Evaluation of Pharmacokinetics , Safety, Tolerability and Pharmacodynamics of Biocon Insulin Tregopil

Phase 1

Terminated

• Conditions: Type 1 Diabetes Mellitus (T1DM)
• Interventions: Drug: Tregopil

• Registration Number: NCT04141423
• Lead Sponsor: Biocon Limited

Brief Summary

Multi-centre, open label, multiple ascending dose trial in patients with type 1 diabetes mellitus

Detailed Description

This is a Phase 1, open-label, multiple dose trial with two parts in patients with type 1 diabetes mellitus (T1DM). Part 1 consists of four cohorts with multiple ascending doses of insulin Tregopil and comprises a sentinel dosing design. Part 2 consists of a randomised, 2-treatment, crossover design with mixed meal tests (MMTs) of different compositions followed by parallel design titrated treatment period. Both parts include dosing during an in-house period and during a subsequent outpatient period.

Study Timeline

• Study First Submitted: 2019-10-16
• Study First Submitted QC: 2019-10-25
• Study Start: 2019-10-28
• Study First Posted: 2019-10-28
• Primary Completion: 2021-04-23
• Study Completion: 2021-04-23
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-22
• Last Update Posted: 2022-06-27

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 55

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Tregopil 30 mg	Tregopil	Dose level cohort with a sentinel dosing design
Tregopil 45 mg	Tregopil	Dose level cohort with a sentinel dosing design
Tregopil 60 mg	Tregopil	Dose level cohort with a sentinel dosing design
Derived Dose level	Tregopil	Derived Dose level cohort with a sentinel dosing design (60 mg fixed preprandial dose plus an additional 30 mg postprandial rescue dose, if required)

Primary Outcome Measures

Name	Time	Method
Vital signs	Day of screening, Day1-6 and Day 20)	Number of patients with clinically significant changes in Vital signs (Part II)
Adverse events (AEs)	Day of screening to Day 20 (Diary) and During follow up Via (Telephone)	Number of patients with Adverse Events (Part II)
Electrocardiograms	Day of screening and Day 20	Number of patients with clinically significant changes in Electrocardiogram (ECG) (Part II)
Anti-insulin Tregopil antibodies	Day -1 and Day 20	Change in antibody levels (Part II)
Laboratory safety parameters	Day of screening and Day 20	Number of patients with clinically significant changes in Laboratory safety parameters (Part II)
Physical examination	Day of screening, Dosing day 1 and Day 20	Number of patients with clinically significant changes in Physical examination (Part II)
Vital signs, clinically	Between screening (up to Day -21) and End of study ( up to Day 6)	Number of patients with clinically significant changes in Vital signs (Part I)
Hypoglycaemic events	Day of screening to Day 20 (Diary) and During follow up Via (Telephone)	Number of patients with Hypoglycaemia events (Part II)
Hyperglycaemia events	Day of Run-in to Day 20 (Diary) and During follow up Via (Telephone)	Number of patients with Hyperglycaemia events (Part II)

Secondary Outcome Measures

Name	Time	Method
PD Endpoints-minimum plasma glucose concentration in the indicated time intervals	0-6 hour	Minimum plasma glucose concentration in the indicated time intervals (Part I)
PK endpoint-terminal elimination half-life calculated	Day 1, Day 2, Day 6	Terminal elimination half-life calculated as t½=ln2/ λz (Part I)
PK endpoint-Area under the insulin concentration curve in the intended dosing interval (AUCins)	Day 1, Day 2, Day 6	Area under the insulin concentration curve in the intended dosing interval (Part I)
Pharmacokinetics (PK) endpoint-Area under the insulin concentration curve(AUCins).	0 to 1 hour	Area under the insulin concentration curve (Part I)
PK endpoint-time to maximum observed insulin concentration (tmax)	Day 1, Day 2, Day 6	Time to maximum observed insulin concentration (Part I)
PK endpoint-Insulin concentration at the end of treatment (Ctrough)	Day 1, Day 2, Day 6	Insulin concentration at the end of treatment (Part I)
pharmacodynamics (PD) Endpoints-Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals on Day 1, 2 and 6 mixed meal tests	0-1 hour	Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals (Part I)
PD Endpoints-Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals	0-6 hour	Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals (Part I)
PD Endpoints-Area under the plasma glucose concentration curve in the indicated time intervals	0-6 hour	Area under the plasma glucose concentration curve in the indicated time intervals (Part I)
PK endpoint-Area under the insulin concentration curve(AUCins).	Day 1, Day 2, Day 6	AUC from time zero to infinity (Part I)
PK endpoint-Insulin concentration in plasma, tlag (lag time)	Day 1, Day 2, Day 6	Time to first appearance of insulin concentration in plasma after dosing (Part I)
PK Endpoints- Maximum concentration recorded ( Day 1, 2,3,4,5,6,20)	0-4 hours	Maximum concentration recorded (Cmax) (Part II)
PK Endpoints-Area under the insulin concentration curve ( Day 1, 2,3,4,5,6,20)	0-∞	Area under the insulin concentration curve (AUC) (Part II)
PD Endpoints-maximal plasma glucose concentration in the indicated time intervals	0-6 hour	Maximal plasma glucose concentration in the indicated time intervals (Part I)
PD Endpoints-maximal plasma glucose observed sampling period	-10 min-6 hour	maximal plasma glucose observed sampling period (Part I)
PD Endpoints- ΔGmin minimum postprandial plasma glucose increment, absolute and percent	0-6 hour	Minimum postprandial plasma glucose increment, absolute and percent (Part I)
PD Endpoints- time to onset of action; time to decrease in PG of 5 mg/dL from baseline	0 hour	Onset of action; time to decrease in PG of 5 mg/dL from baseline (Part I)
Duration of action;	0- 6 hour	time from onset of action to increase in PG ≥ 180 mg/dL post meal or time to increase to baseline PG if baseline \> 180 mg/dL (Part I)
Continuous glucose monitoring (CGM) profile	6 days	daily glycaemic control assessed d by mean (SD) glucose levels, percentage of time in normal range \[70-180 mg/dL\], percentage of time in hyperglycaemia range \[\>180 mg/dL\], percentage of time in hypoglycaemic range (\<70 mg/dL), percentage of readings in the range of 70-180 mg/dL (3.9- 10.0 mmol/L) per unit of time (Part I)
PK endpoint-time to maximum observed insulin concentration (tmax) ( Day 1, 2,3,4,5,6,20)	Day 1, Day 2,Day 3,Day 4, Day5, Day 6, Day 20	Time to maximum observed insulin concentration (Part II)
PK Endpoints-Area under the insulin concentration curve ( Day 1, 2,3,4,5,6, 20)	Day 1, Day 2,Day 3,Day 4, Day5, Day 6, Day 20	Area under the insulin concentration curve (AUC) (Part II)
PK endpoint-Insulin concentration at the end of treatment ( Day 1, 2,3,4,5,6, 20)	Day 1, Day 2,Day 3,Day 4, Day5, Day 6, Day 20	Insulin concentration at the end of treatment (Ctrough) (Part II)
PD Endpoints-Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals ( Day 1, 2,3,4,5,6, 20)	0-4 hours	Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals (GAUC) (Part II)
PD Endpoints-Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals ( Day 1, 2,3,4,5,6,20)	0-6 hours	Area under the plasma glucose concentration excursion from baseline (pre-meal) in the indicated time intervals (GExc) (Part II)
PD Endpoints-minimum plasma glucose concentration in the indicated time intervals ( Day 1, 2,3,4,5,6, 20)	0-4 hours	Minimum plasma glucose concentration in the indicated time intervals (Gmin) (Part II)
PK Endpoints- terminal elimination half-life calculated ( Day 1, 2,3,4,5,6,20)	Day 1, Day 2,Day 3,Day 4, Day5, Day 6, Day 20	Terminal elimination half-life calculated as t½=ln2/ λz (Part II)
PD Endpoints-minimum plasma glucose concentration in the indicated time intervals ( Day 1, 2,3,4,5,6,20)	0-3 hours	Minimum plasma glucose concentration in the indicated time intervals (Gmin) (Part II)
PD Endpoints-maximal plasma glucose concentration in the indicated time intervals ( Day 1, 2,3,4,5,6, 20)	0-4 hours	Maximal plasma glucose concentration in the indicated time intervals (Gmax) (Part II)
PD Endpoints -minimal PG concentration in observed sampling period ( Day 1, 2,3,4,5,6, 20)	0 - 6 hours	minimal PG concentration in observed sampling period (Part II)
PD Endpoints - maximal PG concentration in observed sampling period ( Day 1, 2,3,4,5,6, 20)	0 - 6 hours	maximal PG concentration in observed sampling period (Part II)
PD Endpoints - CGM profile	Day 1 to 20	CGM profile

Trial Locations

Locations (1)

Profil Mainz GmbH & Co. KG Malakoff-Passage,Rheinstraße 4C D-55116; 🇩🇪 Mainz, Germany