Samba-01: A Phase 1/2 Trial Investigating the Pharmacokinetics, Pharmacodynamics and Safety of Inhaled Insulin in Subjects With Type 1 Diabetes
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 主要终点
- Area under the insulin human / insulin lispro concentration-time curve from 0 to 8 hours (AUCINS,0-8h)
研究概览
简要总结
The purpose of this study was to compare the pharmacokinetic (PK) response after inhaled insulin administration with 3 different inhalation regimens and with subcutaneous insulin administration.
详细描述
This first-in-human trial investigated the optimal particle size for absorption of Dance-501, an aerosolized liquid human insulin for inhalation (INH).
Twelve subjects with type 1 diabetes received an INH dose (50 IU) using an inhaler on 4 visits and 6 U insulin lispro (LIS) sc on a separate visit to assess relative bioavailability (FREL) of INH. The inhaler was configured to generate insulin aerosol particles sized 3.5-4.0 μm (low output mesh; LOM), 4.3-4.8 μm (medium output mesh; MOM) or 5.0-5.5 μm (high output mesh; HOM) during low inspiratory flow. To assess within subject variability, MOM was used twice. Pharmacokinetics (PK) were measured up to 8 hours after dosing.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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
- •Type 1 diabetes mellitus treated with multiple daily insulin injections or continuous subcutaneous insulin infusion and total daily insulin dose less than 1.2 units/kg/day.
- •Body mass index 18.0 - 28.0 kg/m
- •Hemoglobin A1c less than or equal to 9%.
- •Forced vital capacity and forced expiratory volume in one second at least 75% of predicted normal values for race, age, gender and height.
- •Fasting C-peptide less than 0.3 nmol/L.
排除标准
- •Subjects with any condition possibly affecting drug absorption from the lung, in particular subjects with decreased lung function or subjects taking bronchodilators or subjects who smoke.
- •Active or chronic pulmonary disease.
- •Any clinically significant major disorders other than diabetes mellitus.
- •Decompensated heart failure at any time or angina pectoris within the last 12 months or acute myocardial infarction at any time.
- •Proliferative retinopathy or severe neuropathy.
研究组 & 干预措施
Inhaled insulin (LOM)
single 50 unit dose of Dance inhaled insulin administered using the Adagio-01 inhaler device with a low output mesh (aerosol particles sized 3.5-4.0 μm)
干预措施: inhaled human insulin (INH) (Drug)
Inhaled insulin (MOM1)
single 50 unit dose of Dance inhaled insulin administered using the Adagio-01 inhaler device with a medium output mesh (aerosol particles sized 4.3-4.8 μm)
干预措施: inhaled human insulin (INH) (Drug)
Inhaled insulin (MOM2)
repeat of single 50 unit dose of Dance inhaled insulin administered using the Adagio-01 inhaler device with a medium output mesh (aerosol particles sized 4.3-4.8 μm)
干预措施: inhaled human insulin (INH) (Drug)
Inhaled insulin (HOM)
single 50 unit dose of Dance inhaled insulin administered using the Adagio-01 inhaler device with a high output mesh (aerosol particles sized 5.0-5.5 μm)
干预措施: inhaled human insulin (INH) (Drug)
subcutaneous insulin lispro (LIS)
single 6 unit dose of insulin lispro administered subcutaneously
干预措施: sc insulin lispro (LIS) (Drug)
结局指标
主要结局
Area under the insulin human / insulin lispro concentration-time curve from 0 to 8 hours (AUCINS,0-8h)
时间窗: 0 to 8 hours
Bioavailability
时间窗: 0 to 8 hours
Relative delivery efficiency (FREL) of inhaled human insulin (INH) compared to s.c. injected insulin lispro (LIS)
次要结局
未报告次要终点