Back to results

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

Primary Purpose

Type2 Diabetes Mellitus

Status

Completed

Phase

Phase 2

Locations

India

Study Type

Interventional

Intervention

Insulin Tregopil

Insulin Aspart

About this trial

This is an interventional treatment trial for Type2 Diabetes Mellitus focused on measuring Oral insulin

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Diacon Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

Insulin Tregopil (IN-105) - 45mg

Insulin Tregopil (IN-105) - 30mg

Insulin Aspart

Arm Description

Strength of each tablet is 15mg

Pre-filled pen: 100 U/L

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Participants Achieving HbA1c < 7% (Part 1)

Number of participants achieving HbA1c < 7% at Week 12 and 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)]

Weight (Kgs) (Part 1)

Change from Baseline in weight (kgs) to 24 weeks

Lipid Profile (Part 1)

Change from Baseline in lipid profile (triglycerides, low-density lipoprotein, high-density lipoprotein, and total cholesterol) to 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.

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

Anti-drug Antibody Levels

Incidence and change from baseline in the relative levels of anti-drug antibody levels over 24 weeks

CGM

Area under the glucose curve below 70 mg/dL derived from CGM, applicable for only part II study

Full Information

NCT ID

NCT03430856

First Posted

November 17, 2017

Last Updated

May 1, 2020

Sponsor

Biocon Limited

1. Study Identification

Unique Protocol Identification Number

NCT03430856

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2020

Overall Recruitment Status

Completed

Study Start Date

December 26, 2017 (Actual)

Primary Completion Date

February 6, 2019 (Actual)

Study Completion Date

February 20, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Biocon Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type2 Diabetes Mellitus

Keywords

Oral insulin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Model Description

Study is conducted in two parts. Part I has 3 arms and Part 2 has 2 arms.

Masking

None (Open Label)

Masking Description

Open Label Trial

Allocation

Randomized

Enrollment

143 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Insulin Tregopil (IN-105) - 45mg

Arm Type

Experimental

Arm Description

Strength of each tablet is 15mg

Arm Title

Insulin Tregopil (IN-105) - 30mg

Arm Type

Experimental

Arm Description

Strength of each tablet is 15mg

Arm Title

Insulin Aspart

Arm Type

Active Comparator

Arm Description

Pre-filled pen: 100 U/L

Intervention Type

Drug

Intervention Name(s)

Insulin Tregopil

Other Intervention Name(s)

IN-105

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Insulin Aspart

Intervention Description

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

Primary Outcome Measure Information:

Title

Change From Baseline in HbA1c at 24 Weeks (Part 1)

Description

The primary endpoint is change from baseline in HbA1c after 24 weeks of randomized treatment.

Time Frame

Week 0, Week 24

Secondary Outcome Measure Information:

Title

Change From Baseline in HbA1c at Week 12 (Part 1)

Description

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.

Time Frame

Week 0, Week 12

Title

Participants Achieving HbA1c < 7% (Part 1)

Description

Number of participants achieving HbA1c < 7% at Week 12 and Week 24.

Time Frame

Week 12, Week 24

Title

Percentage of Participants With Hypoglycemia Events During 24-week Treatment Period (Part 1)

Description

Time Frame

Week 0 through Week 24

Title

Weight (Kgs) (Part 1)

Description

Change from Baseline in weight (kgs) to 24 weeks

Time Frame

Week 0 and Week 24

Title

Lipid Profile (Part 1)

Description

Change from Baseline in lipid profile (triglycerides, low-density lipoprotein, high-density lipoprotein, and total cholesterol) to 24 weeks

Time Frame

24 weeks

Title

Post-prandial Glucose (PPG) Excursion (Part 1)

Description

Change from Baseline in the mean 60, 90, 120 minutes PPG excursions assessed from standardized test meal at Week 24.

Time Frame

Week 0, Week 24

Title

Number of Participants With Treatment-Emergent Adverse Events (Part 1)

Description

Includes participants who have experienced at least one treatment emergent adverse events over 24 weeks

Time Frame

24 weeks

Title

Anti-drug Antibody Levels

Description

Incidence and change from baseline in the relative levels of anti-drug antibody levels over 24 weeks

Time Frame

24 weeks

Title

CGM

Description

Area under the glucose curve below 70 mg/dL derived from CGM, applicable for only part II study

Time Frame

24 weeks

Other Pre-specified Outcome Measures:

Title

Participants Achieving HbA1c < 7% Without Reported Clinically Significant or Severe Hypoglycemic Event Between End of Week 8 and Week 24

Description

Number of participants achieving HbA1c < 7% at Week 12 and Week 24 without reported clinically significant or severe hypoglycemic events between end of Week 8 and Week 24.

Time Frame

Week 12, Week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Subramanian Loganathan, MD

Organizational Affiliation

Biocon Research Limited

Official's Role

Study Director

Facility Information:

Facility Name

Diacon Hospital

City

Bangalore

State/Province

Karnataka

ZIP/Postal Code

560010

Country

India

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

36352762

Citation

Lebovitz HE, Fleming A, Cherrington AD, Joshi S, Athalye SN, Loganathan S, Vishweswaramurthy A, Panda J, Marwah A. Efficacy and safety of Tregopil, a novel, ultra-rapid acting oral prandial insulin analog, as part of a basal-bolus regimen in type 2 diabetes: a randomized, active-controlled phase 2/3 study. Expert Opin Pharmacother. 2022 Nov;23(16):1855-1863. doi: 10.1080/14656566.2022.2141569. Epub 2022 Nov 9.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs