A Study of LY3532226 in Participants With Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the response of glucagon to insulin-induced low blood sugar after administration of the study drug LY3532226 in participants with type 1 diabetes mellitus (T1DM). The study will also evaluate if LY3532226 helped participants to recover from insulin-induced low blood sugar condition compared to placebo. The study will last approximately 16 weeks excluding screening period.

Official Title
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A Phase 1, Randomized, Placebo-Controlled, 2-Period, Cross-over, Double- Blind, Single-Dose Study to Evaluate the Effects of LY3532226 on Insulin- Induced Hypoglycemia in Participants With Type 1 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: LY3532226
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with type 1 diabetes mellitus (T1DM) for at least 2 years treated with insulin Body mass index (BMI) of 18.5 to 40.0 kilograms per meter squared (kg/m²) Are males or females not of childbearing potential Exclusion Criteria: Have acute proliferative retinopathy requiring active treatment within 3 months of screening Have been treated with dipeptidyl peptidase-Ni, GLP-1 receptor agonists, GIP agonists, metformin or sodium-glucose cotransporter 2 inhibitors within the previous 3 months Have received systemic or inhaled glucocorticoid therapy Women of childbearing potential Are currently taking part in another clinical study trial involving medical research, or have participated within the last 30 days of screening in a clinical study involving a study intervention

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3532226<br> | Drug: LY3532226<br>* Administered subcutaneously (SC).<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Administered SC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics (PD): Area under the concentration versus time curve from time 60 to 120 minutes (AUC60-120min) of plasma glucagon during the insulin-induced hypoglycemia | PD: AUC60-120min of plasma glucagon during the insulin-induced hypoglycemia | Predose up to 120 mins postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The amount of exogenous glucose infused to maintain a plasma glucose level of >2.5 millimole per liter (mmol/L), after the insulin infusion is terminated. | The amount of exogenous glucose infused to maintain a plasma glucose level of >2.5 mmol/L, after the insulin infusion is terminated. | Predose up to 120 mins postdose | 
| Change from Baseline in Fasting and Post meal Glucose during Standardized Mixed-meal Tolerance Test (sMMTT) | Change from Baseline in Fasting and Post meal Glucose during sMMTT | Predose up to 120 mins postdose | 
| Change from Baseline in Glucagon Concentration at Fasting and Post meal during sMMTT | Change from Baseline in Glucagon Concentration at Fasting and Post meal during sMMTT | Predose up to 120 mins postdose |