 mg/mL/1.73m2).
• Patients on anti-diabetic medications other than metformin.
• Patients with gastroparesis.
• Liver function tests (i.e., ALT, AST, alkaline phosphatase) greater than twice the upper limit of normal upon repeated measurements.
• Diseases interfering with metabolism and/or ingestive behavior (e.g., myxedema, Cushing's disease, schizophrenia, major psychoses).
• History of major depressive disorder within the previous two years, a lifetime history of suicide attempt, suicidal behavior within the previous month, or history of other severe psychiatric disorders.
• Score of \>15 on the Columbia Suicide Severity Rating Scale (C-SSRS).
• Use of medications affecting body weight within the past three months:
• Drugs approved for the treatment of obesity

Sponsors & Collaborators

• Metabolics Pharma: lead

Study Sites (1)

ProSciento

San Diego, California, 91911, United States

Location

MeSH Terms

Conditions

Obesity; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Richard Larson, MD
• Organization: MetabolicsPharma

r.larson@metabolicspharma.com

NA

Study Officials

• Richard Larson, MD

  Enterin Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: June 5, 2023
• First Posted: June 29, 2023
• Study Start: June 13, 2023
• Primary Completion: August 12, 2024
• Study Completion: August 12, 2024
• Last Updated: June 1, 2026
• Results First Posted: June 1, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)