A Study to Evaluate Tirzepatide (LY3298176) in Pediatric and Adolescent Participants With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin or Basal Insulin or Both

Study Overview
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Brief Summary
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The purpose of this study is to learn more about the safety and efficacy of tirzepatide compared to placebo in children or teenagers with type 2 diabetes taking metformin, or basal insulin, or both. The overall study will last about 60 weeks with up to 14 clinic visits and 6 phone visits. Clinic visits will include blood sample collection, physical exam and questionnaire.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study With an Open-Label Extension Assessing the Efficacy, Safety, and Pharmacokinetics/Pharmacodynamics of Tirzepatide in Pediatric and Adolescent Participants With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin, or Basal Insulin, or Both

Conditions
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T2D, Type2 Diabetes, Diabetes Mellitus, Diabetes Mellitus, Type 2, T2DM (Type 2 Diabetes Mellitus), Glucose Metabolism Disorders, Endocrine System Diseases, Metabolic Disease

Intervention / Treatment
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* Drug: Tirzepatide Dose 1
* Drug: Tirzepatide Dose 2
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged 10 to below 18 years at screening visit Have type 2 diabetes, treated with diet and exercise and metformin and/or basal insulin. Metformin and/or basal insulin dose must be stable for at least 90 days prior to study screening. Have HbA1c >6.5% to ≤11% at screening Have body weight ≥50 kilogram (kg) 110 pounds and BMI of >85th percentile of the general age and gender-matched population for that country or region. Exclusion Criteria: Have Type 1 diabetes mellitus (T1DM), or positive GAD65 or IA2 antibodies After the T2DM diagnosis, have a history of diabetic ketoacidosis or hyperosmolar syndrome Have had ≥1 episode of severe hypoglycemia and/or ≥1 episode of hypoglycemic unawareness within the last 6 months. Have family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2). Had chronic or acute pancreatitis any time prior to study entry Female participants who are pregnant or breast feeding or intending to become pregnant. Using prescription or over the counter medications for weight loss within 90 days of the screening visit.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tirzepatide Dose 1<br>Double-Blind: Participants receive Tirzepatide by weekly subcutaneous (SC) injection starting with a low dose then increase to a higher dose every four weeks until maintenance dose level 1 is reached. Open-Label: Participants will continue to receive Tirzepatide at the last dose level | Drug: Tirzepatide Dose 1<br>* Administered SC<br>|
| Experimental: Tirzepatide Dose 2<br>Double-Blind: Participants receive Tirzepatide by weekly SC injection starting with a low dose then increase to a higher dose every four weeks until maintenance dose level 2 is reached. Open-Label: Participants will continue to receive Tirzepatide at the last dose level | Drug: Tirzepatide Dose 2<br>* Administered SC<br>|
| Placebo Comparator: Placebo<br>Double-Blind: Participants receive placebo during the 30-week double-blind period. Open-Label: Participants will switch to Tirzepatide by weekly SC injection starting with a low dose then increase to a higher dose every four weeks until maintenance dose level 1 is reached. | Drug: Tirzepatide Dose 1<br>* Administered SC<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 |
| --- | --- | --- |
| Change From Baseline in Hemoglobin A1c (HbA1c) |  | Baseline, Week 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in HbA1c (Individual Doses) |  | Baseline, Week 30 | 
| Change From Baseline in Body Mass Index (BMI) Standard Deviation Score (age and sex-matched) |  | Baseline, Week 30 | 
| Change From Baseline in Fasting Serum Glucose (FSG) |  | Baseline, Week 30 | 
| Percentage of Participants Who Achieve ≤6.5% of HbA1c |  | Week 30 | 
| Percentage of Participants Who Achieve <7.0% of HbA1c |  | Week 30 | 
| Percentage of Participants Who Achieve <5.7% of HbA1c |  | Week 30 | 
| Change From Baseline for Serum Lipid Levels |  | Baseline, Week 30 | 
| Change From Baseline in Height Standard Deviation Score (SDS) |  | Baseline, Week 30 | 
| Change From Baseline in Weight SDS |  | Baseline, Week 30 | 
| Pharmacokinetics (PK): Area Under the Concentration Curve (AUC), Steady State (ss) of Tirzepatide |  | Baseline to Week 30 | 
| Change From Baseline in PedsQL Generic Core Scale | The PedsQL Generic Core Scale has 23 items that measure the core dimensions of health: physical, emotional, and social and school functioning. Scores range from 0 to 100. Higher scores indicate better health related quality of life. | Baseline, Week 52 | 
| Change From Baseline PedsQL (3.2) Diabetic Module | The PedsQL 3.2 Diabetes Module has 33 items for ages 13 to 45 years, and 32 items (1 less item for the Worry Scale) for ages 2 to 12 years. The 5 dimensions consist of diabetes symptoms, treatment barriers, treatment adherence, worry and communication. Scores range from 0 to 100. Higher scores indicate less problems. | Baseline, Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GLP-1 RA, Glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), GIP/GLP-1 dual receptor agonist, Incretins