Study to Evaluate Safety and Activity of TRL345 in Healthy Volunteers

Exclusion Criteria

• •1. Inability to tolerate blood draws or has poor venous access
• •2. Body mass index (BMI) \<18.5 or ≥35 kg/m2
• •3. Clinically significant vital sign abnormalities (systolic blood pressure lower than 90 or over 160 mmHg; diastolic blood pressure lower than 50 or over 100 mmHg; or, heart rate less than 45 or over 100 bpm) at the Screening Visit
• •4. ECG with clinically significant findings, including:
• •1. Conduction disturbance (complete left or complete right bundle branch block or nonspecific intraventricular conduction disturbance with QRS ≥120 msec, PR interval ≥220 msec, any second- or third-degree atrioventricular block, or prolongation of the QT interval corrected according to Fridericia's correction \[\>450 msec male and \>460 msec female\])
• •2. Significant repolarization (ST-segment or T-wave) abnormality; or
• •3. Significant atrial or ventricular arrhythmia; or
• •4. Frequent atrial or ventricular ectopy (e.g., frequent premature atrial contractions, 2 premature ventricular contractions in a row); or
• •5. ST-elevation consistent with ischemia or evidence of past or evolving myocardial infarction.
• •5. Presence of any gastrointestinal pathology (e.g., chronic diarrhea, inflammatory bowel diseases), unresolved gastrointestinal symptoms (e.g., diarrhea, vomiting),or progressive liver or kidney disease
• •6. Diagnosis of diabetes mellitus
• •7. History of acute or chronic pancreatitis or upper right quadrant postprandial discomfort or pain within the last 2 years
• •8. Clinically relevant medical conditions that, in the opinion of the PI, may interfere with the evaluation of the trial drug, e.g., progressive cardiovascular disease
• •9. Concurrent acute or chronic infections (e.g., viral infections, except chronic recurrent herpes simplex infections)
• •10. Significant abnormal safety labs, defined as:
• •* Greater than 30% outside of the normal range for any of the following: hemoglobin, white blood cell (WBC) count, platelet count, neutrophil count and blood urea nitrogen
• •* Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), direct bilirubin or indirect bilirubin \>2 × the upper limit of normal
• •* Activated partial thromboplastin time (aPTT) prolongation \>1.5 x ULN
• •* Hemoglobin A1C (HbA1C) \>5.6%
• •* Fasting glucose level of ≥100 mg/dl (5.6 mmol/L)
• •* Renal function based on the, i.e., estimated creatinine clearance \< 70 mL/min (Cockcroft-Gault formula using ideal body weight)
• •* Hemoglobin ≤ 128 g/L (males) and ≤ 115 g/L (females), and hematocrit ≤ 37% (males) and ≤ 32.0% for females
• •11. Positive test results for HIV, Hepatitis B (HBsAg), or Hepatitis C (HCV) at the Screening Visit
• •12. History of significant drug abuse within one year prior to the Screening Visit and/or ongoing
• •13. History of significant alcohol abuse within one year prior to the Screening Visit defined as more than fourteen units of alcohol per week \[one "unit" is equal to approximately ½ pint \[200 mL\] of beer, 1 small glass \[100 mL\] of wine, or 1 measure \[25 mL\] of spirits)
• •14. Positive test for drugs of abuse, ETOH and nicotine (cotinine) at the Screening Visit
• •15. Positive serum beta-human chorionic gonadotropin test for pregnancy, pregnant, or nursing women
• •16. Unwilling to refrain from donating blood or plasma during the study.
• •17. Use of any new prescription medication or over-the-counter (OTC) product (including natural food supplements, vitamins, herbs) within 14 days prior to dosing
• •18. Receipt of any vaccine or booster within 14 days prior to Day 1 or planned vaccination or booster within 4 weeks after IP administration
• •19. Any planned medical intervention or personal event that might interfere with the ability to comply with the study requirements
• •20. Is current study site staff paid entirely or partially by the contract for this trial, or staff who are supervised by the PI or sub-PI
• •21. Receipt of an investigational product, or participation in another trial involving a marketed or investigational drug within 30 days of Day 1, or 5 half-lives of the investigational drug, whichever is longer
• •22. Any other comorbidity or condition that, in the opinion of the Investigator would make the subject unsuitable for the study or unable to comply with the study requirements