A Randomised, Placebo Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Gut Hormone Analogue G3215 in Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 90
- 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 the safety, tolerability, pharmacokinetics and pharmacodynamics of G3215 in adult subjects.
详细描述
Objectives:
Primary Objective
- To investigate the safety and tolerability of single doses of G3215 in overweight but otherwise healthy male subjects.
- To investigate the safety and tolerability of multiple doses of G3215 in overweight male subjects with mild stable Type 2 diabetes or prediabetes.
Secondary Objectives • To assess the pharmacokinetic (PK) profile of single and multiple ascending doses of G3215 in overweight but otherwise healthy male subjects or overweight / obese male subjects with mild stable Type 2 diabetes or prediabetes.
Exploratory Objective
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Adult males aged 18 to 60 years inclusive with body mass index (BMI) between 25.0 and 35.0 kg/m2 inclusive;
- •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 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 thiazolidinediones, dipeptidyl peptidase IV inhibitors ('gliptins'), glucagon-like peptide-1 (GLP-1) analogues, sodium-glucose co-transporter (SGLT-2) inhibitors, and insulin;
- •Subjects who have a history of relevant and severe atopy e.g. asthma, angioedema requiring emergency treatment, severe hayfever requiring regular treatment, severe eczema requiring regular treatment;
- •Subjects who have a history of relevant drug hypersensitivity;
- •Subjects who have a history of alcohol abuse or alcohol dependence according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria within the last two 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; monotherapy with sulphonylureas, or metformin. 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 G3215;
- •Subjects who are vegans or have any dietary restrictions;
- •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 (Sick, Control, One Stone, Fat, Food) questionnaires at screening.
研究组 & 干预措施
Placebo (B) - saline
5 subcutaneous injections of 0.9% saline, over a 4 week treatment period
干预措施: Placebo (Drug)
4 mg dose G3215 (A2) with varied formulation
4 mg G3215 single dose, subcutaneous injection
干预措施: G3215 (Drug)
12-24 mg (B1) dose of G3215
G3215 multiple dose, subcutaneous injection:
5 doses over a 4 week treatment period at escalating doses to a max of 24 mg.
干预措施: G3215 (Drug)
6-10 mg (B2) dose of G3215
G3215 multiple dose, subcutaneous injection:
5 doses over a 4 week treatment period at escalating doses to a max of 10 mg.
干预措施: G3215 (Drug)
5-16 mg (B3) dose of G3215
G3215 multiple dose, subcutaneous injection:
5 doses over a 4 week treatment period at escalating doses to a max of 16 mg.
干预措施: G3215 (Drug)
3.2mg (C) infusion pump dose of G3215
G3215 subcutaneous infusion over a 4 day treatment period at escalating doses to a max of 3.2 mg (with either the first or last day administering infusion of placebo [saline]).
干预措施: G3215 (Drug)
3.2mg (C) infusion pump dose of G3215
G3215 subcutaneous infusion over a 4 day treatment period at escalating doses to a max of 3.2 mg (with either the first or last day administering infusion of placebo [saline]).
干预措施: Placebo (Drug)
Placebo (A) - saline
Single subcutaneous injection of 0.9% saline
干预措施: Placebo (Drug)
0.1 mg dose G3215 (A1)
0.1 mg G3215 single dose, subcutaneous injection
干预措施: G3215 (Drug)
0.5 mg dose G3215 (A1)
0.5 mg G3215 single dose, subcutaneous injection
干预措施: G3215 (Drug)
1.5 mg dose G3215 (A1)
1.5 mg G3215 single dose, subcutaneous injection
干预措施: G3215 (Drug)
4 mg dose G3215 (A3) with varied formulation
4 mg G3215 single dose, subcutaneous injection
干预措施: G3215 (Drug)
4 mg dose G3215 (A4) with varied formulation
4 mg G3215 single dose, subcutaneous injection
干预措施: G3215 (Drug)
4 mg dose G3215 (A5) with varied formulation
4 mg G3215 single dose, subcutaneous injection
干预措施: G3215 (Drug)
8 mg dose G3215 (A7)
8 mg G3215 single dose, subcutaneous injection
干预措施: G3215 (Drug)
10 mg dose G3215 (A6)
10 mg G3215 single dose, subcutaneous injection
干预措施: G3215 (Drug)
12 mg dose G3215 (A8)
12 mg G3215 single dose, subcutaneous injection
干预措施: G3215 (Drug)
16 mg dose G3215 (A9)
16 mg G3215 single dose, subcutaneous injection
干预措施: G3215 (Drug)
32 mg dose G3215 (A10)
32 mg G3215 single dose, subcutaneous injection
干预措施: G3215 (Drug)
48 mg dose G3215 (A11)
48 mg G3215 single dose, subcutaneous injection
干预措施: G3215 (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 28 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
- Body Weight (Percentage Change From Baseline)(up to day 4 (am) for Part A, day 31 (pm) for Part B and day 5 (am) for Part C)