Type2 Diabetes Mellitus
Conditions
Keywords
Oral insulin
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.
Interventions
DRUGInsulin Tregopil
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.
DRUGInsulin Aspart
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
Sponsors
Biocon Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label Trial
Intervention model description
Study is conducted in two parts. Part I has 3 arms and Part 2 has 2 arms.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c at 24 Weeks (Part 1) | Week 0, Week 24 | The primary endpoint is change from baseline in HbA1c after 24 weeks of randomized treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c at Week 12 (Part 1) | Week 0, Week 12 | 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) | Week 12, Week 24 | 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) | Week 0 through Week 24 | 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) | Week 0 and Week 24 | Change from Baseline in weight (kgs) to 24 weeks |
| Post-prandial Glucose (PPG) Excursion (Part 1) | Week 0, Week 24 | 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) | 24 weeks | Includes participants who have experienced at least one treatment emergent adverse events over 24 weeks |
| Anti-drug Antibody Levels | 24 weeks | Incidence and change from baseline in the relative levels of anti-drug antibody levels over 24 weeks |
| CGM | 24 weeks | Area under the glucose curve below 70 mg/dL derived from CGM, applicable for only part II study |
| Lipid Profile (Part 1) | 24 weeks | Change from Baseline in lipid profile (triglycerides, low-density lipoprotein, high-density lipoprotein, and total cholesterol) to 24 weeks |
Other
| Measure | Time frame | Description |
|---|---|---|
| Participants Achieving HbA1c < 7% Without Reported Clinically Significant or Severe Hypoglycemic Event Between End of Week 8 and Week 24 | Week 12, Week 24 | 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. |
Countries
India
Participant flow
Recruitment details
Out of 20 sites, which were selected for recruitment, 19 sites enrolled subjects in the run-in period, of which 15 sites later assigned subjects to randomized treatment: India:20 sites
Pre-assignment details
The trial included an 8-week run-in period and a 24-week treatment period. During the run-in period, the subjects received insulin glargine along with metformin. In total, 143 subjects entered the run-in period, of these 52 subjects were run-in failures. Hence, 91 subjects were randomly assigned to each treatment arm.
Participants by arm
| Arm | Count |
|---|---|
| Insulin Tregopil (IN-105) - 45mg At randomization, all subjects started on 45 mg mealtime insulin Tregopil (oral) in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose. | 31 |
| Insulin Tregopil (IN-105) - 30mg At randomization, all subjects started on 30 mg mealtime insulin Tregopil in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose. | 30 |
| Insulin Aspart At randomization, all subjects started on 4 units of mealtime insulin aspart (bolus insulin) in combination with insulin glargine (basal insulin, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin aspart was administered (sc) 0-5 minutes before each main meal, was titrated to the pre-prandial glycaemic target of 71-129 mg/dL and 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered daily based on the pre-prandial and 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose. | 30 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Rescue criteria | 1 | 1 | 0 |
| Overall Study | Voluntary withdrawal of consent | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Insulin Tregopil (IN-105) - 45mg | Insulin Tregopil (IN-105) - 30mg | Insulin Aspart |
|---|---|---|---|---|
| Active proliferative retinopathy, Yes or No No | 91 participants | 31 participants | 30 participants | 30 participants |
| Active proliferative retinopathy, Yes or No Yes | 0 participants | 0 participants | 0 participants | 0 participants |
| Age, Continuous | 52.5 Year STANDARD_DEVIATION 9.08 | 52.1 Year STANDARD_DEVIATION 9.49 | 50.9 Year STANDARD_DEVIATION 9.44 | 54.5 Year STANDARD_DEVIATION 8.18 |
| BMI | 27.22 kg/m^2 STANDARD_DEVIATION 3.618 | 27.13 kg/m^2 STANDARD_DEVIATION 3.866 | 27.39 kg/m^2 STANDARD_DEVIATION 3.418 | 27.13 kg/m^2 STANDARD_DEVIATION 3.667 |
| Duration of T2DM | 8.25 years STANDARD_DEVIATION 7.404 | 8.78 years STANDARD_DEVIATION 7.867 | 7.83 years STANDARD_DEVIATION 7.715 | 8.12 years STANDARD_DEVIATION 6.788 |
| Glycosylated haemoglobin A1c | 8.13 Percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.646 | 8.23 Percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.577 | 8.10 Percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.67 | 8.07 Percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.697 |
| Height | 158.60 cm STANDARD_DEVIATION 8.776 | 158.84 cm STANDARD_DEVIATION 7.987 | 158.76 cm STANDARD_DEVIATION 9.268 | 158.20 cm STANDARD_DEVIATION 9.321 |
| Metformin dose Number of participants (%) <1500 mg/day | 9 participants | 4 participants | 2 participants | 3 participants |
| Metformin dose Number of participants (%) >=1500 mg/day | 82 participants | 27 participants | 28 participants | 27 participants |
| OAD/Basal Insulin use at Screening Number of participants (%) Metformin alone | 6 Participants | 4 Participants | 2 Participants | 0 Participants |
| OAD/Basal Insulin use at Screening Number of participants (%) Metformin - OADs + Basal insulin | 10 Participants | 3 Participants | 3 Participants | 4 Participants |
| OAD/Basal Insulin use at Screening Number of participants (%) Metformin + OADs + Basal insulin | 56 Participants | 18 Participants | 19 Participants | 19 Participants |
| OAD/Basal Insulin use at Screening Number of participants (%) Metformin + other OADs | 19 Participants | 6 Participants | 6 Participants | 7 Participants |
| OAD use evaluated at screening Alpha Glucosidase Inhibitors | 9 participants | 2 participants | 3 participants | 4 participants |
| OAD use evaluated at screening Biguanides | 91 participants | 31 participants | 30 participants | 30 participants |
| OAD use evaluated at screening Blood Glucose Lowering Drugs, Excl. Insulins | 8 participants | 2 participants | 3 participants | 3 participants |
| OAD use evaluated at screening Combinations Of Oral Blood Glucose Lowering Drugs | 1 participants | 0 participants | 0 participants | 1 participants |
| OAD use evaluated at screening Dipeptidyl Peptidase 4 (Dpp-4) Inhibitors | 25 participants | 7 participants | 6 participants | 12 participants |
| OAD use evaluated at screening Other Blood Glucose Lowering Drugs, Excl. Insulins | 3 participants | 0 participants | 1 participants | 2 participants |
| OAD use evaluated at screening Sulfonylureas | 70 participants | 22 participants | 23 participants | 25 participants |
| OAD use evaluated at screening Thiazolidinediones | 10 participants | 2 participants | 2 participants | 6 participants |
| Other Abnormalities, Yes or No No | 74 participants | 23 participants | 24 participants | 27 participants |
| Other Abnormalities, Yes or No Yes | 17 participants | 8 participants | 6 participants | 3 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 91 Participants | 31 Participants | 30 Participants | 30 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment India | 91 participants | 31 participants | 30 participants | 30 participants |
| Sex: Female, Male Female | 43 Participants | 15 Participants | 14 Participants | 14 Participants |
| Sex: Female, Male Male | 48 Participants | 16 Participants | 16 Participants | 16 Participants |
| Weight | 68.39 kg STANDARD_DEVIATION 10.048 | 68.54 kg STANDARD_DEVIATION 11.559 | 68.88 kg STANDARD_DEVIATION 9.04 | 67.76 kg STANDARD_DEVIATION 9.628 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 5 / 31 | 5 / 30 | 4 / 30 |
| serious Total, serious adverse events | 0 / 31 | 0 / 30 | 0 / 30 |
Outcome results
Primary
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.
Time frame: Week 0, Week 24
Population: The analysis of this efficacy endpoint was based on the full analysis set (FAS). FAS included all randomized subjects in Part 1. The statistical evaluation of the FAS was to follow the intention-to-treat (ITT) principle and subjects contributed to the evaluation 'as randomized'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Tregopil (IN-105) - 45mg | Change From Baseline in HbA1c at 24 Weeks (Part 1) | Week 24 | 8.38 Percentage of glycosylated hemoglobin | Standard Deviation 1.139 |
| Insulin Tregopil (IN-105) - 45mg | Change From Baseline in HbA1c at 24 Weeks (Part 1) | Baseline (Week 0) | 8.23 Percentage of glycosylated hemoglobin | Standard Deviation 0.577 |
| Insulin Tregopil (IN-105) - 30mg | Change From Baseline in HbA1c at 24 Weeks (Part 1) | Baseline (Week 0) | 8.10 Percentage of glycosylated hemoglobin | Standard Deviation 0.67 |
| Insulin Tregopil (IN-105) - 30mg | Change From Baseline in HbA1c at 24 Weeks (Part 1) | Week 24 | 8.21 Percentage of glycosylated hemoglobin | Standard Deviation 0.969 |
| Insulin Aspart | Change From Baseline in HbA1c at 24 Weeks (Part 1) | Baseline (Week 0) | 8.07 Percentage of glycosylated hemoglobin | Standard Deviation 0.697 |
| Insulin Aspart | Change From Baseline in HbA1c at 24 Weeks (Part 1) | Week 24 | 7.29 Percentage of glycosylated hemoglobin | Standard Deviation 0.788 |
95% CI: [0.502, 1.47]
95% CI: [0.414, 1.37]
Secondary
Anti-drug Antibody Levels
Incidence and change from baseline in the relative levels of anti-drug antibody levels over 24 weeks
Time frame: 24 weeks
Population: This was planned for part 2 of the study. As part-2 of the study was discontinued, this is not applicable.
Secondary
CGM
Area under the glucose curve below 70 mg/dL derived from CGM, applicable for only part II study
Time frame: 24 weeks
Population: This was planned for part 2 of the study. As part-2 of the study was discontinued, this is not applicable.
Secondary
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.
Time frame: Week 0, Week 12
Population: This endpoint was summarized using ITT analysis set in Part I. ITT set included all randomized subjects. At Week 12, data from available participants are summarized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Tregopil (IN-105) - 45mg | Change From Baseline in HbA1c at Week 12 (Part 1) | Week 12 | 8.04 Percentage of glycosylated haemoglobin | Standard Deviation 0.94 |
| Insulin Tregopil (IN-105) - 45mg | Change From Baseline in HbA1c at Week 12 (Part 1) | Baseline (Week 0) | 8.23 Percentage of glycosylated haemoglobin | Standard Deviation 0.577 |
| Insulin Tregopil (IN-105) - 45mg | Change From Baseline in HbA1c at Week 12 (Part 1) | Change from Baseline | -0.17 Percentage of glycosylated haemoglobin | Standard Deviation 0.913 |
| Insulin Tregopil (IN-105) - 30mg | Change From Baseline in HbA1c at Week 12 (Part 1) | Week 12 | 8.01 Percentage of glycosylated haemoglobin | Standard Deviation 0.898 |
| Insulin Tregopil (IN-105) - 30mg | Change From Baseline in HbA1c at Week 12 (Part 1) | Baseline (Week 0) | 8.10 Percentage of glycosylated haemoglobin | Standard Deviation 0.67 |
| Insulin Tregopil (IN-105) - 30mg | Change From Baseline in HbA1c at Week 12 (Part 1) | Change from Baseline | -0.07 Percentage of glycosylated haemoglobin | Standard Deviation 0.866 |
| Insulin Aspart | Change From Baseline in HbA1c at Week 12 (Part 1) | Baseline (Week 0) | 8.07 Percentage of glycosylated haemoglobin | Standard Deviation 0.697 |
| Insulin Aspart | Change From Baseline in HbA1c at Week 12 (Part 1) | Change from Baseline | -0.88 Percentage of glycosylated haemoglobin | Standard Deviation 0.85 |
| Insulin Aspart | Change From Baseline in HbA1c at Week 12 (Part 1) | Week 12 | 7.18 Percentage of glycosylated haemoglobin | Standard Deviation 0.81 |
Secondary
Lipid Profile (Part 1)
Change from Baseline in lipid profile (triglycerides, low-density lipoprotein, high-density lipoprotein, and total cholesterol) to 24 weeks
Time frame: 24 weeks
Population: This was planned for part 2 of the study. As part-2 of the study was discontinued, this is not applicable.
Secondary
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
Time frame: 24 weeks
Population: This endpoint was summarized using Treatment Emergent Adverse Events - Safety Analysis Set (Part I).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Insulin Tregopil (IN-105) - 45mg | Number of Participants With Treatment-Emergent Adverse Events (Part 1) | 5 Participants |
| Insulin Tregopil (IN-105) - 30mg | Number of Participants With Treatment-Emergent Adverse Events (Part 1) | 6 Participants |
| Insulin Aspart | Number of Participants With Treatment-Emergent Adverse Events (Part 1) | 4 Participants |
Secondary
Participants Achieving HbA1c < 7% (Part 1)
Number of participants achieving HbA1c \< 7% at Week 12 and Week 24.
Time frame: Week 12, Week 24
Population: This endpoint was summarized using intention-to-treat (ITT) analysis set. ITT set included all randomized participants. At Week 12 and Week 24, data from available participants are summarized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Insulin Tregopil (IN-105) - 45mg | Participants Achieving HbA1c < 7% (Part 1) | Week 24 | 2 Participants |
| Insulin Tregopil (IN-105) - 45mg | Participants Achieving HbA1c < 7% (Part 1) | Week 12 | 4 Participants |
| Insulin Tregopil (IN-105) - 30mg | Participants Achieving HbA1c < 7% (Part 1) | Week 24 | 2 Participants |
| Insulin Tregopil (IN-105) - 30mg | Participants Achieving HbA1c < 7% (Part 1) | Week 12 | 3 Participants |
| Insulin Aspart | Participants Achieving HbA1c < 7% (Part 1) | Week 12 | 13 Participants |
| Insulin Aspart | Participants Achieving HbA1c < 7% (Part 1) | Week 24 | 10 Participants |
Secondary
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 \[mg/dL (3.9 millimoles/liter (mmol/L)\]
Time frame: Week 0 through Week 24
Population: This endpoint was summarized using safety analysis set in Part I. Safety analysis set included patients who were randomized and took at least 1 dose of the study drug. Patients in the safety analysis set contributed to the evaluation 'as treated'.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Insulin Tregopil (IN-105) - 45mg | Percentage of Participants With Hypoglycemia Events During 24-week Treatment Period (Part 1) | 26 Participants |
| Insulin Tregopil (IN-105) - 30mg | Percentage of Participants With Hypoglycemia Events During 24-week Treatment Period (Part 1) | 26 Participants |
| Insulin Aspart | Percentage of Participants With Hypoglycemia Events During 24-week Treatment Period (Part 1) | 25 Participants |
Secondary
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.
Time frame: Week 0, Week 24
Population: This endpoint was summarized using the intention-to-treat (ITT) analysis set from Part I. ITT set included all randomized participants. At Week 24, data from available participants are summarized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Tregopil (IN-105) - 45mg | Post-prandial Glucose (PPG) Excursion (Part 1) | Week 0, 60 min | 79.5 mg/dL | Standard Deviation 45.53 |
| Insulin Tregopil (IN-105) - 45mg | Post-prandial Glucose (PPG) Excursion (Part 1) | Week 0, 90 min | 92.4 mg/dL | Standard Deviation 47.94 |
| Insulin Tregopil (IN-105) - 45mg | Post-prandial Glucose (PPG) Excursion (Part 1) | Week 0, 120 min | 100.9 mg/dL | Standard Deviation 58.18 |
| Insulin Tregopil (IN-105) - 45mg | Post-prandial Glucose (PPG) Excursion (Part 1) | Week 24, 60 min | 35.8 mg/dL | Standard Deviation 44.26 |
| Insulin Tregopil (IN-105) - 45mg | Post-prandial Glucose (PPG) Excursion (Part 1) | Week 24, 90 min | 53.8 mg/dL | Standard Deviation 45.38 |
| Insulin Tregopil (IN-105) - 45mg | Post-prandial Glucose (PPG) Excursion (Part 1) | Week 24, 120 min | 64.1 mg/dL | Standard Deviation 51.87 |
| Insulin Tregopil (IN-105) - 30mg | Post-prandial Glucose (PPG) Excursion (Part 1) | Week 24, 120 min | 50.2 mg/dL | Standard Deviation 44.23 |
| Insulin Tregopil (IN-105) - 30mg | Post-prandial Glucose (PPG) Excursion (Part 1) | Week 0, 60 min | 98.3 mg/dL | Standard Deviation 41.94 |
| Insulin Tregopil (IN-105) - 30mg | Post-prandial Glucose (PPG) Excursion (Part 1) | Week 24, 60 min | 32.7 mg/dL | Standard Deviation 45.13 |
| Insulin Tregopil (IN-105) - 30mg | Post-prandial Glucose (PPG) Excursion (Part 1) | Week 24, 90 min | 47.2 mg/dL | Standard Deviation 44.84 |
| Insulin Tregopil (IN-105) - 30mg | Post-prandial Glucose (PPG) Excursion (Part 1) | Week 0, 90 min | 106.4 mg/dL | Standard Deviation 35.39 |
| Insulin Tregopil (IN-105) - 30mg | Post-prandial Glucose (PPG) Excursion (Part 1) | Week 0, 120 min | 113.5 mg/dL | Standard Deviation 53.45 |
| Insulin Aspart | Post-prandial Glucose (PPG) Excursion (Part 1) | Week 0, 90 min | 90.8 mg/dL | Standard Deviation 35.35 |
| Insulin Aspart | Post-prandial Glucose (PPG) Excursion (Part 1) | Week 0, 120 min | 93.7 mg/dL | Standard Deviation 41.2 |
| Insulin Aspart | Post-prandial Glucose (PPG) Excursion (Part 1) | Week 24, 120 min | 65.5 mg/dL | Standard Deviation 34.58 |
| Insulin Aspart | Post-prandial Glucose (PPG) Excursion (Part 1) | Week 24, 60 min | 55.1 mg/dL | Standard Deviation 34.57 |
| Insulin Aspart | Post-prandial Glucose (PPG) Excursion (Part 1) | Week 0, 60 min | 74.4 mg/dL | Standard Deviation 42.85 |
| Insulin Aspart | Post-prandial Glucose (PPG) Excursion (Part 1) | Week 24, 90 min | 66.3 mg/dL | Standard Deviation 36.13 |
Secondary
Weight (Kgs) (Part 1)
Change from Baseline in weight (kgs) to 24 weeks
Time frame: Week 0 and Week 24
Population: This endpoint was summarized using completed participants at Week 24 and all randomised participants at Week 0 in Part I. Change from baseline was summarised using completed participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Tregopil (IN-105) - 45mg | Weight (Kgs) (Part 1) | Week24 | 68.98 Kg | Standard Deviation 11.837 |
| Insulin Tregopil (IN-105) - 45mg | Weight (Kgs) (Part 1) | Baseline (Week 0) | 68.54 Kg | Standard Deviation 11.559 |
| Insulin Tregopil (IN-105) - 45mg | Weight (Kgs) (Part 1) | Change from Baseline | 0.93 Kg | Standard Deviation 1.212 |
| Insulin Tregopil (IN-105) - 30mg | Weight (Kgs) (Part 1) | Week24 | 70.15 Kg | Standard Deviation 8.915 |
| Insulin Tregopil (IN-105) - 30mg | Weight (Kgs) (Part 1) | Baseline (Week 0) | 68.88 Kg | Standard Deviation 9.04 |
| Insulin Tregopil (IN-105) - 30mg | Weight (Kgs) (Part 1) | Change from Baseline | 0.30 Kg | Standard Deviation 1.955 |
| Insulin Aspart | Weight (Kgs) (Part 1) | Baseline (Week 0) | 67.76 Kg | Standard Deviation 9.628 |
| Insulin Aspart | Weight (Kgs) (Part 1) | Change from Baseline | 0.66 Kg | Standard Deviation 1.807 |
| Insulin Aspart | Weight (Kgs) (Part 1) | Week24 | 68.47 Kg | Standard Deviation 9.761 |
Other Pre-specified
Participants Achieving HbA1c < 7% Without Reported Clinically Significant or Severe Hypoglycemic Event Between End of Week 8 and Week 24
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
Population: This endpoint was summarized using intention-to-treat (ITT) analysis set in Part I. ITT set included all randomized participants. At Week 12 and Week 24, data from available participant are summarized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Insulin Tregopil (IN-105) - 45mg | Participants Achieving HbA1c < 7% Without Reported Clinically Significant or Severe Hypoglycemic Event Between End of Week 8 and Week 24 | Week 12 | 4 Participants |
| Insulin Tregopil (IN-105) - 45mg | Participants Achieving HbA1c < 7% Without Reported Clinically Significant or Severe Hypoglycemic Event Between End of Week 8 and Week 24 | Week 24 | 1 Participants |
| Insulin Tregopil (IN-105) - 30mg | Participants Achieving HbA1c < 7% Without Reported Clinically Significant or Severe Hypoglycemic Event Between End of Week 8 and Week 24 | Week 12 | 3 Participants |
| Insulin Tregopil (IN-105) - 30mg | Participants Achieving HbA1c < 7% Without Reported Clinically Significant or Severe Hypoglycemic Event Between End of Week 8 and Week 24 | Week 24 | 3 Participants |
| Insulin Aspart | Participants Achieving HbA1c < 7% Without Reported Clinically Significant or Severe Hypoglycemic Event Between End of Week 8 and Week 24 | Week 12 | 11 Participants |
| Insulin Aspart | Participants Achieving HbA1c < 7% Without Reported Clinically Significant or Severe Hypoglycemic Event Between End of Week 8 and Week 24 | Week 24 | 7 Participants |