Comparison of Insulin Tregopil (IN-105) With Insulin Aspart in Type 2 Diabetes Mellitus Patients

Study Overview
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Brief Summary
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This is an open label Phase II/III study to evaluate the efficacy and safety of test drug, Insulin Tregopil (IN-105) compared with Insulin Aspart (IAsp) in Type 2 Diabetes Mellitus patients. on stable dose of Metformin and insulin Glargine. The study will be conducted in 2 parts, Part I and Part II. The study duration will be approximately 37 weeks for Part I and for Part II of the study respectively

Detailed Description
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Part I of the study is a Phase II multi-center, randomized, open label clinical study to evaluate the efficacy and safety of Insulin Tregopil (2 dose levels: 30 mg, 45 mg) compared with IAsp in the treatment of T2DM patients. Part II of the study is the Phase III, multi-center, randomized, open label clinical study to evaluate the efficacy and safety of Insulin Tregopil (30 mg or 45 mg based upon the outcome of Part I data) compared with IAsp in the treatment of T2DM patients. For Part I and Part II, the study duration will be approximately 37 weeks (3 weeks Screening, 8 weeks Run-in, 24 weeks Treatment, 2 weeks Safety follow-up). An Independent Data and Safety Monitoring Board (DSMB) will evaluate the data from Part I of the study. Part II of the study will be initiated after approval from the office of Drugs Controller General of India (DCGI) and Data Safety Monitoring Board (DSMB) recommendation based on review of data from Part I of the study. In both Part I and Part II of the study, T2DM patients with glycated hemoglobin (HbA1c) 7.5 to 10% (both inclusive), on stable dose of metformin ± oral antidiabetic drugs (OADs) ± basal insulin who are eligible for insulin glargine administration as per investigator discretion and who satisfy the selection criteria will be enrolled. The eligible patients will go through a Run-in period of 8 weeks. At the end of 8 weeks Run-in period, eligibility will be checked and patients will enter the treatment period of 24 weeks and will be allocated to 3 treatment arms (Part I) or randomized to 2 treatment arms (Part II); if found eligible for randomization. A total of 90 patients in part 1 and 268 patients in part 2 will be randomised to the treatment arms from approximately 40 centers in India.

Official Title
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An Open Label, Multi-center, Randomized, Parallel Group Phase II/III Clinical Study to Evaluate the Efficacy and Safety of Insulin Tregopil (IN-105) Compared With Insulin Aspart in the Treatment of Patients With Type 2 Diabetes Mellitus on Stable Dose of Metformin and Insulin Glargine

Conditions
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Type2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Insulin Tregopil
* Drug: Insulin Aspart


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria Patients with an established diagnosis of T2DM and a duration of diabetes mellitus of at least 6 months at Screening based on criteria given below as per American Diabetes Association (ADA) 2017 guidelines: i. HbA1c ≥ 6.5% OR ii. FPG ≥ 126 mg/dL. (Fasting is defined as no caloric intake for at least 8 hours.) OR iii. 2-hour prandial glucose (PG) level of ≥ 200 mg/dL during an oral glucose tolerance test (OGTT). Stable dose of metformin (at least 1500 mg daily [daily dose of at least 1000 mg is permitted if intolerant to 1500 mg dose]) for a period of at least 3 months prior to Screening Eligible for initiation of or already receiving insulin glargine Hemoglobin ≥ 10.0 g/Dl HbA1c of 7.5% to 10.0 % Body mass index of 18.5 to 35.0 kg/m2 Key Exclusion Criteria Patients with T1DM Treatment with glucagon-like peptide 1 agonists within 12 weeks prior to Screening Ongoing treatment with OADs (eg, Thiazolidinediones) contraindicated or unapproved for combination treatment with insulin Presence of gastrointestinal (GI) disorders or conditions known to significantly alter the absorption of orally administered drugs or significantly alter upper GI or pancreatic function History of ≥2 episodes of severe hypoglycemia (as per ADA 2017) within the 6 months before Screening History of > 1 episode of hyperglycemic hyperosmolar coma or hospitalization for uncontrolled diabetes (eg, diabetic ketoacidosis); within the 6 months prior to Screening Clinically significant cardiovascular and/or cerebrovascular disease within 12 months before Screening including, but not limited to unstable angina, myocardial infarction, Class III or Class IV congestive heart failure according to the New York Heart Association criteria, valvular heart disease, cardiac arrhythmia requiring treatment, pulmonary hypertension, cardiac surgery, coronary angioplasty, stroke or transient ischemic attack. Patients with the following secondary complications of diabetes: i. Active proliferative retinopathy as confirmed by a dilated ophthalmoscopy (by the investigator, site ophthalmologist or an optometrist; as per standard site practice) within 6 months prior to Screening. ii. Renal dysfunction indicated by modification of diet in renal disease estimated glomerular filtration rate < 45 mL/min/1.73 m2 and/or diabetic nephropathy and/or clinical nephrotic syndrome at Screening. iii. History or presence of severe form of neuropathy or signs and symptoms of severe cardiac autonomic neuropathy. iv. Patients with non-traumatic amputation (at any time) or clinically significant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Study is conducted in two parts. Part I has 3 arms and Part 2 has 2 arms.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin Tregopil (IN-105) - 45mg<br>Strength of each tablet is 15mg | Drug: Insulin Tregopil<br>* Drug: Insulin Tregopil (IN-105) Mode of Administration: To be administered orally 10 ± 2 minutes prior to each major meal (breakfast, lunch and dinner) starting at the Randomization visit.<br>* Other names: IN-105;|
| Experimental: Insulin Tregopil (IN-105) - 30mg<br>Strength of each tablet is 15mg | Drug: Insulin Tregopil<br>* Drug: Insulin Tregopil (IN-105) Mode of Administration: To be administered orally 10 ± 2 minutes prior to each major meal (breakfast, lunch and dinner) starting at the Randomization visit.<br>* Other names: IN-105;|
| Active Comparator: Insulin Aspart<br>Pre-filled pen: 100 U/L | Drug: Insulin Aspart<br>* Drug: Insulin Aspart Mode of Administration: To be administered within 5 minutes prior to each major meal (breakfast, lunch and dinner) starting at the Randomization visit<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c at 24 Weeks (Part 1) | The primary endpoint is change from baseline in HbA1c after 24 weeks of randomized treatment. | Week 0, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c at Week 12 (Part 1) | This secondary outcome is the change from baseline in HbA1c after 12 weeks of randomized treatment. For this endpoint baseline (Week 0) and Week 12 have been presented. | Week 0, Week 12 | 
| Participants Achieving HbA1c < 7% (Part 1) | Number of participants achieving HbA1c < 7% at Week 12 and Week 24. | Week 12, Week 24 | 
| Percentage of Participants With Hypoglycemia Events During 24-week Treatment Period (Part 1) | A hypoglycemic episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has blood glucose concentration of ≤ 70 milligrams/deciliter [mg/dL (3.9 millimoles/liter (mmol/L)] | Week 0 through Week 24 | 
| Weight (Kgs) (Part 1) | Change from Baseline in weight (kgs) to 24 weeks | Week 0 and Week 24 | 
| Lipid Profile (Part 1) | Change from Baseline in lipid profile (triglycerides, low-density lipoprotein, high-density lipoprotein, and total cholesterol) to 24 weeks | 24 weeks | 
| Post-prandial Glucose (PPG) Excursion (Part 1) | Change from Baseline in the mean 60, 90, 120 minutes PPG excursions assessed from standardized test meal at Week 24. | Week 0, Week 24 | 
| Number of Participants With Treatment-Emergent Adverse Events (Part 1) | Includes participants who have experienced at least one treatment emergent adverse events over 24 weeks | 24 weeks | 
| Anti-drug Antibody Levels | Incidence and change from baseline in the relative levels of anti-drug antibody levels over 24 weeks | 24 weeks | 
| CGM | Area under the glucose curve below 70 mg/dL derived from CGM, applicable for only part II study | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oral insulin