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

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)

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Placebo; Drug: Dulaglutide

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 04022-001
    • UNIFESP - Escola Paulista de Medicina
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20211-340
      • Instituto Estadual de Diabetes e Endocrinologia
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90430-001
      • Centro de Pesquisas em Diabetes
    • Porto Alegre, Rio Grande Do Sul, Brazil, 91350-200
      • Instituto da Crianca com Diabetes
  • SP
    • São Paulo, SP, Brazil, 01228-200
      • CPCLIN
    • São Paulo, SP, Brazil, 05403-000
      • Hospital da Clinicas da Faculdade de Medicina da USP
  • Sao Paulo
    • Campinas, Sao Paulo, Brazil, 13034-685
      • Hospital PUC-CAMPINAS
  • São Paulo
    • Ribeirão Preto, São Paulo, Brazil, 14051-140
      • Hospital das Clinicas da FMRP
• France
  • Le Kremlin Bicetre, France, 94275
    • Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre
  • Paris, France, 75019
    • Hopital Robert Debre
• Germany
  • Rheinland-Pfalz
    • Mayen, Rheinland-Pfalz, Germany, 56727
      • Praxis Dr. med. Landers
  • Saarland
    • Sankt Ingbert, Saarland, Germany, 66386
      • Zentrum für klinische Studien
  • Schleswig Holstein
    • Oldenburg in Holstein, Schleswig Holstein, Germany, 23758
      • RED-Institut GmbH
• Hungary
  • Budapest, Hungary, 1089
    • Heim Pál Gyermekkórház
• India
  • Delhi
    • New Delhi, Delhi, India, 110060
      • Sir Ganga Ram Hospital
  • Gujarat
    • Ahmedabad, Gujarat, India, 380007
      • Dr Jivraj Mehta Smarak Health Foundation Bakeri Medical Research Centre
  • Karmnataka
    • Bangalore, Karmnataka, India, 560017
      • Manipal Hospital
  • Karnataka
    • Bangalore, Karnataka, India, 560054
      • M S Ramaiah Medical College Hospital
  • Maharashtra
    • Pune, Maharashtra, India, 411004
      • Deenanath Mangeshkar Hospital & Research Centre
  • Punjab
    • Chandigarh, Punjab, India, 160012
      • Post Graduate Institute of Medical Education & Research
  • Uttar Pradesh
    • Varanasi, Uttar Pradesh, India, 221005
      • Banaras Hindu University - BHU
  • West Bengal
    • Kolkata, West Bengal, India, 700054
      • Apollo Gleneagles Hospitals Kolkata
    • Kolkata, West Bengal, India, 700017
      • Park Clinic
• Mexico
  • Puebla, Mexico, 72190
    • Hospital Angeles Puebla
  • Veracruz, Mexico, 91910
    • ARKE Estudios Clínicos S.A. de C.V.
  • Federal District
    • Mexico City, Federal District, Mexico, 03810
      • Health Pharma Professional Research, S.A. de C.V.
  • Jalisco
    • Zapopan, Jalisco, Mexico, 45116
      • Centro de Inv. Medica de Occidente, SC
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64710
      • Centro Medico San Francisco
  • Tamaulipas
    • Tampico, Tamaulipas, Mexico, 89249
      • Cli-nica Hospital Cemain
• Puerto Rico
  • Bayamon, Puerto Rico, 00959
    • Centro de Diabetes y Endocrinologia Pediatrica de PR
• Saudi Arabia
  • Riyadh, Saudi Arabia, 11472
    • King Saud University Hospital
  • Riyadh, Saudi Arabia, 12769
    • King Salman bin Abdulaziz Hospital - Diabetic Center
• Turkey
  • Ankara, Turkey, 06080
    • Sami Ulus Education & Research Hospital
  • Duzce, Turkey, 81620
    • Duzce University Medical Faculty
  • Samsun, Turkey, 55139
    • Ondokuz Mayis University Medical Faculty
  • Mamak
    • Ankara, Mamak, Turkey, 06100
      • Ankara University Medicine Hospital
• United Kingdom
  • Lancashire
    • Liverpool, Lancashire, United Kingdom, L14 5AB
      • Alder Hey Children's Hospital
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS9 7TF
      • St James's University Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama Birmingham
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • California
    • Anaheim, California, United States, 92805
      • Advanced Research Center
    • Los Angeles, California, United States, 90027
      • Division of Endocrinology, Diabetes, and Metabolism
    • Orange, California, United States, 92868
      • Childrens Hospital of Orange County
    • Sacramento, California, United States, 95821
      • Center of Excellence in Diabetes & Endocrinology
    • San Diego, California, United States, 92123
      • Rady Childrens Hospital - San Diego
    • San Jose, California, United States, 95148
      • JC Cabaccan
    • Vallejo, California, United States, 94592
      • Touro University
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Orlando, Florida, United States, 32803
      • Florida Center for Endocrinology & Metabolism
  • Idaho
    • Boise, Idaho, United States, 83712
      • St. Luke's Regional Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Hospital
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808-4124
      • Pennington Biomedical Research Center
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • ECU Pediatric Specialty Care
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Childrens Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Childrens Hospital of Pittsburgh
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital Research Foundation
    • Tacoma, Washington, United States, 98405
      • Multicare Health System
  • West Virginia
    • Charleston, West Virginia, United States, 25302
      • CAMC Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Placebo/0.75 milligram (mg) Dulaglutide; 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: Placebo; Administered SC; Drug: Dulaglutide; Administered SC; Other Names: LY2189265
EXPERIMENTAL: 0.75 mg Dulaglutide; 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; Administered SC; Other Names: LY2189265
EXPERIMENTAL: 1.5 mg Dulaglutide; 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; Administered SC; 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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Arslanian SA, Hannon T, Zeitler P, Chao LC, Boucher-Berry C, Barrientos-Perez M, Bismuth E, Dib S, Cho JI, Cox D; AWARD-PEDS Investigators. Once-Weekly Dulaglutide for the Treatment of Youths with Type 2 Diabetes. N Engl J Med. 2022 Aug 4;387(5):433-443. doi: 10.1056/NEJMoa2204601. Epub 2022 Jun 4.

Helpful Links

• A Study of Dulaglutide (LY2189265) in Children and Adolescents With Type 2 Diabetes (AWARD-PEDS)

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 29, 2016
• Primary Completion (ACTUAL): June 12, 2021
• Study Completion (ACTUAL): January 12, 2022

Study Registration Dates

• First Submitted: November 10, 2016
• First Submitted That Met QC Criteria: November 10, 2016
• First Posted (ESTIMATE): November 15, 2016

Study Record Updates

• Last Update Posted (ACTUAL): July 1, 2022
• Last Update Submitted That Met QC Criteria: June 7, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Pediatrics
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Dulaglutide
• Other Study ID Numbers: 14171; H9X-MC-GBGC (OTHER: Eli Lilly and Company); 2016-000361-22 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR