A Three-Part Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Subcutaneous Doses of HTL0030310 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Part 2 and Part 3 Maximum observed effect (EMax) 1) for insulin, glucose, glucagon, GLP1, C-peptide and GIP level 2) for GH 3) ACTH and cortisol
研究概览
简要总结
A Phase 1, first in human, three-part, single centre study to assess the safety, tolerability, PK and PD of single ascending subcutaneous doses of HTL0030310 in healthy subjects
详细描述
This is a first in human, three part study with the objective to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending subcutaneous doses of HTL0030310 in healthy subjects. Part 1 is a double-blind, placebo-controlled, randomised study assessing single ascending doses of HTL0030310. Part 2 is a site-blind (sponsor unblinded), placebo-controlled, part-randomised, fixed-sequence, single-dose, 4-period study assessing the PD of a positive control, pasireotide, following administration of challenge agents. Part 3 is a double-blind, placebo-controlled, part-randomised, fixed-sequence, single-dose, HTL0030310 proof of pharmacological effect study, where PD effects of HTL0030310 will be investigated following administration of challenge agents. The challenge agents administered in this study will be: oral glucose tolerance test (OGTT), Growth hormone-releasing hormone (GHRH), and corticotrophin releasing hormone (CRH) combined with desmopressin.
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)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Part 1 Single Ascending Dose
Eight subjects in up to 8 cohorts will be dosed. A single subcutaneous injection of HTL0030310 or placebo will be administered. In each cohort, 6 subjects will receive HTL0030310 and 2 subjects will receive placebo.
干预措施: HTL0030310 (Drug)
Part 1 Single Ascending Dose
Eight subjects in up to 8 cohorts will be dosed. A single subcutaneous injection of HTL0030310 or placebo will be administered. In each cohort, 6 subjects will receive HTL0030310 and 2 subjects will receive placebo.
干预措施: Placebo (Drug)
Part 2 Pasireotide PD Assessment
Sixteen subjects in 2 cohorts (8 subjects per cohort) will be dosed on 4 occasions. Within each cohort, 4 subjects will be randomised to active dosing with CRH with desmopressin, GHRH and OGTT challenge and 4 subjects will be randomised to placebo dosing with CRH with desmopressin, GHRH and OGTT challenge.
干预措施: Pasireotide (Drug)
Part 2 Pasireotide PD Assessment
Sixteen subjects in 2 cohorts (8 subjects per cohort) will be dosed on 4 occasions. Within each cohort, 4 subjects will be randomised to active dosing with CRH with desmopressin, GHRH and OGTT challenge and 4 subjects will be randomised to placebo dosing with CRH with desmopressin, GHRH and OGTT challenge.
干预措施: Placebo (Drug)
Part 3 Proof of Pharmacological Effect
Up to 80 subjects in 4 cohorts (up to 20 subjects per cohort) will be dosed in up to 3 study periods. In each period, subjects will receive active drug or placebo with GHRH, OGTT and CRH with desmopressin (optional).
干预措施: HTL0030310 (Drug)
Part 3 Proof of Pharmacological Effect
Up to 80 subjects in 4 cohorts (up to 20 subjects per cohort) will be dosed in up to 3 study periods. In each period, subjects will receive active drug or placebo with GHRH, OGTT and CRH with desmopressin (optional).
干预措施: Placebo (Drug)
结局指标
主要结局
Part 2 and Part 3 Maximum observed effect (EMax) 1) for insulin, glucose, glucagon, GLP1, C-peptide and GIP level 2) for GH 3) ACTH and cortisol
时间窗: Predose up to 4 hours post dose
Pharmacodynamics
Part 1: Number of treatment related adverse events (as determined by abnormal clinical laboratory tests, vitals signs, ECG parameters, Holter ECG parameters and injection site reactions)
时间窗: Admission up to 8 days post dose
Safety and Tolerability
Part 2 and Part 3 Area under the effect time curve (EAUC) 1) for insulin, glucose, glucagon, GLP1, C-peptide and GIP level 2) for GH 3) ACTH and cortisol
时间窗: Predose up to 4 hours post dose
Pharmacodynamics
Part 2 and Part 3 Time to reach Maximum observed effect (TEMax) 1) for insulin, glucose, glucagon, GLP1, C-peptide and GIP level 2) for GH 3) ACTH and cortisol
时间窗: Predose up to 4 hours post dose
Pharmacodynamics
次要结局
- Part 2 Time to reach Maximum observed plasma concentration (Tmax) of single subcutaneous doses of pasireotide(Predose to 24 hours postdose)
- Part 1 Area under the curve (AUC) of single subcutaneous doses of HTL0030310(Pre dose to 144 hours post dose)
- Part 3 Time to reach Maximum observed plasma concentration (Tmax) of single subcutaneous doses of HTL0030310(Predose to 96 hours postdose)
- Part 3 Area under the curve (AUC) of single subcutaneous doses of HTL0030310(Predose to 96 hours postdose)
- Part 1 Maximum observed plasma concentration (Cmax) of single subcutaneous doses of HTL0030310(Pre dose to 144 hours post dose)
- Part 1 Time to reach Maximum observed plasma concentration (Tmax) of single subcutaneous doses of HTL0030310(Pre dose to 144 hours post dose)
- Part 2 Maximum observed plasma concentration (Cmax) of single subcutaneous doses of pasireotide(Predose to 24 hours postdose)
- Part 3: Number of treatment related adverse events (as determined by abnormal clinical laboratory tests, vitals signs, ECG parameters and injection site reactions)(Admission up to 8 to 10 days post final dose)
- Part 2 Area under the curve (AUC) of single subcutaneous doses of pasireotide(Predose to 24 hours postdose)
- Part 3 Maximum observed plasma concentration (Cmax) of single subcutaneous doses of HTL0030310(Predose to 96 hours postdose)