Safety and Efficacy of Exenatide as Monotherapy and Adjunctive Therapy to Oral Antidiabetic Agents in Adolescents With Type 2 Diabetes

NCT00658021 | Completed Phase 3 Results DMC

• 2 other identifiers: D5550C00002H8O-MC-GWBQ
• Study Type: interventional
• Target: 122
• Locations: 8 countries
• Sites: 53

Brief Summary

The primary objective of this study is to test the hypothesis that glycemic control, as measured by change in hemoglobin A1c (HbA1c) from baseline to endpoint, with exenatide is superior to that of placebo after 28 weeks of treatment in adolescent patients with type 2 diabetes who are naïve to antidiabetes agents, or patients who are being treated with metformin, an SU, or a combination of metformin and an SU

Conditions

Type 2 Diabetes

Keywords

diabetes; adolescents; exenatide; Astra Zeneca

Outcome Measures

Primary Outcomes (2)

• Adjusted Change From Baseline in Glycated Hemoglobin A1c (HbA1c) at Week 28

  Change from baseline in HbA1c is reported as adjusted least square (LS) mean values at Week 28. Baseline is defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of study medication. A mixed model with repeated measures (MMRM) analysis was performed, excluding measurements after initiation of rescue medication and study drug discontinuation.

  Baseline (Day 1) and Week 28

• Number of Participants With Post-Treatment Adverse Events of Special Interest (AESI) During Safety Follow-up Period

  Post-treatment adverse events (AEs) were defined as AEs that started or worsened during the off-treatment period (Safety Follow-up Period), which was defined as the day after the Week 28/early discontinuation (ED) visit to the date of completion of the Safety Follow-up Period. The AESIs recorded were as follows: hematological malignancies, thyroid neoplasms, pancreas neoplasms, aplastic anemia, pancreatitis, pregnancy and pregnancy outcomes (including congenital anomalies).

  From 1 day after the Week 28/ED visit to 3 years after Week 28/ED visit.

Secondary Outcomes (7)

• Percentage of Participants Achieving HbA1c Goals of < 7%, <= 6.5%, and < 6.5% Through Week 28

  Weeks 0, 4, 12, 20 and 28

• Adjusted Change From Baseline in Body Weight Through Week 28

  Baseline (Day 1) up to Week 28

• Adjusted Change From Baseline in Fasting Serum Glucose (FSG) at Week 28

  Baseline (Day 1) and Week 28

• Adjusted Change From Baseline in Self-Monitored Blood Glucose (SMBG) at Week 28

  Pre-meal and 2 hours post-meal on Baseline (Day 1) and Week 28

• Adjusted Change From Baseline in Fasting Serum Insulin at Week 28

  Baseline (Day 1) and Week 28

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Subcutaneous injection, twice a day

Drug: Placebo

Exenatide 5 µg

EXPERIMENTAL

Subcutaneous injection, twice a day

Drug: Exenatide

Exenatide 10 µg

EXPERIMENTAL

Subcutaneous injection, twice a day

Drug: Exenatide

Interventions

Placebo DRUG

Subcutaneous injection, twice a day

Placebo

Exenatide DRUG

Subcutaneous injection, 5 µg, twice a day

Exenatide 5 µg

Eligibility Criteria

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

You may qualify if:

• are a male or a female between ages 10 to 17 years, inclusive. The number of patients ≥17 years of age will be limited to no more than 10% of patients in each treatment arm
• have a history of type 2 diabetes with the original diagnosis based on at least one American Diabetes Association (ADA) diagnostic criteria
• have been treated with metformin, an SU, or both metformin and an SU (with or without diet and exercise), for at least 3 months or are naïve to anti-diabetes agents and being treated with diet and exercise alone. The dose of oral agent(s) should be stable for the 30 days prior to the screening visit
• have fasting C-peptide \>0.6 ng/mL
• have HbA1c between 6.5% and 10.5%, inclusive.
• Disease Diagnostic Criteria-for the purposes of this study, patients with type 2 diabetes are defined by:
• diagnosis of type 2 diabetes, as determined by ADA diagnostic criteria and antibody testing, documented and confirmed in the patient's medical record, which includes laboratory determinations consistent with one or more of the following in the patient's medical history
• fasting blood glucose 126 mg/dL (7.0 mmol/L)
• random blood glucose 200 mg/dL (11.1 mmol/L)
• two-hour OGTT (Oral Glucose Tolerance Test) ≥ 200 mg/dL (11.1 mmol/L) AND one or more of the following: no antibodies to GAD65 OR no antibodies to islet cell antigen (ICA512).

You may not qualify if:

• have previously been exposed to exenatide or, completed or withdrawn from this study or any other study investigating exenatide
• are unwilling or unable to inject the study medication
• currently use inhaled steroids at a dose equal to or above 1000g Flovent (fluticasone propionate) daily
• have used oral steroids within the last 60 days or more than 20 days use within the past year
• have used any weight loss medication(s) within 30 days of screening
• have used insulin for more than 10 weeks during the 3 months prior to screening
• have history of renal disease, or serum creatinine \>1.6 mg/dL (141.4 µmol/L) (males) or \>1.4 mg/dL (123.8 µmol/L) (females)
• have hepatic dysfunction, defined by aspartate (AST) or alanine (ALT) transaminase \>3.0 times the upper limit of normal (ULN).

Sponsors & Collaborators

• AstraZeneca: lead
• Quintiles, Inc.: collaborator

Study Sites (53)

Research Site

Birmingham, Alabama, 35233, United States

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Tucson, Arizona, 85724, United States

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Los Angeles, California, 90048, United States

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Montclair, California, 91763, United States

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Sacramento, California, 95819, United States

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San Diego, California, 92123, United States

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Santa Ana, California, 92707, United States

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Aurora, Colorado, 80045, United States

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Melbourne, Florida, 32901, United States

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Miami, Florida, 33144, United States

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Miami Lakes, Florida, 33014, United States

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Orlando, Florida, 32806, United States

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Pensacola, Florida, 32504, United States

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Tallahassee, Florida, 32308, United States

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Dalton, Georgia, 30721, United States

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Chicago, Illinois, 60612, United States

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Chicago, Illinois, 60637, United States

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Indianapolis, Indiana, 46202, United States

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Wichita, Kansas, 67226, United States

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Dearborn, Michigan, 48124, United States

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Kansas City, Missouri, 64108, United States

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St Louis, Missouri, 63104, United States

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Reno, Nevada, 89502, United States

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Jamaica, New York, 11432, United States

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Greenville, North Carolina, 27834, United States

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Raleigh, North Carolina, 27610, United States

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Oklahoma City, Oklahoma, 73104-5008, United States

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Memphis, Tennessee, 38401, United States

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Dallas, Texas, 75235, United States

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San Antonio, Texas, 78207, United States

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Spokane, Washington, 99202, United States

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Fortaleza, 60430-370, Brazil

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Juiz de Fora, 36025-330, Brazil

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Santo André, 09030-010, Brazil

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Ahmedabad, 380006, India

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Bangalore, India

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Pune, India

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Aguascalientes, 20127, Mexico

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Culiacán, 80200, Mexico

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Guadalajara, 44650, Mexico

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Monterrey, 64710, Mexico

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San Juan del Río, 76800, Mexico

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Tamaupilas, 87070, Mexico

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Tampico, 89170, Mexico

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Quezon City, 1100, Philippines

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Moscow, 125373, Russia

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Tomsk, 634050, Russia

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Ufa, 450077, Russia

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Moloto South, 1022, South Africa

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Paarl, 7626, South Africa

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Pretoria, 0087, South Africa

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Verulam, 4345, South Africa

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Seoul, South Korea

Location

Related Links

• Clinical\_Study\_Protocol\_redacted
• Statistical Analysis Plan\_redacted

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

Exenatide

Condition Hierarchy (Ancestors)

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

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: No

Study Design

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

Study Record Dates

• First Submitted: April 8, 2008
• First Posted: April 14, 2008
• Study Start: May 30, 2008
• Primary Completion: April 18, 2019
• Study Completion: April 1, 2020
• Last Updated: December 1, 2020
• Results First Posted: December 1, 2020

Record last verified: 2020-10

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

ME (7); US (31); BR (3); RU (3); PH (1); KR (1); IN (3); ZA (4)