Clinical trial NCT03430856: 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
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Type2 Diabetes Mellitus
Keywords: Oral insulin
Lead sponsor: Biocon Limited
Sponsor class: INDUSTRY
First posted: 2018-02-13
Enrollment: 143
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Study is conducted in two parts. Part I has 3 arms and Part 2 has 2 arms.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change From Baseline in HbA1c at 24 Weeks (Part 1)
timeFrame: Week 0, Week 24
Secondary outcomes:
measure: Change From Baseline in HbA1c at Week 12 (Part 1)
timeFrame: Week 0, Week 12
measure: Participants Achieving HbA1c < 7% (Part 1)
timeFrame: Week 12, Week 24
measure: Percentage of Participants With Hypoglycemia Events During 24-week Treatment Period (Part 1)
timeFrame: Week 0 through Week 24
measure: Weight (Kgs) (Part 1)
timeFrame: Week 0 and Week 24
measure: Lipid Profile (Part 1)
timeFrame: 24 weeks
measure: Post-prandial Glucose (PPG) Excursion (Part 1)
timeFrame: Week 0, Week 24
measure: Number of Participants With Treatment-Emergent Adverse Events (Part 1)
timeFrame: 24 weeks
measure: Anti-drug Antibody Levels
timeFrame: 24 weeks
measure: CGM
timeFrame: 24 weeks
Other outcomes:
measure: Participants Achieving HbA1c < 7% Without Reported Clinically Significant or Severe Hypoglycemic Event Between End of Week 8 and Week 24
timeFrame: Week 12, Week 24
Locations:
city: Bangalore
country: India
facility: Diacon Hospital
state: Karnataka
Study officials:
affiliation: Biocon Research Limited
name: Subramanian Loganathan, MD
role: STUDY_DIRECTOR
References:
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.