first in human study in subjects with obesity, but otherwise healthy

Conditions: Obesity

Summary: this is a first in human study to evaluate the safety and tolerability of da-1726 following single and multiple doses in participants with obesity, but otherwise healthy subjects.

this is a phase 1, randomized, placebo-controlled, double-blind, sequential parallel group study to investigate the safety, tolerability, pharmacokinetics (pk), and pharmacodynamics (pd) of single and multiple ascending doses of da-1726 in adult participants (aged 18 to 65 years) with obesity (bmi ≥30 - 45 kg/m2). da-1726 will be administered via subcutaneous (sc) injection within the clinic setting.

Eligibility criteria:
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 \ 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 : * 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 \ 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.