A Single Center, Single Dose, Double-blind, Randomized, Placebo-Controlled, Dose-Escalating Study to Evaluate Safety, Tolerability and Pharmacokinetics of Subcutaneously Administered MD-18 in Healthy Subjects.
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- To determine the safety of a single subcutaneously administered dose of MD-18 in healthy subjects, as assessed by the collection of Adverse Events.
研究概览
简要总结
A Single Center, Single Dose, Double-blind, Randomized, Placebo-controlled Dose-Escalating Study to Evaluate Safety, Tolerability and Pharmacokinetics of Subcutaneously Administered MD-18 in healthy subjects.
详细描述
This study will be conducted as a single-center study. A single escalating dose of MD-18 will be administered to each subject with a seven-day follow-up. 35 subjects will be enrolled. Cohorts will receive doses of 40. 80, 160, 240 or 320 milligram of MD-18 using 5:2 (active: placebo) randomization. Sentinel dosing will be used, consisting of enrolling three subjects at a 2:1 active to placebo ratio followed by the remaining subjects in the respective dose cohorts enrolled 48 hours later. Each of the 5 dose cohorts will enroll five active and two placebo subjects, with a total of 25 subjects receiving active therapy across the 5 arms and 10 subjects receiving placebo. The study will be conducted on an in-patient basis for the first 24 hours, followed by discharge and telephone check-in at 48 and 72 hours and return for follow-up visit at 7 days after administration of a single dose of MD-18.
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
- Double (Participant, Investigator)
盲法说明
Study medication will be supplied in labelled vials, clearly identifying the contents and indicating that the product is an investigational drug. An unblinded pharmacist at the clinical site will be responsible for drawing up the appropriate amount of study medication into a syringe and labelling the syringe for administration to the specific patient according to the randomization scheme.
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects aged 18-70 years, both genders.
- •Healthy as determined by a physician, based on history, medical examination, vital signs, laboratory tests, cardiac monitoring and respiratory function. History must comply with the following:
- •Absence of clinically significant illness or surgery within the preceding 12 weeks.
- •Absence of clinically significant history of neurological, endocrine, cardiovascular, pulmonary, hematological, immunologic, psychiatric, gastrointestinal, renal, hepatic, and/or metabolic disease.
- •Male subjects with female partners of childbearing potential must agree to utilize an approved contraceptive during the study.
- •Female subjects of child-bearing potential with negative urine pregnancy tests and who agree to use contraception during the study.
- •Female subjects of non-child-bearing potential (i.e. tubal ligation, hysterectomy, or postmenopausal).
- •Body mass index (BMI) of 18.5-39.9 kg/m2
排除标准
- •History of excessive alcohol use (defined as >21 drinks per week for males and >14 drinks per week for females), recreational drug use or drugs of abuse within the past three months, or failure on urinary drug screen. Note: use of Cannabinoids for medical purposes is allowed.
- •Pregnant or breastfeeding within six months of screening assessment.
- •Substantial changes in eating habits or exercise routine within the preceding three months.
- •Evidence of eating disorders.
- •>5% weight change in the past three months.
- •Bariatric surgery within the past five years.
- •Significant renal impairment glomerular filtration rate (GFR) <60 milligram/milliliter/1.73m2).
- •Liver function tests (i.e., alanine aminotransferase, Aspartate Amino Transferase, alkaline phosphatase) greater than twice the upper limit of normal upon repeated measurements.
- •Diseases interfering with metabolism and/or ingestive behavior (e.g., myxedema, Cushing's disease, schizophrenia, major psychoses, unmanaged depression).
- •Use of drugs approved for the treatment of obesity.
- •Any clinically significant abnormality following the Investigator's review of the physical examination and clinical laboratory tests.
- •A baseline prolongation of ventricular activation and recovery interval after repeated measurements of >450 millisecond; a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease, or a family history of Long QT Syndrome (LQTS).
- •Participation in an investigational drug trial within three months prior to dosing in the present study.
研究组 & 干预措施
40 milligram (mg) MD-18 OR 40 milligram(mg) Placebo
A single dose of subcutaneous injection of 40mg MD-18 OR 40mg Placebo will be given on day zero.
干预措施: MD-18 (Drug)
80 milligram (mg) MD-18 OR 80 milligram (mg) Placebo
A single dose of subcutaneous injection of 80mg MD-18 OR 80mg Placebo will be given on day zero.
干预措施: MD-18 (Drug)
160 milligram (mg) MD-18 OR 160 milligram (mg) Placebo
A single dose of subcutaneous injection of 160mg MD-18 OR 160mg Placebo will be given on day zero.
干预措施: MD-18 (Drug)
240 milligram (mg) MD-18 OR 240 milligram (mg) Placebo
A single dose of subcutaneous injection of 240mg MD-18 OR 240mg Placebo will be given on day zero.
干预措施: MD-18 (Drug)
320 milligram (mg)MD-18 OR 320 milligram (mg) Placebo
A single dose of subcutaneous injection of 320mg MD-18 OR 320mg Placebo will be given on day zero.
干预措施: MD-18 (Drug)
结局指标
主要结局
To determine the safety of a single subcutaneously administered dose of MD-18 in healthy subjects, as assessed by the collection of Adverse Events.
时间窗: For all study duration (approximately two months).
Adverse Events Collection.
To determine the safety of a single subcutaneously administered dose of MD-18 in healthy subjects, as assessed by the collection of pre and post dose pharmacokinetics samples.
时间窗: Before and after dose administration on Days 0 and 1.
Pharmacokinetics sampling is predicated on a T1/2 less than 6 hours to enable inpatient monitoring for 4-5 half-lives.
To determine the safety of a single subcutaneously administered dose of MD-18 in healthy subjects, as assessed by the collection of vital signs.
时间窗: On screening visit and on days 1 and 7.
Systolic and diastolic blood pressure in millimeters of mercury, Heart rate in beats per minute, Respiratory rate in breath per minute.
To determine the safety of a single subcutaneously administered dose of MD-18 in healthy subjects, as assessed by the collection of Lab samples.
时间窗: On screening visit and on days 1 and 7.
Collection of Complete blood count, Serum chemistry, Coagulation panel and Urine analysis.
To determine the safety of a single subcutaneously administered dose of MD-18 in healthy subjects, as assessed by the collection of anthropometric measurement's.
时间窗: On screening visit and on days 1 and 7. (height will be collected only in the screening visit).
Weight in kilograms, Height in meters.
To determine the safety of a single subcutaneously administered dose of MD-18 in healthy subjects, as assessed by an electrocardiogram examination.
时间窗: On screening visit and on days 0,1 and 7.
12-lead ECG will be obtained within 1 hour before and 3 hours (+15 minutes) after dosing and prior to discharge. The ECG machine will automatically calculate the heart rate, measure of the time from the beginning of the atrial depolarization to the beginning of the ventricular depolarization, depolarization of ventricles and time taken for ventricular depolarization and repolarization. At each time-point, ECG will be obtained in triplicate.
To determine the safety of a single subcutaneously administered dose of MD-18 in healthy subjects, as assessed by physical examination.
时间窗: On screening visit and on days 1 and 7.
A complete physical examination (head, eyes, ears, nose and throat, heart, lungs, abdomen, skin, cervical and axillary lymph nodes, neurological, and musculoskeletal systems) will be performed.
次要结局
- Analysis of pharmacokinetics samples of MD-18 by lab methods.(Before and after dose administration on Days 0 and 1.)