Safety and Efficacy Study of Exenatide Once Weekly in Adolescents With Type 2 Diabetes

NCT01554618 | Completed Phase 3 Results DMC

• 1 other identifier: D5551C00002
• Study Type: interventional
• Target: 84
• Locations: 7 countries
• Sites: 35

Brief Summary

The study examines the Safety and efficacy study of exenatide once weekly in children and adolescents with type 2 diabetes

Conditions

Children and Adolescent With Type 2 Diabetes

Keywords

exenatide; type 2 diabetes; GLP-1 receptor agonist

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) to Week 24 (Controlled Assessment Period)

  Change from baseline in HbA1c (%) to Week 24 during the controlled assessment period is reported as adjusted least square (LS) mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A mixed model with repeated measures (MMRM) analysis was performed, excluding data collected after initiation of rescue medication or premature discontinuation of study medication.

  Baseline (Week 0) and Week 24

• Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period)

  A controlled assessment period AE was defined as an AE starting on or after day of first dose of study medication up to but not including Week 24 for patients entering the extension period. For patients not entering the extension period, the period was defined up to and including last dose of study medication + 7 days (+ 90 days for serious AEs \[SAEs\] and other clinically significant or related AEs). The Investigator assessed AEs for causal relationship to study drug medication.

  Day 1 (Week 0) up to Week 24, plus up to a maximum of 90 days follow up

• Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24

  Percentage of patients positive for ADAs up to Week 24 for the exenatide treatment group is reported. Baseline was the antibody measurement at Week 0 (Day 1). A negative or missing antibody measurement was considered negative at baseline. High positive = antibody titers ≥ 625, including baseline assessment. Low positive = antibody titers \< 625, including baseline assessment. A patient was said to have treatment-emergent ADA positive at a visit if the antibody test was positive after the first dose of exenatide following a negative or missing antibody measurement, or the titer increased by at least 1 titration category from a detectable measurement prior to first dose of randomized study medication.

  Samples were collected on Day 1 (Week 0), Week 4, Week 8, Week 12 and Week 24

Secondary Outcomes (20)

• Change From Baseline in Fasting Plasma Glucose (FPG) Concentration to Week 24 (Controlled Assessment Period)

  Baseline (Week 0) and Week 24

• Change From Baseline in Body Weight to Week 24 (Controlled Assessment Period)

  Baseline (Week 0) and Week 24

• Change From Baseline in Fasting Insulin to Week 24 (Controlled Assessment Period)

  Baseline (Week 0) and Week 24

• Percentage of Patients Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 (Controlled Assessment Period)

  At Week 24

• Change From Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period)

  Baseline (Week 0) and Week 24

Study Arms (2)

EQW

EXPERIMENTAL

Exenatide once weekly

Drug: Exenatide Once Weekly

Placebo

PLACEBO COMPARATOR

Placebo once weekly

Drug: Placebo

Interventions

Exenatide Once Weekly DRUG

2 mg exenatide once weekly

Also known as: BYDUREON

EQW

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 10 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

Each patient must meet the following criteria to be enrolled in this study. 1. Is a child or an adolescent of 10 to \<18 years old, at Visit 1 (Screening) 2. Has been diagnosed with type 2 diabetes mellitus per American Diabetes Association diagnostic criteria 3. HbA1c of 6.5% to 11.0%, inclusive, in patients not taking insulin/SU, and of 6.5% to 12.0%, inclusive, in patients taking insulin/SU, at Visit 1 (Screening) 4. Has a C-peptide of \>0.6 ng/L at Visit 1 (Screening) 5. Has been treated with diet and exercise alone or in combination with a stable dose of an oral antidiabetic agent (e.g., metformin and/or SU) and/or insulin for their type 2 diabetes for at least 2 months prior to Visit 1 (Screening) 6. Has a fasting plasma glucose concentration \<280 mg/dL (15.5 mmol/L) at Visit 1 (Screening) Patients who meet any of the following criteria will be excluded from the study. 1. Has a clinically significant medical condition that could potentially affect study participation and/or personal well-being, as judged by the Investigator, including but not limited to the following conditions: 1. Hepatic disease (defined by aspartate or alanine transaminase \>3.0 times the upper limit of normal (ULN) 2. Renal disease or serum creatinine \>1.5 mg/dL (132.6 µmol/L) (males) or 1.4 mg/dL (123.8 µmol/L) (females) 3. Gastrointestinal disease deemed significant by the Investigator 4. Organ transplantation 5. Chronic infection (e.g., tuberculosis, human immunodeficiency virus, hepatitis B virus, or hepatitis C virus) 6. Clinically significant malignant disease (with the exception of basal and squamous cell carcinoma of the skin) within 5 years of Visit 1 (Screening) 2. Has positive antibody titers to glutamic acid decarboxylase (GAD65) or islet cell antigen (ICA512) at Visit 1 (Screening) 3. Has a personal or family history of elevated calcitonin, calcitonin \>100 ng/L, medullary thyroid carcinoma, or multiple endocrine neoplasia-2 4. Has ever used exenatide (exenatide once weekly \[exenatide LAR\], exenatide BID, BYETTA, or any other formulation) or any glucagon-like peptide-1 (GLP-1) receptor agonist (e.g., liraglutide \[Victoza®\]) 5. Is pregnant

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (35)

Research Site

Los Angeles, California, 90078, United States

Location

Research Site

New Haven, Connecticut, 06511, United States

Location

Research Site

Iowa City, Iowa, 52242, United States

Location

Research Site

Kansas City, Kansas, 64111, United States

Location

Research Site

Louisville, Kentucky, 40202, United States

Location

Research Site

Boston, Massachusetts, 02115, United States

Location

Research Site

Jackson, Mississippi, 39216-4505, United States

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Research Site

Buffalo, New York, 14222, United States

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Chapel Hill, North Carolina, 27599, United States

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Research Site

Charlotte, North Carolina, 28205, United States

Location

Research Site

Cleveland, Ohio, 44106, United States

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Research Site

Oklahoma City, Oklahoma, 73104, United States

Location

Research Site

Rapid City, South Dakota, 57701, United States

Location

Research Site

Nashville, Tennessee, 37232, United States

Location

Research Site

Dallas, Texas, 75390, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Research Site

Pleven, 5800, Bulgaria

Location

Research Site

Sevlievo, 5400, Bulgaria

Location

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Baja, 6500, Hungary

Location

Research Site

Budapest, 1023, Hungary

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Budapest, 1083, Hungary

Location

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Budapest, 1094, Hungary

Location

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Szeged, 6725, Hungary

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Beersheba, 84101, Israel

Location

Research Site

Haifa, 31096, Israel

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Ramat Gan, 5265601, Israel

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Kuwait City, 1180, Kuwait

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Research Site

Aguascalientes, 20016, Mexico

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Research Site

Durango, 34000, Mexico

Location

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Guadalajara, 44130, Mexico

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Veracruz, 91910, Mexico

Location

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Chernivts?, 58001, Ukraine

Location

Research Site

Ivano-Frankivsk, 76014, Ukraine

Location

Research Site

Kharkiv Region, 61002, Ukraine

Location

Research Site

Odesa, 65031, Ukraine

Location

Related Publications (1)

• Tamborlane WV, Bishai R, Geller D, Shehadeh N, Al-Abdulrazzaq D, Vazquez EM, Karoly E, Troja T, Doehring O, Carter D, Monyak J, Sjostrom CD. Once-Weekly Exenatide in Youth With Type 2 Diabetes. Diabetes Care. 2022 Aug 1;45(8):1833-1840. doi: 10.2337/dc21-2275.

  PMID: 35679098 DERIVED

Related Links

• redacted SAP
• redacted CSP
• CSR Synopsis

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Exenatide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Limitations and Caveats

For statistical analyses of change from baseline in HOMA-B and HOMA-S, due to the limited sample size (n=14 and n=7 in the extenatide and placebo groups, respectively) it is difficult to accurately interpret these data. The study design included an extended safety follow-up period which continued for up to 3 years or until the increase in height between two 6-month interval visits was \<5 mm (whichever came first). No study medication was administered during the extended safety follow-up period.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2012
• First Posted: March 15, 2012
• Study Start: December 2, 2011
• Primary Completion: May 6, 2020
• Study Completion: May 5, 2021
• Last Updated: November 30, 2021
• Results First Posted: December 3, 2020

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (16); IL (3); BU (2); HU (5); KU (1); ME (4); UA (4)