Clinical trial NCT05925920: Study of Subcutaneously Administered ENT-03 for the Treatment of Obesity and Diabetes
Official 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Obesity
Diabetes Mellitus, Type 2
Lead sponsor: Metabolics Pharma
Sponsor class: INDUSTRY
First posted: 2023-06-29
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Safety and tolerability of ENT-03
timeFrame: 7 days
measure: Safety and Tolerability of ENT-03
timeFrame: 7 days
measure: Safety and Tolerability of ENT-03
timeFrame: 7 days
measure: Safety and Tolerability of ENT-03
timeFrame: 7 days
measure: Safety and Tolerability of ENT-03
timeFrame: 7 days
measure: Safety and Tolerability of ENT-03
timeFrame: 7 days
measure: Safety and Tolerability of ENT-03
timeFrame: 7 days
measure: Safety and Tolerability of ENT-03
timeFrame: 7 days
Secondary outcomes:
measure: pharmacokinetic endpoints: maximum plasma concentration
timeFrame: pre-dose, 24 hours, 48 house, 72 hours
measure: pharmacokinetic endpoints: time of maximum plasma concentration
timeFrame: pre-dose, 24 hours, 48 house, 72 hours
measure: pharmacokinetic endpoints: ENT-03 half-life
timeFrame: pre-dose, 24 hours, 48 house, 72 hours
measure: pharmacokinetic endpoints: plasma concentration
timeFrame: pre-dose, 24 hours, 48 house, 72 hours
measure: pharmacokinetic endpoint: ENT-03 clearance
timeFrame: pre-dose, 24 hours, 48 house, 72 hours
measure: pharmacokinetic endpoint: elimination phase
timeFrame: pre-dose, 24 hours, 48 house, 72 hours
measure: pharmacodynamic endpoint: glucose
timeFrame: 7 days
measure: pharmacodynamic endpoint: insulin
timeFrame: 7 days
measure: pharmacodynamic endpoint: fasting lipids
timeFrame: 7 days
measure: pharmacodynamic endpoint: fasting leptin
timeFrame: 7 days
measure: pharmacodynamic endpoint: body weight
timeFrame: 7 days
measure: effect on glucose
timeFrame: Days -7, 2, 3, 4, and 7
measure: effect on insulin and insulin sensitivity
timeFrame: Days -7, 2, 3, 4, and 7
Other outcomes:
Locations:
city: San Diego
country: United States
facility: ProSciento
state: California
Study officials:
affiliation: Enterin Inc.
name: Richard Larson, MD
role: STUDY_DIRECTOR
References: