A Study of Dulaglutide (LY2189265) in Children and Adolescents With Type 2 Diabetes

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics and pharmacodynamics of the study drug dulaglutide compared to placebo in pediatric participants with type 2 diabetes. The study duration is approximately 60 weeks.

Official Title
-----------------
A Randomized, Double-Blind Study With an Open-Label Extension Comparing the Effect of Once-Weekly Dulaglutide With Placebo in Pediatric Patients With Type 2 Diabetes Mellitus (AWARD-PEDS: Assessment of Weekly AdministRation of LY2189265 in Diabetes-PEDiatric Study)

Conditions
-----------------
Type 2 Diabetes

Intervention / Treatment
-----------------
* Drug: Dulaglutide
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have type 2 diabetes, treated with diet and exercise, with or without metformin and/or basal insulin. Metformin and/or basal insulin dose must be stable for at least 8 weeks prior to study screening. Have HbA1c >6.5% to ≤11% at screening visit. If newly diagnosed and not on medicine for diabetes, HbA1c must be between >6.5 % to ≤9%. Have a BMI (body mass index) >85 percentile for age, gender and body weight ≥50 kilograms (110 pounds). Exclusion Criteria: Known type 1 diabetes, or positive GAD65 or IA2 antibodies, or history of diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome. A history of, or at risk for pancreatitis. Self or family history of Multiple Endocrine Neoplasia (MEN) type 2A or B, thyroid C-cell hyperplasia or medullary thyroid cancer, or a blood calcitonin result ≥20 picograms per milliliter (pg/ml) at screening. A systolic blood pressure of ≥160 millimeters of mercury (mmHg) or diastolic ≥100 mmHg. Active or treated cancer. A blood disorder where an accurate HbA1c may not be obtainable. A female of childbearing age, sexually active and not on birth control. Pregnant or plan to be pregnant during the study, or breastfeeding. Taking any diabetic medication other than metformin or basal insulin and have not stopped it 3 months prior to the screening visit (6 weeks for bolus or mealtime insulin). Have taken oral steroids within the last 60 days or more than 20 days use within the past year or 1000 micrograms fluticasone propionate per day. Using prescription weight loss medications in the last 30 days, or plan to use. Taking psychiatric medications for depression or illness or attention deficit hyperactivity disorder (ADHD) if, the doses has changed within the last 3 months.

Ages Eligible for Study
-----------------
Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo/0.75 milligram (mg) Dulaglutide<br>Participants received placebo administered subcutaneously (SC) for 26 weeks during the double-blind period and open-label 0.75 mg/week dulaglutide for 26 weeks during the Open Label Extension (OLE). | Drug: Dulaglutide<br>* Administered SC<br>* Other names: LY2189265;Drug: Placebo<br>* Administered SC<br>|
| Experimental: 0.75 mg Dulaglutide<br>Participants received 0.75 mg/week dulaglutide administered SC for 26 weeks during the double-blind period and open-label 0.75 mg/week for 26 weeks during the OLE. | Drug: Dulaglutide<br>* Administered SC<br>* Other names: LY2189265;|
| Experimental: 1.5 mg Dulaglutide<br>Participants received 1.5 mg/week dulaglutide administered SC for 26 weeks during the double-blind period and open-label 1.5 mg/week for 26 weeks during the OLE. | Drug: Dulaglutide<br>* Administered SC<br>* Other names: LY2189265;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hemoglobin A1c (HbA1c) (Pooled Doses) at Week 26 | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least square (LS) mean in HbA1c was calculated using a restricted maximum likelihood (REML) based mixed-effects model for repeated measures (MMRM) and adjusted by, baseline + insulin Use + metformin Use + treatment + time + treatment*time (Type III sum of squares). Variance-covariance structure = unstructured (for actual value) / unstructured (for change from baseline). | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c (Individual Doses) at Week 26 | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean in HbA1c was calculated using a REML based MMRM and adjusted by, baseline + insulin use + metformin use + treatment + time + treatment*time (Type III sum of squares). Variance-covariance structure = unstructured (for actual value) / unstructured (for change from baseline). | Baseline, Week 26 | 
| Change From Baseline in Fasting Blood Glucose (FBG) at Week 26 | Fasting blood glucose is a test to determine how much glucose (sugar) is in a blood sample after an overnight fast. Least squares (LS) means were calculated using a mixed-effects model for repeated measures (MMRM) analysis and adjusted by baseline, strata, treatment, time, treatment*time, (Type III sum of squares). Variance-Covariance structure = Unstructured (for actual value) / Unstructured (for change from baseline). Strata refer to: insulin use + metformin use + baseline HbA1c group [ less than (<) 8%, greater than or equal to (>=) 8%). | Baseline, Week 26 | 
| Percentage of Participants With HbA1c ≤7.0% | The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100. | Week 26 | 
| Change From Baseline in Body Mass Index (BMI) at Week 26 | BMI is an estimate of body fat based on body weight divided by height squared. LS mean were calculated using a MMRM analysis and adjusted by baseline, strata, treatment, time, treatment*time, (Type III sum of squares). Variance-Covariance structure = Unstructured (for actual value) / Unstructured (for change from baseline). Strata refer to: insulin use + metformin use + baseline HbA1c group (< 8%, >= 8%). | Baseline, Week 26 | 
| Percentage of Participants With Self-Reported Events of Hypoglycemia | Summary and analysis of Incidence of all hypoglycemia with Plasma Glucose <54mg/dL. | Week 26 | 
| Percentage of Participants Requiring Rescue for Severe, Persistent Hyperglycemia | Percentage of Participants Requiring Rescue for Severe, Persistent Hyperglycemia was summarized. | Week 26 | 
| Number of Participants With Adjudicated Pancreatitis | The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. | Week 26 | 
| Change From Baseline in Pancreatic Enzymes at Week 26 | Serum Amylase (total and pancreas-derived) and lipase concentrations were measured. | Baseline, Week 26 | 
| Number of Participants With Thyroid Treatment-Emergent Adverse Events | Number of Participants with Thyroid Treatment-Emergent Adverse Events were summarized. | Week 26 | 
| Change From Baseline in Serum Calcitonin at Week 26 | Change from Baseline in Serum Calcitonin was evaluated. | Baseline, Week 26 | 
| Percentage of Participants With Allergic, Hypersensitivity Reactions | The percentage of Participants with Allergic and hypersensitivity reactions that were considered possibly related to study drug by the investigator are presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. | Week 26 | 
| Percentage of Participants With Injection Site Reactions | The percentage of participants with at least one treatment-emergent injection site reaction is presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. | Week 26 | 
| Number of Participants With Anti-Dulaglutide Antibodies | Dulaglutide anti-drug antibodies (ADA) were assessed at baseline, Weeks 26 and 56. A participant was considered to have treatment-emergent (TE) dulaglutide ADAs if the participant had at least 1 titer that was TE relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement. | Baseline through Week 56 | 
| Pharmacokinetics (PK): Maximum Concentration of Dulaglutide at Steady-state (Cmax,ss) | PK: Maximum Concentration of Dulaglutide at steady-state (Cmax,ss) was derived by a population pharmacokinetics approach. As part of addendum, additional PK samples were taken at week 9. | Week 9: pre-dose,1 to 12 hours post dose and 24 to 96 hours post dose; Week 13: predose and 1 to 12 hours post dose; Week 26: predose; Week 39: up to 2 days postdose; Week 52 and Week 56: PK sample can be taken at any time during the visit | 
| PK: Area Under the Concentration Time Curve Over a 1-week Interval of Dulaglutide at Steady-State [AUC(0-168)ss] | PK: Area Under the Concentration Time Curve over a 1-week interval of Dulaglutide at Steady-State [AUC(0-168)ss] was derived by a population pharmacokinetics approach. As part of addendum, additional PK samples were taken at week 9. | Week 9: pre-dose,1 to 12 hours post dose and 24 to 96 hours post dose; Week 13: predose and 1 to 12 hours post dose; Week 26: predose; Week 39: up to 2 days postdose; Week 52 and Week 56: PK sample can be taken at any time during the visit | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pediatrics