A Phase 1, Double-blind, Single and Multiple-Dose Study of Safety, Tolerability and Pharmacokinetics of Amilo-5MER in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- Safety and tolerability of amilo-5ER
研究概览
简要总结
This is a three-part, single Centre, double-blind, randomized, placebo-controlled first-in-human study of single ascending doses (SADs, Part 1) and multiple doses (Part 2) of amilo-5MER in healthy young adult male subjects and a single dose cohort in healthy elderly male and female subjects (Part 3)
详细描述
This is a three-part, single Centre, double-blind, randomized, placebo-controlled first-in-human study of single ascending doses (SADs, Part 1) and multiple doses (Part 2) of amilo-5MER in healthy young adult male subjects and a single dose cohort in healthy elderly male and female subjects (Part 3).
The study aim is to assess and characterize the safety and tolerability of single and multiple doses of amilo-5MER in healthy young adult subjects and single doses in healthy elderly subjects.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Subjects were assigned to a treatment using a computer-generated randomization schedule.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy males (all parts) or healthy females (Part 3 only).
- •Aged 18 to 45 years (Parts 1 and 2) or aged 65 to 80 years (Part 3) inclusive at the time of signing informed consent.
- •Body mass index (BMI) of 19.0 to 31.0 kg/m2, with a body weight <95 kg, as measured at screening.
- •Willing and able to communicate and participate in the whole study.
- •Provided a written informed consent.
- •Agreed to adhere to the contraception requirements
排除标准
- •Subjects who had received any IMP in a clinical research study within the 90 days prior to Day
- •Subjects who were, or were immediate family members of, a study site or sponsor employee.
- •Subjects who had previously been administered IMP in this study. Subjects who took part in Part 1 were not permitted to take part in Part
- •Evidence of recent SARS-CoV-2 symptomatic infection within the last 3 months. Subjects who had asymptomatic, incidental, positive polymerase chain reaction (PCR) findings could have been included if tested more than 30 days prior to screening and test negative at screening.
- •History of any drug or alcohol abuse in the past 2 years.
- •Regular alcohol consumption in males >21 units per week and females (Part 3 only) >14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type).
- •A confirmed positive alcohol breath test at screening or admission.
- •Current smokers and those who had smoked within the last 6 months. A confirmed breath carbon monoxide (CO) reading of greater than 10 ppm at screening or admission.
- •Current users of e-cigarettes and nicotine replacement products and those who had used these products within the last 6 months.
- •Females of childbearing potential including those who were pregnant or lactating (all female subjects must have had a negative highly sensitive urine and serum pregnancy test). A woman was considered of childbearing potential unless she was permanently sterile (hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) or was postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle stimulating hormone [FSH] concentration ≥30 IU/L) at screening and admission visit (Part 3 only).
- •Male subjects who had pregnant or lactating partners.
- •Subjects who did not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening.
- •Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the investigator (laboratory parameters are listed in Appendix 1 of protocol [Appendix 16.1.1.1]).
- •Confirmed positive drugs of abuse test result (drugs of abuse tests are listed in Appendix 1 of protocol [Appendix 16.1.1.1]) at screening or admission.
- •Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody results.
- •Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of <80 mL/min (Parts 1 and 2) or <60 mL/min (Part 3) using the Cockcroft-Gault equation at screening.
- •History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator.
- •Clinically significant abnormalities on electrocardiogram (ECG) (e.g. prolonged QTc, prolonged PR interval).
- •Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients.
- •Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever was allowed unless it was active.
- •Donation of blood or plasma within the previous 3 months or loss of greater than 400 mL of blood.
- •Had received blood or plasma derivatives in the 3 months preceding dosing.
- •Adherence (for whatever reason) to an abnormal diet during the 4 weeks prior to the study, or subjects with recent significant change in body weight.
- •Subjects who were taking, or had taken, any prescribed or over-the-counter drug (other than up to 2 g of paracetamol per day until 24 h prior to dosing and hormone replacement therapy [HRT]) or herbal remedies or dietary supplements (including bran) in the 14 days before IMP administration.
- •Subjects with tattoos or scars on the abdomen which could have interfered with injection site assessments, as determined by the investigator at screening.
- •Failure to satisfy the investigator of fitness to participate for any other reason.
研究组 & 干预措施
A- amilo-5MER solution for subcutaneous administration or matching placebo- 10 mg
Amilo-5MER solution for subcutaneous administration or matching placebo at a dose of 10 mg
干预措施: amilo-5MER (Drug)
B- amilo-5MER solution for subcutaneous administration or matching placebo- 30 mg
Amilo-5MER solution for subcutaneous administration or matching placebo at a dose of 30 mg
干预措施: amilo-5MER (Drug)
C- amilo-5MER solution for subcutaneous administration or matching placebo- 90 mg
Amilo-5MER solution for subcutaneous administration or matching placebo at a dose of 90 mg
干预措施: amilo-5MER (Drug)
D- amilo-5MER solution for subcutaneous administration or matching placebo- 180 mg
Amilo-5MER solution for subcutaneous administration or matching placebo at a dose of 180 mg
干预措施: amilo-5MER (Drug)
E- amilo-5MER solution for subcutaneous administration or matching placebo- 360mg
Amilo-5MER solution for subcutaneous administration or matching placebo at a dose of 360 mg
干预措施: amilo-5MER (Drug)
结局指标
主要结局
Safety and tolerability of amilo-5ER
时间窗: 10 days
Assess and characterize the number of participants with clinically significant changes in safety assessments, including adverse events, physical examination findings, vital signs, clinical laboratory assessments, and urinalysis.
次要结局
- PK- Area under the concentration-time curve (AUC)(10 days)
- PK- Maximum observed concentration (Cmax)(10 days)
- PK- Time of maximum observed concentration (Tmax)(10 days)
- PK- Total body clearance (CL/F)(10 days)