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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03392961
• Other study ID #: IN-105-DM-01-G-14
• Status: Completed
• Phase: Phase 1
• First received: December 19, 2017
• Last updated: January 22, 2018
• Start date: March 27, 2014
• Est. completion date: July 1, 2014

Study information

• Verified date: January 2018
• Source: Biocon Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 .

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 .

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: July 1, 2014
• Est. primary completion date: July 1, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• IN-105 (Insulin Tregopil)
15 mg strength tablets for oral use used at a dose of 30 mg

Other:
• Placebo comparator
Placebo tablet for oral use

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Biocon Limited

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	Glucose concentration (Cmin) will be assessed (Cohort 1)	Minimum observed glucose concentration (Cmin)	from dosing time to 180 minutes post meal
Primary	Glucose concentration (Tmin) will be assessed (Cohort 1)	Time of minimum observed glucose concentration (Tmin)	from dosing time to 180 minutes post meal
Primary	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
Primary	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
Primary	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
Primary	Glucose concentration (Cmin) will be assessed (Cohort 2)	Minimum observed glucose concentration (Cmin)	time of dosing to 180 minutes post dose
Primary	Glucose concentration (Tmin) will be assessed (Cohort 2)	Time of minimum observed glucose concentration (Tmin)	time of dosing to 180 minutes post dose
Primary	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
Primary	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
Primary	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
Primary	Glucose concentration (Cmin) will be assessed. (Cohort 3)	Minimum observed glucose concentration (Cmin)	time of dosing to 180 minutes post dose
Primary	Glucose concentration (Tmin) will be assessed. (Cohort 3)	Time of minimum observed glucose concentration (Tmin)	time of dosing to 180 minutes post dose
Secondary	Number of Participants With Adverse Events as a Measure of Safety and Tolerability	An adverse event is any untoward medical event including hypoglycemia that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	Through study completion, approximately 3 months.