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

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 .

Inclusion criteria

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

Exclusion criteria

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

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

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

• Patients on OADs other than metformin for previous three months prior to screening.
• 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).
• 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.