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Completed

NCT Number: NCT05925920

Study of Subcutaneously Administered ENT-03 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.

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Key information

Conditions

Obesity Body Weight Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutrition Disorders Nutritional and Metabolic Diseases Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

ProSciento

San Diego, California, 91911, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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).

Exclusion criteria

  • 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
  • Cyproheptadine or medroxyprogesterone
  • Atypical anti-psychotic drugs
  • Tricyclic antidepressants
  • Lithium, MAO's, glucocorticoids
  • SSRI's or SNRI's
  • Antiepileptic drugs
  • Any clinically significant abnormality following the Investigator's review of the physical examination and clinical laboratory tests.
  • 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).
  • Participation in an investigational drug trial within the month prior to dosing in the present study.

Treatment and study plan

ENT-03

Drug

single dose of active drug

Placebo

Drug

single dose of placebo comparator

Primary outcomes

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

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

    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.

  2. Safety and Tolerability of ENT-03

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

    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).

Secondary outcomes

  1. Pharmacokinetic Endpoints: Maximum Plasma Concentration

    Time frame: 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.

    maximum measured plasma concentration

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

    Time frame: 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)

    area under the concentration versus time curve over 24 hours

  3. Pharmacokinetic Endpoint: Half-life

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

    time required for drug concentration to decrease to 50% of maximum concentration

  4. Change in Body Weight From Baseline to Day 8

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

    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.

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

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

    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.

  6. Pharmacodynamic Endpoint: Change in Fasting Plasma Glucose From Baseline to Day 8

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

    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.

  7. Pharmacodynamic Endpoint: Change in Fasting Serum Insulin From Baseline to Day 8

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

    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.

Sponsors and collaborators

Lead sponsor

Metabolics Pharma

Industry

Registry information

Official study title

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

Important dates

Study start
2023
Primary completion
2024
Study completion
2024
First posted
Jun 29, 2023
Registry last updated
Jun 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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