A Phase I Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetic (PK) of Single-dose Administration of Semaglutide Nasal Spray (WL1006) in Adult Overweight or Obese Participants
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Temperature
研究概览
简要总结
The specific aim of this study is to examine the Safety, Tolerability and Pharmacokinetic of Semaglutide Nasal Spray compared with placebo and positive control in Adult Overweight or Obese Participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Male or female participants aged ≥18 years and ≤ 65 years.
- •Body Mass Index (BMI) at screening between 27.0 and 35.0 kg/m² (inclusive).
- •Weight change of no more than ±5% during the 3 months prior to screening with diet and exercise alone (self-reported).
- •Participants (including males) must have no plans for conception during the study and within 3 months after the last administration, and must agree to use effective contraceptive methods and refrain from donating sperm or eggs during this period.
- •Negative anti-HIV antibody test result at screening.
- •Participants must fully understand the trial objectives, nature, procedures, and potential adverse reactions, voluntarily participate, be able to communicate well with the investigators, comply with all study requirements, and sign the informed consent form before any study procedures begin.
排除标准
- •Diagnosis of type 1, type 2, or other forms of diabetes mellitus.
- •Prior diagnosis of obesity caused by monogenic mutations or other medical conditions, including but not limited to hypothalamic obesity, pituitary obesity, hypothyroidism-related obesity, Cushing's syndrome, insulinoma, acromegaly, or hypogonadism.
- •Prior history of bariatric surgery (excluding participants who had liposuction, abdominoplasty, intragastric balloon removal, or duodenal-jejunal bypass sleeve removal >1 year prior), or plan to undergo bariatric surgery or use weight-loss devices during the study.
- •Use of any of the following treatments within 3 months prior to screening:
- •Approved or unapproved anti-obesity medications (e.g., liraglutide, semaglutide, benaglutide, tirzepatide, orlistat, phentermine/topiramate, naltrexone/bupropion), or herbal supplements, health products, meal replacements, or weight-loss capsules that may affect body weight;
- •Any glucagon-like peptide-1 (GLP-1) receptor agonists, GLP-1 related multi-agonists (e.g., GLP-1/glucose-dependent insulinotropic polypeptide [GIP] dual agonists, GLP-1/glucagon [GCG] dual agonists, GLP-1/GIP/GCG triple agonists), or combination preparations containing GLP-1 receptor agonists;
- •Any antidiabetic medications (e.g., odium-glucose cotransporter-2 inhibitors (SGLT2) inhibitors, metformin, alpha-glucosidase inhibitors, insulin);
- •Any other treatments known to affect body weight (e.g., cause weight loss or weight gain), including:
- •Systemic corticosteroid therapy (intravenous or oral) for >1 week
- •Tricyclic antidepressants (e.g., imipramine, amitriptyline, doxepin)
- •Selective serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine, paroxetine, sertraline, fluvoxamine)
- •Antipsychotics/antiepileptics (e.g., imipramine, amitriptyline, mirtazapine, phenelzine, chlorpromazine HCl, clozapine, olanzapine, valproate derivatives, lithium preparations, thioridazine)
- •Antihistamines (e.g., cyproheptadine, ketotifen, astemizole).
- •Any investigational drugs, vaccines, or medical devices.
- •Laboratory abnormalities at screening meeting any of the following:
- •Glycated hemoglobin (HbA1c) ≥6.5% or fasting glucose ≥7.0 mmol/L;
- •Uncontrolled hypertension, systolic blood pressure (SBP) ≥160 mmHg and/or diastolic blood pressure (DBP) ≥100 mmHg;
- •Thyroid-stimulating hormone (TSH) >4.2 or <0.27 mIU/L;
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥1.5 × upper limit of normal (ULN), or total bilirubin ≥1.5 × ULN;
- •Fasting triglycerides >3.42 mmol/L;
- •Serum amylase or lipase ≥1.5×ULN;
- •Calcitonin > ULN;
- •Estimated glomerular filtration rate (eGFR) ≤80 mL/min/1.73 m²;
- •Clinically significant ECG findings: HR <40 or >100 bpm, second- or third- degree atrioventricular (AV) block, long QT syndrome, QTcF >450 ms (male) or >470 ms (female), left bundle branch block (LBBB), complete right bundle branch block (RBBB), Wolff-Parkinson-White (WPW) syndrome, or other clinically significant arrhythmias (e.g., paroxysmal supraventricular tachycardia (SVT), atrial flutter/fibrillation, ventricular flutter or fibrillation, sick sinus syndrome) deemed unsuitable by the investigator.
- •History of acute or chronic pancreatitis, or symptomatic gallbladder disease (except cholecystectomy).
- •Participants with clinically significant abnormalities during nasal examination (including external nose and nasal cavity inspection) as determined by the investigator at screening.
- •Nasal or sinus surgery or nasal trauma within 3 months prior to screening, not fully healed.
- •Presence of nasal mucosal erosion, septal ulceration/perforation, or other nasal conditions (e.g., acute or chronic sinusitis, drug-induced rhinitis, allergic rhinitis, nasal polyps) that may affect intranasal drug deposition, as determined by the investigator.
- •Participants with extensive scars or large tattoos on the abdomen, thighs, or upper arms that may interfere with drug administration.
- •History of thyroid disease or abnormal thyroid function requiring treatment, deemed clinically significant.
- •Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2).
- •Any malignancy diagnosed within 5 years (except cured basal cell carcinoma, cervical carcinoma in situ, localized prostate cancer post-surgery, or ductal carcinoma in situ post-surgery).
- •History of major cardiovascular or cerebrovascular events: a) MI, PCI/CABG, valvular surgery, clinically significant arrhythmias requiring treatment, unstable angina, TIA, stroke within 6 months prior to screening, b) NYHA Class III-IV heart failure.
- •Clinically significant gastrointestinal (GI) diseases at screening or within the screening period: pyloric obstruction, ileus, delayed gastric emptying, inflammatory bowel disease (IBD), gastroparesis, gastroesophageal reflux disease (GERD), active peptic ulcer.
- •Participants positive for hepatitis B surface antigen anti-hepatitis C virus antibody, or RPR at screening;
- •Participants with upper respiratory tract infection occurring within 7 days before administration.
- •Major depressive disorder or other severe psychiatric illness (e.g., schizophrenia, schizoaffective disorder, paranoid psychosis, bipolar disorder, epilepsy-related psychosis, intellectual disability with psychiatric symptoms) within 2 years before screening, or any history of self-harm or suicidal behavior, or participants with any suicidal ideation of type 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) or type 5 (Active Suicidal Ideation with Specific Plan and Intent) on the C-SSRS.
- •Blood donation within 3 months or total blood loss ≥400 mL within 6 months (excluding menstruation) prior to screening; planned donation within 3 months post-study.
- •History of vasovagal syncope or intolerance to venipuncture/IV cannulation.
- •Participants with a history of hypersensitivity or known/suspected allergy to GLP-1 receptor agonists or any excipients in the study drug formulation.
- •History of alcohol abuse within 1 year prior to screening through check-in, defined as an average consumption >14 units/week (1 unit = 360 mL beer, 45 mL 40% spirits, or 150 mL wine); unwilling to abstain from alcohol use during study, or a positive breath alcohol test (>0.0 mg/100 mL).
- •Smoking >5 cigarettes/day within 3 months prior to screening, or unwilling to abstain during study.
- •History of substance abuse (including non-medical use of narcotics or psychotropic substances) within 1 year prior to screening through check-in; Positive drug screening test for: morphine, methamphetamine ("ice"), 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"), tetrahydrocannabinol (THC, cannabis), etc.
- •Female Participants who are pregnant or breastfeeding, or with positive serum pregnancy test results at screening, or positive urine pregnancy test at check-in (Day -1);
- •Any other condition deemed by the investigator to render the participant unsuitable for participation.
研究组 & 干预措施
Cohort A0 : Semaglutide Nasal Spray
干预措施: Semaglutide Nasal Spray (Drug)
Cohort A1: Semaglutide nasal spray and placebo
干预措施: Semaglutide Nasal Spray (Drug)
Cohort A1: Semaglutide nasal spray and placebo
干预措施: Placebo (Drug)
Cohort A2:Semaglutide nasal spray and placebo
干预措施: Semaglutide Nasal Spray (Drug)
Cohort A2:Semaglutide nasal spray and placebo
干预措施: Placebo (Drug)
Cohort A3: Semaglutide injection
干预措施: Semaglutide Injection (Drug)
结局指标
主要结局
Temperature
时间窗: Day 1 to Day 36 after administration
Pulse
时间窗: Day 1 to Day 36 after administration
Red blood cell count
时间窗: Day 1 to day 36
Respiratory rate
时间窗: Day 1 to Day 36 after administration
White blood cell count
时间窗: Day 1 to day36
Platelet count
时间窗: Day 1 to day 36
Neutrophil percentage
时间窗: day 1 to day 36
Blood pressure
时间窗: Day 1 to Day 36 after administration
Urinalysis
时间窗: Day 1 to Day 36 after administration
Eosinophil percentage
时间窗: day 1 to day 36
Area under the concentration-time curve from time 0 to time t (AUC0-t)
时间窗: Day 1 to Day 36 after administration
Hematocrit
时间窗: Day 1 to Day 36 after administration
Percentage of AUC extrapolated(AUC%Extrap)
时间窗: Day 1 to Day 36 after administration
Area under the concentration-time curve from time 0 to infinity(AUC0-∞)
时间窗: Day 1 to Day 36 after administration
Maximum Plasma Concentration (Cmax)
时间窗: Day 1 to Day 36 after administration
Time to maximum concentration(Tmax)
时间窗: Day 1 to Day 36 after administration
Elimination half-life / Terminal half-life(t1/2)
时间窗: Day 1 to Day 36 after administration
Apparent volume of distribution during terminal phase, adjusted for bioavailability (Vz/F)
时间窗: Day 1 to Day 36 after administration
Apparent clearance, adjusted for bioavailability(CL/F)
时间窗: Day 1 to Day 36 after administration
Terminal elimination rate constant(λz)
时间窗: Day 1 to Day 36 after administration
Absolute bioavailability(F)
时间窗: Day 1 to Day 36 after administration
Incidence and severity of treatment emergent adverse events (TEAEs)
时间窗: Day 1 to Day 36 after administration
12-Lead-ECGs(Electrocardiograms )
时间窗: Day 1 to Day 36 after administration
Blood biochemistry
时间窗: Day 1 to Day 36 after administration
Alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, γ-glutamyl transferase, alkaline phosphatase, total protein, albumin, urea, uric acid, creatinine, calcium, chloride, potassium, sodium, phosphorus, total cholesterol, triglycerides, fasting blood glucose, creatine kinase, lactate dehydrogenase, amylase, lipase.
Thyroid function
时间窗: Day 1 to Day 36 after administration
Thyroid-stimulating hormone, total tri-iodothyronine, total thyroxine, free tri-iodothyronine, free thyroxine
Virology test
时间窗: Day 1 to Day 36 after administration
Urine pregnancy test
时间窗: Day 1 to Day 36 after administration
Physical examination, includes: head, ears, eyes, nose and throat, skin, lymph nodes, neck, chest, abdomen, heart, cardiovascular, musculoskeletal system/extremities, neurological system and body weight.
时间窗: Day 1 to Day 4 after administration
Hemoglobin
时间窗: Day 1 to Day 36 after administration
Basophil percentage
时间窗: day 1 to day 36
Monocyte percentage
时间窗: day 1 to day 36
Lymphocyte percentage
时间窗: day 1 to day 36
Activated partial thromboplastin time
时间窗: Day 1 to day 36
Prothrombin time
时间窗: day 1 to day 36
Fibrinogen
时间窗: day 1 to day 36
Thrombin time
时间窗: day 1 to day 36
次要结局
- Positive rate of Anti-Drug Antibody (ADA)(Day 1 to Day 29 after administration)
- Titer of Anti-Drug Antibody (ADA)(Day 1 to Day 29 after administration)
- Positive rate of Neutralizing antibody (Nab)(Day 1 to Day 29 after administration)
- Titer of Neutralizing antibody (Nab)(Day 1 to Day 29 after administration)