A Phase 2 Study of LY3209590 in Participants With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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The reason for this study is to see if the study drug LY3209590 is safe and effective in participants with type 2 diabetes.

Official Title
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A Phase 2, Parallel, Comparator-Controlled Trial to Evaluate the Safety and Efficacy of LY3209590 in Insulin-Naïve Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: LY3209590
* Drug: Insulin Degludec


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have type 2 diabetes mellitus according to the World Health Organization (WHO) criteria treated with a stable dose of metformin in combination with a stable dose of Dipeptidyl Peptidase IV (DPPIV) inhibitor and/or a Sodium-glucose co-transporter-2 (SGLT2) inhibitor for at least 3 months prior to screening Participants must have a HbA1c value of 7.0% to 9.5%, inclusive Participants must have a body mass index (BMI) between 20 and 45 kilograms per meter squared (kg/m²), inclusive Exclusion Criteria: Have type 1 diabetes mellitus or latent autoimmune diabetes Have any episodes of severe hypoglycemia and/or hypoglycemia unawareness within the 6 months prior to screening Have any of the following cardiovascular (CV) conditions: acute myocardial infarction, New York Heart Association Class III or IV heart failure, or cerebrovascular accident (stroke) Have acute or chronic hepatitis, or obvious clinical signs or symptoms of any other liver disease Have an estimated glomerular filtration rate (eGFR) <30 milliliters/minute/1.73 m² Have active or untreated cancer Are receiving chronic (>14 days) systemic glucocorticoid therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3209590 Algorithm 1 (Paper)<br>Algorithm 1 is a paper-based algorithm where dose adjustments were manually determined by the investigator based on fasting glucose and hypoglycemia data. LY3209590 was provided in a 20 milligram (mg) vial of reconstitutable lyophilized powder. Participants received individualized LY3209590 loading dose based on the baseline median fasting glucose and body weight by subcutaneous (SC) injection on day 1 followed by weekly adjustments for the first 12 weeks, then every 4 weeks, of a 26-week treatment period, to achieve target fasting glucose of <=100 milligrams per deciliter (mg/dL). | Drug: LY3209590<br>* Administered SC<br>|
| Experimental: LY3209590 Algorithm 2 (Digital)<br>Algorithm 2 is a computer-based algorithm to determine dose adjustments. LY3209590 was provided in a 20 mg vial of reconstitutable lyophilized powder. Participants received individualized LY3209590 loading dose based on the baseline median fasting glucose and body weight by SC injection on day 1 followed by weekly adjustments for the first 12 weeks, then every 4 weeks, of a 26-week treatment period, to achieve target fasting glucose of <=100 mg/dL. As per protocol amendment (d) approved on 28-Oct-2020, this arm was terminated during the early enrollment phase due to technical issues with data entry. | Drug: LY3209590<br>* Administered SC<br>|
| Active Comparator: Insulin Degludec<br>Insulin degludec was provided as 100 units/milliliter (U/mL) in a prefilled pen. Participants received individually adjusted doses once daily by SC injection with a starting dose of 10 units, during the 26-week treatment period, to achieve target fasting blood glucose of <=100 mg/dL. | Drug: Insulin Degludec<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hemoglobin A1c (HbA1c) | HbA1c is the glycosylated fraction of haemoglobin A. It is measured to identify average blood glucose concentration over prolonged periods of time. Least squares (LS) mean change from baseline was analysed by mixed model repeated measures (MMRM) model with treatment, country, Dipeptidyl peptidase IV (DPPIV) (yes/no), Sodium-glucose Cotransporter-2 (SGLT2) (yes/no), baseline body mass index (BMI) [<30, >=30]), visit, and treatment by visit interaction as fixed effects and the baseline HbA1c as a covariate. | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Serum Glucose | LS mean change from baseline was analysed by MMRM model with treatment, country, DPPIV (yes/no), SGLT2 (yes/no), baseline BMI [<30, >=30]), visit, and treatment by visit interaction as fixed effects and the baseline fasting serum glucose as a covariate. | Baseline, Week 26 | 
| Rate of Documented Hypoglycemia | Documented hypoglycemia is defined as any time a participant reports a self-monitoring blood glucose <54 mg/dL (3.0 millimole per liter (mmol/L)). Rate of documented hypoglycemia per year during defined period is calculated by the number of documented hypoglycemia events within the period divided by the number of days participant at risk within the period*365.25 days. | Baseline through Week 26 | 
| Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3209590 | AUC of LY3209590 was calculated for individual participants using the participants' Week 26 LY3209590 dose amount and estimated clearance value. | Week 26 |