Clinical trial NCT03392961: Effect of Dosing Time and Meal on IN-105 (Insulin Tregopil) PK and PD
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Keywords: Oral insulin
Dosing time
Insulin concentration
Prandial insulin
Post Prandial Glucose (PPG)
Lead sponsor: Biocon Limited
Sponsor class: INDUSTRY
First posted: 2018-01-08
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 3 Cohorts Cohort 1: 5 periods, 4 treatments and 5 sequences with a partial replicate crossover design Cohort 2: 6 periods, 6 treatments and 6 sequences in a cross-over design Cohort 3: 6 periods, 6 treatments and 6 sequences in a cross over design
Primary purpose: TREATMENT

Brief summary: 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 .

Detailed description: 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.

Primary outcomes:
measure: Area under the plasma concentration-time curve (AUC0-last) will be assessed (Cohort 1)
timeFrame: from dosing time to 180 minutes post meal, extrapolated
measure: The maximum observed plasma drug concentration (Cmax) will be assessed (Cohort 1)
timeFrame: from dosing time to 180 minutes post meal
measure: Glucose AUC0-t will be assessed (Cohort 1)
timeFrame: from dosing time to 180 minutes post meal
measure: Glucose concentration (Cmin) will be assessed (Cohort 1)
timeFrame: from dosing time to 180 minutes post meal
measure: Glucose concentration (Tmin) will be assessed (Cohort 1)
timeFrame: from dosing time to 180 minutes post meal
measure: Area under the plasma concentration-time curve (AUC0-last) will be assessed (Cohort 2)
timeFrame: time of dosing to 180 minutes post dose,extrapolated
measure: The maximum observed plasma drug concentration (Cmax) will be assessed. (Cohort 2)
timeFrame: time of dosing to 180 minutes post dose
measure: Glucose AUC0-t will be assessed (Cohort 2)
timeFrame: time of dosing to 180 minutes post dose
measure: Glucose concentration (Cmin) will be assessed (Cohort 2)
timeFrame: time of dosing to 180 minutes post dose
measure: Glucose concentration (Tmin) will be assessed (Cohort 2)
timeFrame: time of dosing to 180 minutes post dose
measure: Area under the plasma concentration-time curve (AUC0-last) will be assessed (Cohort 3)
timeFrame: time of dosing to 180 minutes post dose,extrapolated
measure: The maximum observed plasma drug concentration (Cmax) will be assessed (Cohort 3)
timeFrame: time of dosing to 180 minutes post dose
measure: Glucose AUC0-t will be assessed (Cohort 3)
timeFrame: time of dosing to 180 minutes post dose
measure: Glucose concentration (Cmin) will be assessed. (Cohort 3)
timeFrame: time of dosing to 180 minutes post dose
measure: Glucose concentration (Tmin) will be assessed. (Cohort 3)
timeFrame: time of dosing to 180 minutes post dose
Secondary outcomes:
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: Through study completion, approximately 3 months.
Other outcomes:
Locations:
Study officials:
affiliation: Elite Research Institute, 15705 NW 13th Avenue, Miami, Florida 33169
name: Juan Carlos Rondon, M.D,JD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Khedkar A, Lebovitz H, Fleming A, Cherrington A, Jose V, Athalye SN, Vishweswaramurthy A. Pharmacokinetics and Pharmacodynamics of Insulin Tregopil in Relation to Premeal Dosing Time, Between Meal Interval, and Meal Composition in Patients With Type 2 Diabetes Mellitus. Clin Pharmacol Drug Dev. 2020 Jan;9(1):74-86. doi: 10.1002/cpdd.730. Epub 2019 Aug 7.