GPR119 Agonist for Hypoglycemia in Type 1 Diabetes

Phase 2

Completed

Conditions: Diabetes Mellitus, Type 1

Interventions: Drug: Placebo
Other: No medication for this group
Drug: Study Medication (MBX-2982)

Registration Number: NCT04432090

Lead Sponsor: AdventHealth Translational Research Institute

Brief Summary: The purpose of this study is to test if a specific research medication could increase the response to low blood glucose in people with type 1 diabetes. The response of the body to low blood sugar will be measured in healthy people as a reference point.

Detailed Description: This is a placebo-controlled, double-blinded, within-subject, cross-over phase 2a study. In randomized order, (Latin square, randomly assigned to placebo-active and active-placebo periods) and in a double-blinded manner, the participants with T1D received 14 days of daily dosing with MBX-2982 (or placebo), taken at the same time each day after breakfast. The last dose of treatment/placebo was given when the glucose tracer infusion for the euglycemic/hypoglycemic-glucose clamp started. Participants with T1D underwent two euglycemic-hypoglycemic clamps (induction of controlled hypoglycemia by an insulin infusion), using a within-subject cross-over design, with the two clamps separated by approximately four weeks, that is, two weeks of drug washout followed by two weeks of treatment with the alternative therapy. Glucagon, hepatic glucose production and other counter-regulatory hormonal responses were assessed during hypoglycemia. After completion of the first clamp study, participants did not receive any study medication for two weeks (washout phase) and then begin 14 days of the other arm (placebo or MBX-2982) in a double-blinded manner, followed by a repeat euglycemic-hypoglycemic clamp study. During treatment on each arm and during wash out phase, a blinded CGM was used to assess daily and nocturnal patterns of glycemia. On the day preceding a clamp study, while admitted to the research unit, a standardized meal test was used to assess fasting and postprandial glucagon, GLP-1 and GIP secretion. A healthy normal volunteer cohort with no diabetes was enrolled in the study for 14 days for comparison of normal responses to insulin induced hypoglycemia.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 110

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
MBX-2982 first then placebo- Volunteers with Type 1 diabetes	Placebo	Participants with type 1 diabetes (T1D) will be randomized to either study medication or placebo group. In this arm, participants will receive a pill that contains the study medication (MBX-2982). This will be followed by a wash-out period and a cross over to the second study period in which they will receive a pill that does not contain the medication (placebo).
MBX-2982 first then placebo- Volunteers with Type 1 diabetes	Study Medication (MBX-2982)	Participants with type 1 diabetes (T1D) will be randomized to either study medication or placebo group. In this arm, participants will receive a pill that contains the study medication (MBX-2982). This will be followed by a wash-out period and a cross over to the second study period in which they will receive a pill that does not contain the medication (placebo).
Healthy Volunteers	No medication for this group	This group will not receive any medication. It will be studied to establish the norm of the measurement that will be performed to obtain the study outcomes.
Placebo first then MBX-2982- Volunteers with Type 1 diabetes	Placebo	Participants with type 1 diabetes (T1D) will be randomized to either study medication or placebo group. In this arm, participants will receive a pill that does not contain the medication (placebo). This will be followed by a wash-out period and a cross over to the second study period in which they will receive a pill that contains the study medication (MBX-2982).
Placebo first then MBX-2982- Volunteers with Type 1 diabetes	Study Medication (MBX-2982)	Participants with type 1 diabetes (T1D) will be randomized to either study medication or placebo group. In this arm, participants will receive a pill that does not contain the medication (placebo). This will be followed by a wash-out period and a cross over to the second study period in which they will receive a pill that contains the study medication (MBX-2982).

Primary Outcome Measures

Name	Time	Method
Maximal Glucagon Concentration During Hypoglycemia	Day 14, Day 42	Maximal glucagon concentration during insulin induced hypoglycemia. This was measured during the hypoglycemic steady state of the hyper-insulinemic euglycemic-hypoglycemic clamp study.
Total Area Under the Curve (AUC) for Glucagon During Hypoglycemia.	Day 14, Day 42	This outcome was measured during the hypoglycemic steady state of the hyper-insulinemic euglycemic hypoglycemic clamp study. Total area under the curve (AUC) for glucagon was measured during the time points of 120 minutes to 140 minutes of the clamp.
Incremental AUC for Glucagon During Hypoglycemia (Above Baseline Levels During Euglycemia)	Day 14, Day 42	This is the difference between the AUC during the hypoglycemic steady state (time points 120 - 140 mins of clamp) and the baseline glucagon levels during euglycemic steady state (timepoints 60 min - 80 mins of the clamp)