An Open Label, Multiple Ascending Dose Trial in Patients With T1DM to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Insulin Tregopil and to Evaluate the Postprandial Glucose Control With Different Meal Types in Comparison With Insulin Aspart
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- Vital signs
研究概览
简要总结
Multi-centre, open label, multiple ascending dose trial in patients with type 1 diabetes mellitus
详细描述
This is a Phase 1, open-label, multiple dose trial with two parts in patients with type 1 diabetes mellitus (T1DM). Part 1 consists of four cohorts with multiple ascending doses of insulin Tregopil and comprises a sentinel dosing design. Part 2 consists of a randomised, 2-treatment, crossover design with mixed meal tests (MMTs) of different compositions followed by parallel design titrated treatment period. Both parts include dosing during an in-house period and during a subsequent outpatient period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Tregopil 30 mg
Dose level cohort with a sentinel dosing design
干预措施: Tregopil (Drug)
Tregopil 45 mg
Dose level cohort with a sentinel dosing design
干预措施: Tregopil (Drug)
Tregopil 60 mg
Dose level cohort with a sentinel dosing design
干预措施: Tregopil (Drug)
Derived Dose level
Derived Dose level cohort with a sentinel dosing design (60 mg fixed preprandial dose plus an additional 30 mg postprandial rescue dose, if required)
干预措施: Tregopil (Drug)
结局指标
主要结局
Vital signs
时间窗: Day of screening, Day1-6 and Day 20)
Number of patients with clinically significant changes in Vital signs (Part II)
Hyperglycaemia events
时间窗: Day of Run-in to Day 20 (Diary) and During follow up Via (Telephone)
Number of patients with Hyperglycaemia events (Part II)
Adverse events (AEs)
时间窗: Day of screening to Day 20 (Diary) and During follow up Via (Telephone)
Number of patients with Adverse Events (Part II)
Electrocardiograms
时间窗: Day of screening and Day 20
Number of patients with clinically significant changes in Electrocardiogram (ECG) (Part II)
Anti-insulin Tregopil antibodies
时间窗: Day -1 and Day 20
Change in antibody levels (Part II)
Laboratory safety parameters
时间窗: Day of screening and Day 20
Number of patients with clinically significant changes in Laboratory safety parameters (Part II)
Physical examination
时间窗: Day of screening, Dosing day 1 and Day 20
Number of patients with clinically significant changes in Physical examination (Part II)
Vital signs, clinically
时间窗: Between screening (up to Day -21) and End of study ( up to Day 6)
Number of patients with clinically significant changes in Vital signs (Part I)
Hypoglycaemic events
时间窗: Day of screening to Day 20 (Diary) and During follow up Via (Telephone)
Number of patients with Hypoglycaemia events (Part II)
次要结局
- PD Endpoints-minimum plasma glucose concentration in the indicated time intervals(0-6 hour)
- PK endpoint-terminal elimination half-life calculated(Day 1, Day 2, Day 6)
- PK endpoint-Area under the insulin concentration curve in the intended dosing interval (AUCins)(Day 1, Day 2, Day 6)
- Pharmacokinetics (PK) endpoint-Area under the insulin concentration curve(AUCins).(0 to 1 hour)
- PK endpoint-time to maximum observed insulin concentration (tmax)(Day 1, Day 2, Day 6)
- PK endpoint-Insulin concentration at the end of treatment (Ctrough)(Day 1, Day 2, Day 6)
- pharmacodynamics (PD) Endpoints-Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals on Day 1, 2 and 6 mixed meal tests(0-1 hour)
- PD Endpoints-Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals(0-6 hour)
- PD Endpoints-Area under the plasma glucose concentration curve in the indicated time intervals(0-6 hour)
- PK endpoint-Area under the insulin concentration curve(AUCins).(Day 1, Day 2, Day 6)
- PK endpoint-Insulin concentration in plasma, tlag (lag time)(Day 1, Day 2, Day 6)
- PK Endpoints- Maximum concentration recorded ( Day 1, 2,3,4,5,6,20)(0-4 hours)
- PK Endpoints-Area under the insulin concentration curve ( Day 1, 2,3,4,5,6,20)(0-∞)
- Duration of action;(0- 6 hour)
- PD Endpoints-maximal plasma glucose concentration in the indicated time intervals(0-6 hour)
- PD Endpoints-maximal plasma glucose observed sampling period(-10 min-6 hour)
- PD Endpoints- ΔGmin minimum postprandial plasma glucose increment, absolute and percent(0-6 hour)
- PD Endpoints- time to onset of action; time to decrease in PG of 5 mg/dL from baseline(0 hour)
- PD Endpoints-minimum plasma glucose concentration in the indicated time intervals ( Day 1, 2,3,4,5,6,20)(0-3 hours)
- Continuous glucose monitoring (CGM) profile(6 days)
- PK endpoint-time to maximum observed insulin concentration (tmax) ( Day 1, 2,3,4,5,6,20)(Day 1, Day 2,Day 3,Day 4, Day5, Day 6, Day 20)
- PK Endpoints-Area under the insulin concentration curve ( Day 1, 2,3,4,5,6, 20)(Day 1, Day 2,Day 3,Day 4, Day5, Day 6, Day 20)
- PK endpoint-Insulin concentration at the end of treatment ( Day 1, 2,3,4,5,6, 20)(Day 1, Day 2,Day 3,Day 4, Day5, Day 6, Day 20)
- PD Endpoints-Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals ( Day 1, 2,3,4,5,6, 20)(0-4 hours)
- PD Endpoints-Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals ( Day 1, 2,3,4,5,6,20)(0-6 hours)
- PD Endpoints-minimum plasma glucose concentration in the indicated time intervals ( Day 1, 2,3,4,5,6, 20)(0-4 hours)
- PK Endpoints- terminal elimination half-life calculated ( Day 1, 2,3,4,5,6,20)(Day 1, Day 2,Day 3,Day 4, Day5, Day 6, Day 20)
- PD Endpoints-maximal plasma glucose concentration in the indicated time intervals ( Day 1, 2,3,4,5,6, 20)(0-4 hours)
- PD Endpoints -minimal PG concentration in observed sampling period ( Day 1, 2,3,4,5,6, 20)(0 - 6 hours)
- PD Endpoints - maximal PG concentration in observed sampling period ( Day 1, 2,3,4,5,6, 20)(0 - 6 hours)
- PD Endpoints - CGM profile(Day 1 to 20)