Description
Inclusion Criteria:
- 1. Willing and able to provide informed consent prior to initiation of any study specific procedures/activities.
- 2. Males and females ≥18 to \<=65 years of age, at the time of signing informed consent, who have been diagnosed with obesity, or have signs/symptoms consistent with obesity.
- 3. Except for obesity, otherwise healthy as determined by the investigator based on a medical evaluation including physical exam, medical history, laboratory tests, and ECGs.
- 4. Body mass index (BMI) ≥ 30 kg/m2 to 45 kg/m2 (Obesity to be confirmed by Caliper test).
- 5. Has maintained a stable body weight during the 3 months prior to Screening (\<5% body weight change).
- 6. Willing to maintain current diet and physical activity regimen.
- * SAD Cohorts (Be willing to eat a standard diet while in the Clinical Research Unit).
- * MAD Cohorts (Be willing to eat a standard diet while in the Clinical Research Unit). If appetite decreases, participants may not maintain their current diet.
- 7. Females must be of non-reproductive potential:
- * Postmenopausal defined as:
- * Age of ≥55 years with no menses for at least 12 months; OR
- * Age \<55 years with no menses for at least 12 months AND with a follicle-stimulating hormone level \>40 IU/L or according to the definition of "postmenopausal range" for the laboratory involved; OR
- * History of hysterectomy; OR
- * History of bilateral oophorectomy
- * History of tubal ligation (surgically sterile)
- 8. Males must agree to practice an acceptable method of effective birth control while on study through 5 half-lives plus one week after receiving last dose of DA-1726.
- Acceptable methods of birth control include:
- * Sexual abstinence
- * Vasectomy and testing that shows there are no sperm in semen.
- * Condom with spermicide (male) in combination with barrier methods (diaphragm, cervical cap, or cervical sponge), hormonal birth control, or IUS (females)
Exclusion Criteria:
- 1. History or clinical evidence of diabetes mellitus, including a fasting glucose of ≥ 120 mg/dL and/or HbA1c ≥ 6.5% at Screening.
- 2. Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2).
- 3. History of cholecystectomy \< 6 months prior to screening.
- 4. Subjects with screening calcitonin level of ≥15 pg/mL (calcitonin levels will be monitored during the study).
- 5. Triglycerides ≥500 mg/dL at Screening.
- 6. History of pancreatitis.
- 7. Have a medical history or current evidence of clinically significant cardiac condition as evidenced by any of the following at Screening or check-in:
- * QTc at Screening from locally generated data of \>450 msec in males or \>470 msec in females or history of long QT syndrome
- * Supine systolic BP higher than 150 mmHg and a supine diastolic BP higher than 95 mmHg at Screening or check-in
- * Supine HR of \<50 or \>100 beats per minute on 2 of 3 triplicate ECGs at Screening or check-in
- * Heart block of the 1st, 2nd, or 3rd degree
- * Sick sinus syndrome (irregular heartbeat patterns)
- * Disorders in cardiac conduction
- * Peripheral blood circulation issues
- * Heart valve conditions
- * Cardiomyopathy
- * History of myocardial infarction
- * Unstable angina
- * History of heart artery bypass surgery
- * History of stroke
- * History of heart failure
- 8. Regular consumption of caffeine-containing beverages, including coffee, tea, energy drinks, and caffeinated sodas, exceeding 3 cups per day.
- 9. Current use of tobacco products or having a history of tobacco use within the past 6 months.
- 10. Have significant previous or current history of comorbidities capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the investigational product; or of interfering with the interpretation of data.
- 11. History of GI abnormality that could affect GI motility (including small bowel or colonic resection, inflammatory bowel disease, irritable bowel syndrome, gastroparesis \[clinically significant gastric emptying abnormality\], and colon / GI tract cancer).
- 12. Have a history of chronic medical conditions involving the heart, liver, or kidneys (e.g., atherosclerotic coronary vascular disease (ASCVD), heart failure, liver cirrhosis, chronic kidney disease).
- 13. Untreated or uncontrolled hypo/hyperthyroidism defined as thyroid-stimulating hormone \>6 mIU/L or \<0.4 mIU/L.
- 14. Obesity that was induced by other endocrinologic disorders (e.g., Cushing's Syndrome).
- 15. Evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies.
- 16. Evidence of hepatitis C and/or positive hepatitis C antibody and hepatitis B, hepatitis B core antibody, and/or positive hepatitis B surface antigen.
- 17. Have a history or presence of psychiatric disorders that would present a safety risk or may significantly impair the participant's ability to comply with study procedures.
- 18. Any lifetime history of a suicidal attempt or any suicidal behavior, as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS).
- 19. History of malignancy of any type, other than basal cell carcinoma, occurring less than 5 years prior to randomization.
- 20. History of substance abuse (i.e., alcohol or illicit substances) within 12 months prior to Screening; and/or a positive test for alcohol/drugs of abuse at Screening.
- 21. Previous surgical treatment for obesity or any form of bariatric surgery.
- 22. Currently receiving treatment in another investigational drug or device study or 5 half lives or 30 days since last dose of investigational drug, whichever is longer.
- 23. Participants with a history of significant allergic or drug reactions (NSAIDs or antibiotics) or known allergy to DA 1726 excipients that would place them at increased risk.
- 24. Have received any vaccine ≤30 days prior to check-in.
- 25. Albumin level \<3.5 g/dL (\<35 g/L) at Screening.
- 26. Aspartate aminotransferase (AST) ≥1.25 × upper limit of normal (ULN) at Screening.
- 27. Alanine aminotransferase (ALT) ≥1.25 × upper limit of normal (ULN) at Screening.
- 28. Bilirubin \>1.25 upper limit of normal (ULN) at Screening.
- 29. Absolute neutrophil count \<lower limit of normal (LLN) at Screening.
- 30. Estimated glomerular filtration rate of ≤60 mL/min for women and men (based on the Chronic Kidney Disease Epidemiology Collaboration equation) at the Screening.
- 31. Fasting low-density lipoprotein ≥160 mg/dL at Screening.
- 32. Hemoglobin \<LLN at Screening.
- 33. Platelet count \<LLN at Screening.
- 34. Current or history of treatment with medications that may cause significant weight gain, within 3 months of Screening, including:
- * Systemic corticosteroids (except for a short course of treatment, i.e., 7-10 days)
- * Tricyclic antidepressants
- * Atypical antipsychotics
- * Mood stabilizers (e.g., imipramine, amitriptyline, mirtazapine, paroxetine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid and its derivatives, and lithium)
- * Antidiabetic Medications (e.g., insulin or certain sulfonylureas, that may lead to weight gain)
- * Beta-blockers (e.g., the ones used to treat conditions like hypertension that may cause weight gain)
- * Antihistamines (particularly the first-generation ones, that may have sedative effects and could potentially contribute to weight gain)
- * Contraceptives
- * Any non-steroidal anti-inflammatory drugs
- 35. Current participation (or within the last 3 months) in an organized weight reduction program or currently using or has used within 3 months prior to Screening: pramlintide, sibutramine, orlistat, zonisamide, topiramate, phentermine, naltrexone, lorcaserin, liraglutide, semaglutide, tirzepatide or metformin.
Ages Eligible for Study:
18 Years to 65 Years (ADULT, OLDER_ADULT)
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
No