Title
Effect of Dosing Time and Meal on IN-105 (Insulin Tregopil) PK and PD
To Assess the Pharmacokinetics and Pharmacodynamics of IN-105 in Relation to the Pre-meal Dosing Time, Between-meal Interval and Type of Meal - A Phase 1, Three Cohort, Randomized, Placebo Controlled, Crossover Trial in Type 2 Diabetes Patients
Phase
Phase 1Lead Sponsor
Biocon LimitedStudy Type
InterventionalStatus
Completed No Results PostedIndication/Condition
Type 2 Diabetes MellitusIntervention/Treatment
IN-105 (Insulin Tregopil) ...Study Participants
51A 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 .
15 mg strength tablets for oral use used at a dose of 30 mg
Placebo tablet for oral use
Cohort1: Treatments A, B, and C: IN-105 administered at 30, 20 or 10 minutes before the ADA meal, respectively; Treatment D: Placebo administered at 20 minutes before the ADA meal. Cohort 2: Treatments A, B, and C: IN-105 administered at 4, 5, and 6 hours after the previous ADA meal, respectively; Treatments D, E, and F: Placebo administered at 4, 5, and 6 hours after the previous ADA meal, respectively. Cohort 3: For the first meal, IN-105 30 mg administered at the optimal pre meal time determined from Cohort 1 with ADA meal (Treatments A and D) or high fat meal (Treatments B and E) or high fiber meal (Treatments C or F).
Cohort1: Treatments A, B, and C: IN-105 administered at 30, 20 or 10 minutes before the ADA meal, respectively; Treatment D: Placebo administered at 20 minutes before the ADA meal. Cohort 2: Treatments A, B, and C: IN-105 administered at 4, 5, and 6 hours after the previous ADA meal, respectively; Treatments D, E, and F: Placebo administered at 4, 5, and 6 hours after the previous ADA meal, respectively. Cohort 3: For the first meal, IN-105 30 mg administered at the optimal pre meal time determined from Cohort 1 with ADA meal (Treatments A and D) or high fat meal (Treatments B and E) or high fiber meal (Treatments C or F).
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.