Study of Subcutaneously Administered ENT-03 for the Treatment of Obesity and Diabetes
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- Safety and tolerability of ENT-03 [7 days]
Adverse Events
- Safety and Tolerability of ENT-03 [7 days]
ECG: QTc analysis
- Safety and Tolerability of ENT-03 [7 days]
Vital signs: body temperature
- Safety and Tolerability of ENT-03 [7 days]
Vital signs: respiration rate
- Safety and Tolerability of ENT-03 [7 days]
Vital signs: heart rate
- Safety and Tolerability of ENT-03 [7 days]
Vital signs: systolic blood pressure measurements
- Safety and Tolerability of ENT-03 [7 days]
Vital signs: diastolic blood pressure measurements
- Safety and Tolerability of ENT-03 [7 days]
Vital signs: body weight in kilograms
Secondary Outcome Measures
- pharmacokinetic endpoints: maximum plasma concentration [pre-dose, 24 hours, 48 house, 72 hours]
maximum measured plasma concentration
- pharmacokinetic endpoints: time of maximum plasma concentration [pre-dose, 24 hours, 48 house, 72 hours]
time of maximum measured plasma concentration
- pharmacokinetic endpoints: ENT-03 half-life [pre-dose, 24 hours, 48 house, 72 hours]
terminal elimination of ENT-03 half-life in plasma
- pharmacokinetic endpoints: plasma concentration [pre-dose, 24 hours, 48 house, 72 hours]
area under the concentration versus time curve over 24 hours
- pharmacokinetic endpoint: ENT-03 clearance [pre-dose, 24 hours, 48 house, 72 hours]
Clearance of ENT-03
- pharmacokinetic endpoint: elimination phase [pre-dose, 24 hours, 48 house, 72 hours]
slope of terminal elimination phase
- pharmacodynamic endpoint: glucose [7 days]
change from screening visit in fasting plasma glucose
- pharmacodynamic endpoint: insulin [7 days]
change from screening visit in fasting serum insulin
- pharmacodynamic endpoint: fasting lipids [7 days]
change from screening visit in fasting lipids
- pharmacodynamic endpoint: fasting leptin [7 days]
change from screening visit in fasting leptin
- pharmacodynamic endpoint: body weight [7 days]
change from screening visit in body weight (kg)
- effect on glucose [Days -7, 2, 3, 4, and 7]
results of fasting and post-prandial blood glucose in subjects with obesity and T2D
- effect on insulin and insulin sensitivity [Days -7, 2, 3, 4, and 7]
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
Eligibility Criteria
Criteria
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.
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Substantial changes in eating habits or exercise routine within the preceding three months.
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Evidence of eating disorders.
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5% weight change in the past three months.
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Bariatric surgery within the past five years.
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Significant renal impairment (eGFR <60 mg/mL/1.73m2).
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Patients on anti-diabetic medications other than metformin.
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Patients with gastroparesis.
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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).
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Use of medications affecting body weight within the past three months:
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Drugs approved for the treatment of obesity
-
Cyproheptadine or medroxyprogesterone
-
Atypical anti-psychotic drugs
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | ProSciento | San Diego | California | United States | 91911 |
Sponsors and Collaborators
- Enterin Inc.
Investigators
- Study Director: Denise Barbut, Enterin Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ENT-03S-22-001