First in Human Study in Subjects With Obesity, But Otherwise Healthy

Korábbi kezelés

• History of cholecystectomy <= 6 months prior to screening.
• 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.
• 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.
• Previous surgical treatment for obesity or any form of bariatric surgery.
• 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.
• Have received any vaccine ≤30 days prior to check-in.
• 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
• 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.

Más betegség

• Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2).
• History of pancreatitis.
• Current use of tobacco products or having a history of tobacco use within the past 6 months.
• 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).
• 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).
• Obesity that was induced by other endocrinologic disorders (e.g., Cushing's Syndrome).
• Evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies.
• Evidence of hepatitis C and/or positive hepatitis C antibody and hepatitis B, hepatitis B core antibody, and/or positive hepatitis B surface antigen.
• 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.
• Any lifetime history of a suicidal attempt or any suicidal behavior, as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS).
• History of malignancy of any type, other than basal cell carcinoma, occurring less than 5 years prior to randomization.
• 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.
• Estimated glomerular filtration rate of ≤60 mL/min for women and men (based on the Chronic Kidney Disease Epidemiology Collaboration equation) at the Screening.

Laborértékek

• History or clinical evidence of diabetes mellitus, including a fasting glucose of ≥ 120 mg/dL and/or HbA1c ≥ 6.5% at Screening.
• Triglycerides ≥500 mg/dL at Screening.
• 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 <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
• Albumin level <3.5 g/dL (<35 g/L) at Screening.
• Aspartate aminotransferase (AST) ≥1.25 × upper limit of normal (ULN) at Screening.
• Alanine aminotransferase (ALT) ≥1.25 × upper limit of normal (ULN) at Screening.
• Bilirubin >1.25 upper limit of normal (ULN) at Screening.
• Absolute neutrophil count <lower limit of normal (LLN) at Screening.
• Fasting low-density lipoprotein ≥160 mg/dL at Screening.
• Hemoglobin <LLN at Screening.
• Platelet count <LLN at Screening.

Egyéb

• Subjects with screening calcitonin level of ≥15 pg/mL (calcitonin levels will be monitored during the study).
• Regular consumption of caffeine-containing beverages, including coffee, tea, energy drinks, and caffeinated sodas, exceeding 3 cups per day.
• Untreated or uncontrolled hypo/hyperthyroidism defined as thyroid-stimulating hormone >6 mIU/L or <0.4 mIU/L.

• Willing and able to provide informed consent prior to initiation of any study specific procedures/activities.
• Males and females ≥18 to <=65 years of age, at the time of signing informed consent, who have been diagnosed with obesity, defined by BMI.
• Except for obesity, otherwise healthy or with stable, well controlled obesity-related conditions as determined by the investigator based on a medical evaluation including physical exam, medical history, laboratory tests, and ECGs.
• Body mass index (BMI) ≥ 30.0 kg/m2 to 45.0 kg/m2 (Obesity to be confirmed by Caliper test showing body fat percentage with the average or above the average level).
• Has maintained a stable body weight during the 3 months prior to Screening (<5% body weight change).
• 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.
• 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)
  • Note: bilateral salpingectomy is not an accepted sterilization method.
• 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)