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

NCT03392961 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: IN-105-DM-01-G-14
• Study Type: interventional
• Target: 51
• Locations: 0 countries
• Sites: N/A

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 .

Conditions

Type 2 Diabetes Mellitus

Keywords

Oral insulin; Dosing time; Insulin concentration; Prandial insulin; Post Prandial Glucose (PPG)

Outcome Measures

Primary Outcomes (15)

• Area under the plasma concentration-time curve (AUC0-last) will be assessed (Cohort 1)

  Area under the plasma concentration-time curve (AUC0-last; from dosing time to 180 minutes post meal, extrapolated) after single dose administration in the 30 ,20 and 10 minute pre-meal dosing groups

  from dosing time to 180 minutes post meal, extrapolated

• The maximum observed plasma drug concentration (Cmax) will be assessed (Cohort 1)

  The maximum observed plasma drug concentration after single dose administration (Cmax)

  from dosing time to 180 minutes post meal

• Glucose AUC0-t will be assessed (Cohort 1)

  Glucose AUC0-t \[AUC both above and below the baseline values\]

  from dosing time to 180 minutes post meal

• Glucose concentration (Cmin) will be assessed (Cohort 1)

  Minimum observed glucose concentration (Cmin)

  from dosing time to 180 minutes post meal

• Glucose concentration (Tmin) will be assessed (Cohort 1)

  Time of minimum observed glucose concentration (Tmin)

  from dosing time to 180 minutes post meal

• Area under the plasma concentration-time curve (AUC0-last) will be assessed (Cohort 2)

  Area under the plasma concentration-time curve (AUC0-last; time of dosing to 180 minutes post dose, extrapolated) after single dose administration in morning and afternoon in the 4, 5 and 6 h inter-meal interval groups.

  time of dosing to 180 minutes post dose,extrapolated

• The maximum observed plasma drug concentration (Cmax) will be assessed. (Cohort 2)

  The maximum observed plasma drug concentration after single dose administration (Cmax)

  time of dosing to 180 minutes post dose

• Glucose AUC0-t will be assessed (Cohort 2)

  Glucose AUC0-t \[AUC both above and below the baseline values\]

  time of dosing to 180 minutes post dose

• Glucose concentration (Cmin) will be assessed (Cohort 2)

  Minimum observed glucose concentration (Cmin)

  time of dosing to 180 minutes post dose

• Glucose concentration (Tmin) will be assessed (Cohort 2)

  Time of minimum observed glucose concentration (Tmin)

  time of dosing to 180 minutes post dose

• Area under the plasma concentration-time curve (AUC0-last) will be assessed (Cohort 3)

  Area under the plasma concentration-time curve (AUC0-last) for high-fat, high-fibre and ADA meal groups after single dose administration in morning and afternoon

  time of dosing to 180 minutes post dose,extrapolated

• The maximum observed plasma drug concentration (Cmax) will be assessed (Cohort 3)

  The maximum observed plasma drug concentration after single dose administration (Cmax)

  time of dosing to 180 minutes post dose

• Glucose AUC0-t will be assessed (Cohort 3)

  Glucose AUC0-t \[AUC both above and below the baseline values\]

  time of dosing to 180 minutes post dose

• Glucose concentration (Cmin) will be assessed. (Cohort 3)

  Minimum observed glucose concentration (Cmin)

  time of dosing to 180 minutes post dose

• Glucose concentration (Tmin) will be assessed. (Cohort 3)

  Time of minimum observed glucose concentration (Tmin)

  time of dosing to 180 minutes post dose

Secondary Outcomes (1)

• Number of Participants With Adverse Events as a Measure of Safety and Tolerability

  Through study completion, approximately 3 months.

Study Arms (2)

IN-105 (Insulin Tregopil)

EXPERIMENTAL

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).

Drug: IN-105 (Insulin Tregopil)

Placebo tablet

PLACEBO COMPARATOR

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).

Other: Placebo comparator

Interventions

IN-105 (Insulin Tregopil) DRUG

15 mg strength tablets for oral use used at a dose of 30 mg

IN-105 (Insulin Tregopil)

Placebo comparator OTHER

Placebo tablet for oral use

Placebo tablet

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Biocon Limited: lead

Related Publications (1)

• 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.

  PMID: 31392840 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Juan Carlos Rondon, M.D,JD

  Elite Research Institute, 15705 NW 13th Avenue, Miami, Florida 33169

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: December 19, 2017
• First Posted: January 8, 2018
• Study Start: March 27, 2014
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: January 23, 2018

Record last verified: 2018-01