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

Obesity Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05925920
• Other study ID #: ENT-03S-22-001
• Status: Recruiting
• Phase: Phase 1
• Start date: June 13, 2023
• Est. completion date: October 30, 2024

Study information

• Verified date: April 2024
• Source: Enterin Inc.
• Contact: Jennifer Beezley
• Phone: 866-308-7427
• Email: info[@]enterininc.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 49
• Est. completion date: October 30, 2024
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Obesity

Intervention

Drug:
• ENT-03
single dose of active drug
• Placebo
single dose of placebo comparator

Locations

Country	Name	City	State
United States	ProSciento	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Enterin Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of ENT-03	Adverse Events	7 days
Primary	Safety and Tolerability of ENT-03	ECG: QTc analysis	7 days
Primary	Safety and Tolerability of ENT-03	Vital signs: body temperature	7 days
Primary	Safety and Tolerability of ENT-03	Vital signs: respiration rate	7 days
Primary	Safety and Tolerability of ENT-03	Vital signs: heart rate	7 days
Primary	Safety and Tolerability of ENT-03	Vital signs: systolic blood pressure measurements	7 days
Primary	Safety and Tolerability of ENT-03	Vital signs: diastolic blood pressure measurements	7 days
Primary	Safety and Tolerability of ENT-03	Vital signs: body weight in kilograms	7 days
Secondary	pharmacokinetic endpoints: maximum plasma concentration	maximum measured plasma concentration	pre-dose, 24 hours, 48 house, 72 hours
Secondary	pharmacokinetic endpoints: time of maximum plasma concentration	time of maximum measured plasma concentration	pre-dose, 24 hours, 48 house, 72 hours
Secondary	pharmacokinetic endpoints: ENT-03 half-life	terminal elimination of ENT-03 half-life in plasma	pre-dose, 24 hours, 48 house, 72 hours
Secondary	pharmacokinetic endpoints: plasma concentration	area under the concentration versus time curve over 24 hours	pre-dose, 24 hours, 48 house, 72 hours
Secondary	pharmacokinetic endpoint: ENT-03 clearance	Clearance of ENT-03	pre-dose, 24 hours, 48 house, 72 hours
Secondary	pharmacokinetic endpoint: elimination phase	slope of terminal elimination phase	pre-dose, 24 hours, 48 house, 72 hours
Secondary	pharmacodynamic endpoint: glucose	change from screening visit in fasting plasma glucose	7 days
Secondary	pharmacodynamic endpoint: insulin	change from screening visit in fasting serum insulin	7 days
Secondary	pharmacodynamic endpoint: fasting lipids	change from screening visit in fasting lipids	7 days
Secondary	pharmacodynamic endpoint: fasting leptin	change from screening visit in fasting leptin	7 days
Secondary	pharmacodynamic endpoint: body weight	change from screening visit in body weight (kg)	7 days
Secondary	effect on glucose	results of fasting and post-prandial blood glucose in subjects with obesity and T2D	Days -7, 2, 3, 4, and 7
Secondary	effect on insulin and insulin sensitivity	results of fasting and post-prandial blood insulin and insulin sensitivity as measured by homeostatic assessment of insulin resistance (HOMAIR), in subjects with obesity and T2D	Days -7, 2, 3, 4, and 7