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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00658021
Recruitment Status : Completed
First Posted : April 14, 2008
Results First Posted : December 1, 2020
Last Update Posted : December 1, 2020
Sponsor:
Collaborator:
Quintiles, Inc.
Information provided by (Responsible Party):
AstraZeneca

Study Description
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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

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Drug: Placebo Drug: Exenatide Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 122 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Exenatide as Monotherapy and Adjunctive Therapy to Oral Antidiabetic Agents in Adolescents With Type 2 Diabetes.
Actual Study Start Date : May 30, 2008
Actual Primary Completion Date : April 18, 2019
Actual Study Completion Date : April 1, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Exenatide

Arms and Interventions
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Arm Intervention/treatment
Placebo Comparator: Placebo
Subcutaneous injection, twice a day
 Drug: Placebo
Subcutaneous injection, twice a day
Experimental: Exenatide 5 µg
Subcutaneous injection, twice a day
 Drug: Exenatide
Subcutaneous injection, 5 µg, twice a day
Experimental: Exenatide 10 µg
Subcutaneous injection, twice a day
 Drug: Exenatide
Subcutaneous injection,10 µg, twice a day


Outcome Measures
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Primary Outcome Measures :
  1. Adjusted Change From Baseline in Glycated Hemoglobin A1c (HbA1c) at Week 28 [ Time Frame: Baseline (Day 1) and 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.

  2. Number of Participants With Post-Treatment Adverse Events of Special Interest (AESI) During Safety Follow-up Period [ Time Frame: From 1 day after the Week 28/ED visit to 3 years after Week 28/ED visit. ]
    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).


Secondary Outcome Measures :
  1. Percentage of Participants Achieving HbA1c Goals of < 7%, <= 6.5%, and < 6.5% Through Week 28 [ Time Frame: Weeks 0, 4, 12, 20 and 28 ]
    The percentage of participants achieving HbA1c goals of < 7%, <= 6.5%, and < 6.5% through Week 28 were compared between treatments using the Cochran-Mantel-Haenszel (CMH) procedure, in which screening HbA1c strata and background diabetes therapy strata served as the stratification factors. The CMH analysis excluded measurements after initiation of rescue medication and study drug discontinuation with missing data treated as non-responder.

  2. Adjusted Change From Baseline in Body Weight Through Week 28 [ Time Frame: Baseline (Day 1) up to Week 28 ]
    Change from baseline in body weight is reported as adjusted LS mean values at Weeks 4, 12, 20 and 28. Baseline is defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of study medication. A MMRM analysis was performed, excluding measurements after initiation of rescue medication and study drug discontinuation.

  3. Adjusted Change From Baseline in Fasting Serum Glucose (FSG) at Week 28 [ Time Frame: Baseline (Day 1) and Week 28 ]
    Change from baseline in FSG is reported as adjusted 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. An analysis of covariance (ANCOVA) analysis was performed, excluding measurements after initiation of rescue medication and study drug discontinuation.

  4. Adjusted Change From Baseline in Self-Monitored Blood Glucose (SMBG) at Week 28 [ Time Frame: Pre-meal and 2 hours post-meal on Baseline (Day 1) and Week 28 ]
    Change from baseline in SMBG measurements are reported as adjusted LS mean values at Week 28. SMBG measurements were taken before (pre-prandial) and 2 hours after (post-prandial) the 2 main meals of the day on 3 separate days during the week before baseline (Day 1) and Week 28. Post-prandial excursions were calculated as the difference between the pre-prandial and post-prandial blood glucose concentrations (post-prandial - pre-prandial) and averaged (mean) over the 2 main meals over the 3 separate days in each period. Baseline is defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of study medication. An ANCOVA analysis was performed, excluding measurements after initiation of rescue medication and study drug discontinuation.

  5. Adjusted Change From Baseline in Fasting Serum Insulin at Week 28 [ Time Frame: Baseline (Day 1) and Week 28 ]
    Change from baseline in fasting serum insulin is reported as adjusted 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. An ANCOVA analysis was performed, excluding measurements after initiation of rescue medication and study drug discontinuation.

  6. Adjusted Change From Baseline in Homeostasis Model Assessments - Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) at Week 28 [ Time Frame: Baseline (Day 1) and Week 28 ]
    Change from baseline in HOMA-B and HOMA-S are reported as adjusted 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. An ANCOVA analysis was performed, excluding measurements after initiation of rescue medication and study drug discontinuation.

  7. Percentage of Participants Discontinuing the Study Due to Failure to Maintain Glycemic Control Through Week 28 [ Time Frame: Weeks 2, 4, 8, 12, 16, 20, 24 and 28 ]
    Participants were discontinued from the study due to failure to maintain glycemic control if either discontinuation reason on summary case report form was "Loss of glucose control" or AE with lower level Medical Dictionary for Regulatory Activities (MedDRA) term "Loss of control of blood sugar" or "Hyperglycaemia" leading to study drug discontinuation, using MedDRA Version 23.0.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   10 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria-patients are eligible to be included in the study only if they meet all of the following criteria:

  • 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).

Exclusion Criteria-patients will be excluded from the study if they meet any of the following criteria:

  • 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).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00658021


Locations
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Sponsors and Collaborators
AstraZeneca
Quintiles, Inc.
  Study Documents (Full-Text)

Documents provided by AstraZeneca:
Study Protocol  [PDF] October 13, 2017
Statistical Analysis Plan  [PDF] April 22, 2020

More Information
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Additional Information:

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00658021    
Other Study ID Numbers: D5550C00002
H8O-MC-GWBQ ( Other Identifier: company identifier )
First Posted: April 14, 2008    Key Record Dates
Results First Posted: December 1, 2020
Last Update Posted: December 1, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment.

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Supporting Materials: Study Protocol
Statistical Analysis Plan (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.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Keywords provided by AstraZeneca:
diabetes
adolescents
exenatide
Astra Zeneca
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Exenatide
 Hypoglycemic Agents
Physiological Effects of Drugs
Anti-Obesity Agents
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists