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

A First in Human, Single Center, Single Dose, Randomized, Placebo-controlled, Dose, Escalating Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneously Administered ENT-03S for the Treatment of Obesity and Diabetes

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: ENT-03; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 91911
      • ProSciento

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Subjects aged 18-70 years, both genders.
2. Healthy as determined by a physician, based on history, medical examination, vital signs, and laboratory tests.
3. Males that agree to use condoms for the duration of participation in the study.
4. Females of non-child-bearing potential (i.e., tubal ligation, hysterectomy, or postmenopausal).
5. Female patients of child-bearing potential with negative serum pregnancy tests and who agree to use double-barrier contraception during the study.
6. 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.
7. Subjects must have a BMI 30-35 kg/m2 inclusive assessed immediately prior to screening.
8. Fasting insulin level ≥11 mIU/L.
9. HbA1c < 8.5% (diabetic subjects only).
10. Subjects with Type 2 diabetes on no anti-diabetic medication or on stable doses of metformin for 4 weeks or more (diabetic cohorts only).
11. 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).

Exclusion Criteria:

1. 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.
2. Pregnant or breastfeeding within six months of screening assessment.
3. Substantial changes in eating habits or exercise routine within the preceding three months.
4. Evidence of eating disorders.
5. >5% weight change in the past three months.
6. Bariatric surgery within the past five years.
7. Significant renal impairment (eGFR <60 mg/mL/1.73m2).
8. Patients on anti-diabetic medications other than metformin.
9. Patients with gastroparesis.
10. Liver function tests (i.e., ALT, AST, alkaline phosphatase) greater than twice the upper limit of normal upon repeated measurements.
11. Diseases interfering with metabolism and/or ingestive behavior (e.g., myxedema, Cushing's disease, schizophrenia, major psychoses).
12. 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.
13. Score of >15 on the Columbia Suicide Severity Rating Scale (C-SSRS).

14. Use of medications affecting body weight within the past three months:

    • Drugs approved for the treatment of obesity
    • Cyproheptadine or medroxyprogesterone
    • Atypical anti-psychotic drugs
    • Tricyclic antidepressants
    • Lithium, MAO's, glucocorticoids
    • SSRI's or SNRI's
    • Antiepileptic drugs
15. Any clinically significant abnormality following the Investigator's review of the physical examination and clinical laboratory tests.
16. A baseline prolongation of QT/QTc interval after repeated measurements of >450 ms; a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease, or a family history of Long QT Syndrome (LQTS).
17. Participation in an investigational drug trial within the month prior to dosing in the present study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active; Receive a single dose of ENT-03 sub-cutaneously	Drug: ENT-03; single dose of active drug
Placebo Comparator: Placebo; Receive a single dose of placebo sub-cutaneously	Drug: Placebo; single dose of placebo comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Endpoints: Maximum Plasma Concentration	maximum measured 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)	area under the concentration versus time curve over 24 hours	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	time required for drug concentration to decrease to 50% of maximum concentration	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	Body weight (kg) was measured at baseline (last measurement prior to first dose administration on Day 1) and at 168 hours post-dose (Day 8, End of Study). Change from baseline was calculated as the Day 8 value minus the baseline value.	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	Fasting leptin (ng/mL) was measured at baseline (last measurement prior to first dose administration on Day 1) and at post-dose visits. For Cohorts 1-3, assessments were performed at 24 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), and 168 hours post-dose (Day 8, End of Study). For Cohorts 4-7, assessments were performed at 72 hours (Day 4) and 168 hours post-dose (Day 8, End of Study) only. Change from baseline was calculated as the visit value minus the baseline value.	Baseline (pre-dose Day 1) and Day 8 (168 hours post-dose, End of Study)
Pharmacodynamic Endpoint: Change in Fasting Plasma Glucose From Baseline to Day 8	Fasting plasma glucose (mg/dL) was measured at baseline (last measurement prior to first dose administration on Day 1) and at post-dose visits. For Cohorts 1-3, assessments were performed at 24 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), and 168 hours post-dose (Day 8, End of Study). For Cohorts 4-7, assessments were performed at 72 hours (Day 4) and 168 hours post-dose (Day 8, End of Study) only. Change from baseline was calculated as the visit value minus the baseline value.	Baseline (pre-dose Day 1) and Day 8 (168 hours post-dose, End of Study)
Pharmacodynamic Endpoint: Change in Fasting Serum Insulin From Baseline to Day 8	Fasting serum insulin (μIU/mL) was measured at baseline (last measurement prior to first dose administration on Day 1) and at post-dose visits. For Cohorts 1-3, assessments were performed at 24 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), and 168 hours post-dose (Day 8, End of Study). For Cohorts 4-7, assessments were performed at 72 hours (Day 4) and 168 hours post-dose (Day 8, End of Study) only. Change from baseline was calculated as the visit value minus the baseline value.	Baseline (pre-dose Day 1) and Day 8 (168 hours post-dose, End of Study)

Collaborators and Investigators

• Sponsor: Metabolics Pharma
• Investigators: Study Director: Richard Larson, MD, Enterin Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2023
• Primary Completion (Actual): August 12, 2024
• Study Completion (Actual): August 12, 2024

Study Registration Dates

• First Submitted: June 5, 2023
• First Submitted That Met QC Criteria: June 22, 2023
• First Posted (Actual): June 29, 2023

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Diabetes Mellitus; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Diabetes Mellitus, Type 2
• Other Study ID Numbers: ENT-03S-22-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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