A Phase 1, Randomized, Placebo-Controlled, Double-Blind First in Human, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of DA-1726 in Participants With Obesity.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 139
- 试验地点
- 1
- 主要终点
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Masking is to be done at the pharmacy level. The pharmacists that do not have other responsibilities in the study will prepare and administer the drug.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •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)
排除标准
- •History or clinical evidence of diabetes mellitus, including a fasting glucose of ≥ 120 mg/dL and/or HbA1c ≥ 6.5% at Screening.
- •Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2).
- •History of cholecystectomy <= 6 months prior to screening.
- •Subjects with screening calcitonin level of ≥15 pg/mL (calcitonin levels will be monitored during the study).
- •Triglycerides ≥500 mg/dL at Screening.
- •History of pancreatitis.
- •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
- •Regular consumption of caffeine-containing beverages, including coffee, tea, energy drinks, and caffeinated sodas, exceeding 3 cups per day.
- •Current use of tobacco products or having a history of tobacco use within the past 6 months.
- •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 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).
- •Untreated or uncontrolled hypo/hyperthyroidism defined as thyroid-stimulating hormone >6 mIU/L or <0.4 mIU/L.
- •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.
- •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.
- •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.
- •Have received any vaccine ≤30 days prior to check-in.
- •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.
- •Estimated glomerular filtration rate of ≤60 mL/min for women and men (based on the Chronic Kidney Disease Epidemiology Collaboration equation) at the Screening.
- •Fasting low-density lipoprotein ≥160 mg/dL at Screening.
- •Hemoglobin <LLN at Screening.
- •Platelet count <LLN at Screening.
- •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
- 另有 8 项未显示
研究组 & 干预措施
Part 3 - Titration
Multiple 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, using either 1-step or 2-steps titration.
干预措施: Placebo to DA-1726 (Drug)
Part 3 - Titration
Multiple 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, using either 1-step or 2-steps titration.
干预措施: DA-1726 (Drug)
Part 1 - Single Ascending Dose
Single 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.
干预措施: Placebo to DA-1726 (Drug)
Part 2 - Multiple Ascending Dose
Multiple 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.
干预措施: DA-1726 (Drug)
Part 2 - Multiple Ascending Dose
Multiple 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.
干预措施: Placebo to DA-1726 (Drug)
Part 1 - Single Ascending Dose
Single 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.
干预措施: DA-1726 (Drug)
结局指标
主要结局
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
时间窗: From date of randomization (baseline) until the discontinuation (up to 24 weeks post-dose baseline)
AEs, SAEs, TEAEs and AEs leading to treatment discontinuation.
次要结局
- Pharmacokinetic(From date of randomization (baseline) until the study discontinuation (up to 24 weeks post-dose baseline))
- Immunogenicity(From date of randomization (baseline) until the end of the study (up to 24 weeks post-dose baseline))
- Pharmacodynamics(From date of randomization (baseline) until the discontinuation (up to 24 weeks post-dose baseline))