Effect of Dosing Time and Meal on IN-105 (Insulin Tregopil) PK and PD

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 .

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 .

Eligibility Criteria:
Inclusion Criteria:

1. 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.
2. Body mass index (BMI) of 18.5 to 40.00 kg/m2, both inclusive
3. Glycosylated hemoglobin (HbA1c) ≤ 9.5%.
4. Hemoglobin ≥9.0 g/dL.
5. No clinically significant abnormality in the ECG at screening.
6. Fasting plasma glucose levels less than 140 mg/dL at screening.
7. The patient should be ready to give a written and signed informed consent before starting any protocol-specific procedures.

Exclusion Criteria:

1. History of hypersensitivity to insulins or insulin analogues.
2. Evidence of the following (either due to improper diabetes control or due to secondary complications following diabetes).

   1. History of ≥2 episodes of severe hypoglycemia within 6 months before screening or history of hypoglycemia unawareness as judged by the investigator.
   2. 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.
   3. History of limb amputation as a complication of diabetes during his/her lifetime or any vascular procedure during the 1 year prior to screening.
   4. History of diabetic foot or diabetic ulcers in the past 1 year prior to screening.
   5. History of severe form of neuropathy or cardiac autonomic neuropathy (determined when obtaining patient history).
3. Presence of any of the following:

   1. Serological evidence of human immunodeficiency virus (HIV), hepatitis B (HBsAg) or hepatitis C infection at screening.
   2. Any clinically significant abnormality in the safety laboratory tests conducted at screening.
   3. 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.
   4. Evidence of clinically significant chronic renal disease (e.g. nephrotic syndrome, diabetic nephropathy) as assessed by the investigator at screening
4. History or use of the following:

   1. Patients on OADs other than metformin for previous three months prior to screening.
   2. 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).
5. 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.