Diabetes Mellitus, Type 2, Obesity
Conditions
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.
Interventions
DRUGENT-03
single dose of active drug
DRUGPlacebo
single dose of placebo comparator
Sponsors
Metabolics Pharma
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 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. |
| Safety and Tolerability of ENT-03 | 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
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Endpoints: Maximum 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. | maximum measured plasma concentration |
| Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours Post-Dose (AUC₀-₂₄) | 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 |
| Pharmacokinetic Endpoint: Half-life | 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 |
| Change in Body Weight From Baseline to Day 8 | 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. |
| Pharmacodynamic Endpoint: Change in Fasting Leptin From Baseline to Day 8 | 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. |
| Pharmacodynamic Endpoint: Change in Fasting Plasma Glucose From Baseline to Day 8 | 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. |
| Pharmacodynamic Endpoint: Change in Fasting Serum Insulin From Baseline to Day 8 | 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. |
Countries
United States
Contacts
STUDY_DIRECTORRichard Larson, MD
Enterin Inc.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 54.0 years STANDARD_DEVIATION 10.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 14 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 14 |
| other Total, other adverse events | 1 / 5 | 2 / 5 | 5 / 5 | 4 / 5 | 4 / 5 | 4 / 5 | 3 / 5 | 3 / 14 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 14 |
Outcome results
None listed