To Assess the Pharmacokinetics and Pharmacodynamics of IN-105 in Relation to the Pre-meal Dosing Time, Between-meal Interval and Type of Meal - A Phase 1, Three Cohort, Randomized, Placebo Controlled, Crossover Trial in Type 2 Diabetes Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 51
- 主要终点
- Glucose AUC0-t will be assessed (Cohort 3)
研究概览
简要总结
A study to evaluate the PK and PD of oral IN-105 (Insulin Tregopil) w.r.t. time of dosing prior to meal, duration between meals and type of meal .
详细描述
A Phase 1, Randomized, Placebo Controlled, Crossover Trial in Type 2 Diabetes Patients to evaluate the effect of pre-meal dosing time, inter-meal interval and meal composition on the PK and PD of IN-105 (Insulin Tregopil), an oral insulin; conducted in 3 sequential cohorts in an adaptive manner .
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient should have an established diagnosis of T2DM per ADA 2013 criteria for at least 1 year prior to screening and are on metformin treatment for at least a month before screening.
- •Body mass index (BMI) of 18.5 to 40.00 kg/m2, both inclusive
- •Glycosylated hemoglobin (HbA1c) ≤ 9.5%.
- •Hemoglobin ≥9.0 g/dL.
- •No clinically significant abnormality in the ECG at screening.
- •Fasting plasma glucose levels less than 140 mg/dL at screening.
- •The patient should be ready to give a written and signed informed consent before starting any protocol-specific procedures.
排除标准
- •History of hypersensitivity to insulins or insulin analogues.
- •Evidence of the following (either due to improper diabetes control or due to secondary complications following diabetes).
- •History of ≥2 episodes of severe hypoglycemia within 6 months before screening or history of hypoglycemia unawareness as judged by the investigator.
- •History of ≥1 episodes of hyperglycemic hyperosmolar state or emergency room visits for uncontrolled diabetes leading to hospitalization in the 6 months prior to screening.
- •History of limb amputation as a complication of diabetes during his/her lifetime or any vascular procedure during the 1 year prior to screening.
- •History of diabetic foot or diabetic ulcers in the past 1 year prior to screening.
- •History of severe form of neuropathy or cardiac autonomic neuropathy (determined when obtaining patient history).
- •Presence of any of the following:
- •Serological evidence of human immunodeficiency virus (HIV), hepatitis B (HBsAg) or hepatitis C infection at screening.
- •Any clinically significant abnormality in the safety laboratory tests conducted at screening.
- •Impaired hepatic function at screening [alanine transaminase (ALT) or aspartate aminotransferase (AST) value >2 times the upper limit of the reference range and/or serum bilirubin 1.5 times the upper limit of the reference range] which investigator considers clinically significant.
- •Evidence of clinically significant chronic renal disease (e.g. nephrotic syndrome, diabetic nephropathy) as assessed by the investigator at screening
- •History or use of the following:
- •Patients on OADs other than metformin for previous three months prior to screening.
- •Patients who have received ≥14 consecutive days of oral, intravenous, or inhaled glucocorticoid therapy within the past 1 year or have received steroids by any route within 4 weeks immediately preceding screening visit (intra-nasal, intra ocular, and topical steroid use is allowed).
- •Receipt of another investigational drug in the 4 weeks prior to screening, or within 5 half-lives of the another investigational drug at screening visit (whichever is longer), or scheduled for another investigational drug during the current study period.
研究组 & 干预措施
IN-105 (Insulin Tregopil)
Cohort1: Treatments A, B, and C: IN-105 administered at 30, 20 or 10 minutes before the ADA meal, respectively; Treatment D: Placebo administered at 20 minutes before the ADA meal.
Cohort 2: Treatments A, B, and C: IN-105 administered at 4, 5, and 6 hours after the previous ADA meal, respectively; Treatments D, E, and F: Placebo administered at 4, 5, and 6 hours after the previous ADA meal, respectively.
Cohort 3: For the first meal, IN-105 30 mg administered at the optimal pre meal time determined from Cohort 1 with ADA meal (Treatments A and D) or high fat meal (Treatments B and E) or high fiber meal (Treatments C or F).
干预措施: IN-105 (Insulin Tregopil) (Drug)
Placebo tablet
Cohort1: Treatments A, B, and C: IN-105 administered at 30, 20 or 10 minutes before the ADA meal, respectively; Treatment D: Placebo administered at 20 minutes before the ADA meal.
Cohort 2: Treatments A, B, and C: IN-105 administered at 4, 5, and 6 hours after the previous ADA meal, respectively; Treatments D, E, and F: Placebo administered at 4, 5, and 6 hours after the previous ADA meal, respectively.
Cohort 3: For the first meal, IN-105 30 mg administered at the optimal pre meal time determined from Cohort 1 with ADA meal (Treatments A and D) or high fat meal (Treatments B and E) or high fiber meal (Treatments C or F).
干预措施: Placebo comparator (Other)
结局指标
主要结局
Glucose AUC0-t will be assessed (Cohort 3)
时间窗: time of dosing to 180 minutes post dose
Glucose AUC0-t \[AUC both above and below the baseline values\]
Area under the plasma concentration-time curve (AUC0-last) will be assessed (Cohort 1)
时间窗: from dosing time to 180 minutes post meal, extrapolated
Area under the plasma concentration-time curve (AUC0-last; from dosing time to 180 minutes post meal, extrapolated) after single dose administration in the 30 ,20 and 10 minute pre-meal dosing groups
The maximum observed plasma drug concentration (Cmax) will be assessed. (Cohort 2)
时间窗: time of dosing to 180 minutes post dose
The maximum observed plasma drug concentration after single dose administration (Cmax)
Glucose AUC0-t will be assessed (Cohort 2)
时间窗: time of dosing to 180 minutes post dose
Glucose AUC0-t \[AUC both above and below the baseline values\]
Glucose concentration (Tmin) will be assessed. (Cohort 3)
时间窗: time of dosing to 180 minutes post dose
Time of minimum observed glucose concentration (Tmin)
The maximum observed plasma drug concentration (Cmax) will be assessed (Cohort 1)
时间窗: from dosing time to 180 minutes post meal
The maximum observed plasma drug concentration after single dose administration (Cmax)
Glucose AUC0-t will be assessed (Cohort 1)
时间窗: from dosing time to 180 minutes post meal
Glucose AUC0-t \[AUC both above and below the baseline values\]
The maximum observed plasma drug concentration (Cmax) will be assessed (Cohort 3)
时间窗: time of dosing to 180 minutes post dose
The maximum observed plasma drug concentration after single dose administration (Cmax)
Glucose concentration (Cmin) will be assessed (Cohort 1)
时间窗: from dosing time to 180 minutes post meal
Minimum observed glucose concentration (Cmin)
Glucose concentration (Cmin) will be assessed (Cohort 2)
时间窗: time of dosing to 180 minutes post dose
Minimum observed glucose concentration (Cmin)
Area under the plasma concentration-time curve (AUC0-last) will be assessed (Cohort 3)
时间窗: time of dosing to 180 minutes post dose,extrapolated
Area under the plasma concentration-time curve (AUC0-last) for high-fat, high-fibre and ADA meal groups after single dose administration in morning and afternoon
Glucose concentration (Cmin) will be assessed. (Cohort 3)
时间窗: time of dosing to 180 minutes post dose
Minimum observed glucose concentration (Cmin)
Glucose concentration (Tmin) will be assessed (Cohort 1)
时间窗: from dosing time to 180 minutes post meal
Time of minimum observed glucose concentration (Tmin)
Area under the plasma concentration-time curve (AUC0-last) will be assessed (Cohort 2)
时间窗: time of dosing to 180 minutes post dose,extrapolated
Area under the plasma concentration-time curve (AUC0-last; time of dosing to 180 minutes post dose, extrapolated) after single dose administration in morning and afternoon in the 4, 5 and 6 h inter-meal interval groups.
Glucose concentration (Tmin) will be assessed (Cohort 2)
时间窗: time of dosing to 180 minutes post dose
Time of minimum observed glucose concentration (Tmin)
次要结局
- Number of Participants With Adverse Events as a Measure of Safety and Tolerability(Through study completion, approximately 3 months.)