NCT03673111已完成1 期
A Randomised, Placebo Controlled First in Human Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Y14 in Adult Subjects
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 77
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (Safety and Tolerability)
研究概览
简要总结
A randomised, placebo controlled Phase I study to investigate investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of Y14 in adult subjects.
详细描述
Objectives:
Primary Objective
- To investigate the safety and tolerability of single doses of Y14 in overweight/obese but otherwise healthy male subjects.
- To investigate the safety and tolerability of multiple doses of Y14 in overweight/obese male subjects with normal glucose tolerance, Type 2 diabetes or prediabetes.
Secondary Objectives
- To assess the pharmacokinetic (PK) profile of single doses of Y14 in overweight/obese but otherwise healthy male subjects.
- To assess the PK profile of multiple ascending doses of Y14 in overweight/obese male subjects with normal glucose tolerance, Type 2 diabetes or prediabetes.
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, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Adult males aged 18 to 65 years inclusive with BMI between 25.0 and 38.0 kg/m2 inclusive;
- •(PART B only) Subjects who have normal glucose tolerance, Type 2 diabetes, impaired glucose tolerance or impaired fasting glucose according to WHO 2006 and 2011 criteria;
- •Subjects who are otherwise healthy enough to participate, as determined by pre-study medical history, physical examination and 12-lead ECG;
- •Subjects whose clinical laboratory test results are either within the normal range or if outside this range the abnormalities are judged to be not clinically relevant and are acceptable to the Investigator;
- •Subjects who are negative for hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) I and II tests at screening;
- •Subjects who are negative for drugs of abuse and alcohol tests at screening and admissions;
- •Subjects who are non-smokers for at least 3 months preceding screening;
- •Subjects who agree to use medically acceptable methods of contraception for at least 3 months after study drug administration;
- •Subjects who agree not to donate sperm for at least 3 months after study drug administration;
- •Subjects who are able and willing to give written informed consent.
排除标准
- •Subjects who do not conform to the above inclusion criteria;
- •Subjects who have a clinically relevant history or presence of gastrointestinal (especially associated with vomiting), respiratory, renal, hepatic, haematological, lymphatic, neurological (especially if associated with balance disorders or vomiting e.g. migraine or labyrinthitis), cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders;
- •Subjects who have a clinically relevant surgical history;
- •Subjects who are currently taking any of the following classes of diabetes medications: thiazolidinediones, dipeptidyl peptidase IV inhibitors ('gliptins'), GLP-1 analogues, and insulin;
- •Subjects who have a history of relevant and severe atopy e.g. asthma, angioedema requiring emergency treatment, severe hayfever requiring regular treatment (i.e. taking antihistamines and/or glucocorticoids more regularly than 3 times a week), severe eczema requiring regular treatment (i.e. taking antihistamines and/or glucocorticoids more regularly than 3 times a week);
- •Subjects who have a history of relevant drug hypersensitivity;
- •Subjects who have a history of alcohol abuse or alcohol dependence according to DSMIV criteria within the last 2 years;
- •Subjects who have a history of drug or substance abuse according to DSM-IV criteria within the last 2 years;
- •Subjects who have a history of clinically significant migraine as judged by the Investigator. Subjects can be included if they have not had a migraine for the last 3 years;
- •Subjects with a history of pancreatitis or pancreatic cancer;
- •Subjects who consume more than 21 units of alcohol a week (unit = 1 glass of wine (125 mL) = 1 measure of spirits = ½ pint of beer);
- •Subjects who have a significant infection or known inflammatory process on screening;
- •Subjects who have acute gastrointestinal symptoms at the time of screening or admission (e.g. nausea, vomiting, diarrhoea, heartburn);
- •Subjects who have an acute infection such as influenza at the time of screening or admission;
- •Subjects who have used prescription drugs within 2 weeks of first dosing. For Part B, patients are allowed to be treated for their diabetes with monotherapy with a sulphonylurea, metformin, or a SGLT-2 inhibitor, dual therapy with any two of the following drug types: a sulphonylurea, metformin, and/or a SGLT-2 inhibitor; triple therapy with a sulphonylurea, metformin, and a SGLT-2 inhibitor. In addition patients in Part B are allowed to take hypolipidaemic and/or antihypertensive treatments, provided that the doses have not been altered within the 4 weeks prior to entering the study. Other medications may be allowed if the Investigator and Sponsor both agree that they will not affect the outcome of the study or the safety of the subject.
- •Subjects who have used over the counter medication excluding routine vitamins and paracetamol but including megadose (intake of 20 to 600 times the recommended daily dose) vitamin therapy within 7 days of first dosing, unless agreed as not clinically relevant by the Principal Investigator and Sponsor;
- •Subjects who have donated blood within 3 months prior to screening; Subjects who have donated plasma within the 7 days prior to screening; Subjects who have donated platelets within the 6 weeks prior to screening
- •Subjects who have used any investigational drug in any clinical trial within 3 months of their first admission date;
- •Subjects who have received the last dose of investigational drug greater than 3 months ago but who are on extended follow-up;
- •Subjects who have previously received Y14;
- •Subjects who are vegans, vegetarian or have any dietary restriction (unless agreed as not clinically relevant by the PI and Sponsors);
- •Subjects who cannot communicate reliably with the Investigator;
- •Subjects who are unlikely to co-operate with the requirements of the study;
- •History or evidence of abnormal eating behaviour, as observed through the Dutch Eating Behaviour (DEBQ) and SCOFF questionnaires at screening.
研究组 & 干预措施
18.0 mg Y14 (A5) with varied formulation
Experimental
Y14 single dose, subcutaneous
干预措施: Y14 (Drug)
1.0 mg Y14 (A1)
Experimental
Y14 single dose, subcutaneous
干预措施: Y14 (Drug)
2.0 mg Y14 (A1)
Experimental
Y14 single dose, subcutaneous
干预措施: Y14 (Drug)
6.0 mg Y14 (A1)
Experimental
Y14 single dose, subcutaneous
干预措施: Y14 (Drug)
9.0 mg Y14 (A2) with varied formulation
Experimental
Y14 single dose, subcutaneous
干预措施: Y14 (Drug)
36.0 mg Y14 (A6) with varied formulation
Experimental
Y14 single dose, subcutaneous
干预措施: Y14 (Drug)
Placebo (B)
Placebo Comparator
5 subcutaneous injections of 0.9% saline, over a 4 week treatment period
干预措施: Placebo (Drug)
9-26.0 mg (B1)
Experimental
Y14 multiple dose, subcutaneous 5 doses over a 4 week treatment period: escalating doses to a max of 26 mg
干预措施: Y14 (Drug)
9-36 mg (B2)
Experimental
Y14 multiple dose, subcutaneous 4 doses over a 4 week treatment period: escalating doses to a max of 36 mg
干预措施: Y14 (Drug)
12-36 mg (B3)
Experimental
Y14 multiple dose, subcutaneous 4 doses over a 4 week treatment period: escalating doses to a max of 36 mg
干预措施: Y14 (Drug)
Placebo (A)
Placebo Comparator
Single subcutaneous injection of 0.9% saline
干预措施: Placebo (Drug)
9 mg Y14 (A3) with varied formulation
Experimental
Y14 single dose, subcutaneous
干预措施: Y14 (Drug)
9 mg Y14 (A4) with varied formulation
Experimental
Y14 single dose, subcutaneous
干预措施: Y14 (Drug)
18 mg Y14 (A7) with varied formulation
Experimental
Y14 single dose, subcutaneous
干预措施: Y14 (Drug)
36 mg Y14 (A8) with varied formulation
Experimental
Y14 single dose, subcutaneous
干预措施: Y14 (Drug)
36 mg Y14 (A9) with varied formulation
Experimental
Y14 single dose, subcutaneous
干预措施: Y14 (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (Safety and Tolerability)
时间窗: Up to 73 days after dosing
As assessed by reporting of adverse events, vital signs, physical examination, clinical laboratory safety assessments, and ECG parameters. Possibly or definitely related to study drug
次要结局
- Cmax(For Part A, Cohorts A3 to A9 - up to 840 hour post dose. For Part B - up to day 70 post 1st dose)
- AUC 0-72h(Up to 72hr after dosing)
- AUC 0-τ(Up to 168h after dosing)
- T 1/2(For Part A, Cohorts A3 to A9 - up to 840 hour post dose. For Part B - up to day 70 post 1st dose)
研究者
研究点 (1)
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