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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 Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Type 2 Diabetes
Interventions Drug: Placebo
Drug: Exenatide
Enrollment 122
Recruitment Details This study was conducted in adolescents (aged 10 to 17 years inclusive) with type 2 diabetes who were naïve to antidiabetics, or were receiving metformin, an sulfonylurea (SU) or a combination of metformin and an SU in 7 countries (Brazil, India, South Korea, Mexico, Russia, the United States and South Africa) between 30 May 2008 and 01 April 2020.
Pre-assignment Details The study commenced with a 1-week, single-blind, injectable placebo lead-in period before participants were randomized to 1 of 3 treatment groups: exenatide 5 microgram (mcg) twice daily, exenatide 10 mcg twice daily, or placebo twice daily. A total of 122 participants were randomized in this study.
Arm/Group Title Exenatide 5 mcg Exenatide 10 mcg Placebo
Hide Arm/Group Description Adolescent participants received exenatide 5 mcg subcutaneous (SC) injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 millimeter (mm) between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period. Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period. Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
Period Title: 28-Week Treatment Period
Started [1] 42 38 42
Received Treatment 40 38 42
Completed [2] 31 25 25
Not Completed 11 13 17
Reason Not Completed
Adverse Event             3             1             0
Developed study withdrawal criteria             0             2             0
Protocol Violation             0             2             1
Withdrawal by Subject             1             1             3
Physician Decision             1             2             1
Withdrawal by parent/guardian             1             1             1
Loss of glucose control             1             1             10
Other             2             3             1
Did not receive treatment             2             0             0
[1]
Randomized to treatment.
[2]
Completed the Week 28 treatment period.
Period Title: Long-term Safety Follow-up Period
Started [1] 7 [1] 5 [1] 7 [1]
Completed [2] 7 2 7
Not Completed 0 3 0
Reason Not Completed
Withdrawal by Subject             0             1             0
Physician Decision             0             2             0
[1]
Entered safety follow-up period.
[2]
Completed safety follow-up period.
Arm/Group Title Exenatide 5 mcg Exenatide 10 mcg Placebo Total
Hide Arm/Group Description Adolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period. Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period. Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period. Total of all reporting groups
Overall Number of Baseline Participants 42 38 42 122
Hide Baseline Analysis Population Description
The Intent-To-Treat analysis set included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 42 participants 38 participants 42 participants 122 participants
13.7  (1.94) 14.0  (1.95) 14.4  (1.82) 14.0  (1.91)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 42 participants 38 participants 42 participants 122 participants
Female
31
  73.8%
22
  57.9%
29
  69.0%
82
  67.2%
Male
11
  26.2%
16
  42.1%
13
  31.0%
40
  32.8%
Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 42 participants 38 participants 42 participants 122 participants
White
7
  16.7%
5
  13.2%
13
  31.0%
25
  20.5%
Black or African American
14
  33.3%
8
  21.1%
7
  16.7%
29
  23.8%
Asian
3
   7.1%
2
   5.3%
5
  11.9%
10
   8.2%
American Indian or Alaska Native
0
   0.0%
1
   2.6%
0
   0.0%
1
   0.8%
Hispanic
18
  42.9%
22
  57.9%
17
  40.5%
57
  46.7%
[1]
Measure Description: Ethnicity not collected and Hispanic was collected as a Race in this study.
1.Primary Outcome
Title Adjusted Change From Baseline in Glycated Hemoglobin A1c (HbA1c) at Week 28
Hide Description 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.
Time Frame Baseline (Day 1) and Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
The Evaluable Analysis Set included all randomized participants who received at least 1 dose of randomized study medication and had a baseline and at least 1 post-baseline HbA1c assessment. For analysis of efficacy, a decision was made with agreement by the European Medicines Agency and the Food and Drug Administration to pool participants from both exenatide groups (Total EBID) and compare this pooled group with placebo.
Arm/Group Title Total Exenatide Twice Daily (EBID) Placebo
Hide Arm/Group Description:

Efficacy data from participants from both exenatide groups (Total EBID) was pooled for comparison with placebo.

Adolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks; or Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks.

Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
Overall Number of Participants Analyzed 78 42
Least Squares Mean (Standard Error)
Unit of Measure: percentage (%HbA1c)
0.11  (0.215) 0.38  (0.293)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Total Exenatide Twice Daily (EBID), Placebo
Comments Adjusted LS mean and treatment group difference in the change from baseline values at visit are obtained from a MMRM including treatment, baseline HbA1c, background diabetes therapy strata, week of visit, baseline HbA1c-by-visit interaction and treatment-by-visit interaction as fixed effects using an unstructured covariance matrix.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.444
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-1.01 to 0.45
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.363
Estimation Comments [Not Specified]
2.Primary Outcome
Title Number of Participants With Post-Treatment Adverse Events of Special Interest (AESI) During Safety Follow-up Period
Hide Description 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).
Time Frame From 1 day after the Week 28/ED visit to 3 years after Week 28/ED visit.
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Follow-up Analysis Set included all participants who had at least 1 safety follow-up period assessment visit.
Arm/Group Title Exenatide 5 mcg Exenatide 10 mcg Placebo
Hide Arm/Group Description:
Adolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
Overall Number of Participants Analyzed 7 5 7
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
3.Secondary Outcome
Title Percentage of Participants Achieving HbA1c Goals of < 7%, <= 6.5%, and < 6.5% Through Week 28
Hide Description 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.
Time Frame Weeks 0, 4, 12, 20 and 28
Hide Outcome Measure Data
Hide Analysis Population Description
The Evaluable Analysis Set included all randomized participants who received at least 1 dose of randomized study medication and had a baseline and at least 1 post-baseline HbA1c assessment. For analysis of efficacy, a decision was made with agreement by the European Medicines Agency and the Food and Drug Administration to pool participants from both exenatide groups (Total EBID) and compare this pooled group with placebo.
Arm/Group Title Total Exenatide Twice Daily (EBID) Placebo
Hide Arm/Group Description:

Efficacy data from participants from both exenatide groups (Total EBID) was pooled for comparison with placebo.

Adolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks; or Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks.

Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
Overall Number of Participants Analyzed 78 42
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
HbA1c < 7%: Week 0
37.2
(26.5 to 47.9)
38.1
(23.4 to 52.8)
HbA1c < 7%: Week 4
44.9
(33.8 to 55.9)
42.9
(27.9 to 57.8)
HbA1c < 7%: Week 12
43.6
(32.6 to 54.6)
33.3
(19.1 to 47.6)
HbA1c < 7%: Week 20
35.9
(25.3 to 46.5)
35.7
(21.2 to 50.2)
HbA1c < 7%: Week 28
33.3
(22.9 to 43.8)
28.6
(14.9 to 42.2)
HbA1c <=6.5%: Week 0
17.9
(9.4 to 26.5)
16.7
(5.4 to 27.9)
HbA1c <=6.5%: Week 4
29.5
(19.4 to 39.6)
23.8
(10.9 to 36.7)
HbA1c <=6.5%: Week 12
33.3
(22.9 to 43.8)
23.8
(10.9 to 36.7)
HbA1c <=6.5%: Week 20
24.4
(14.8 to 33.9)
19.0
(7.2 to 30.9)
HbA1c <=6.5%: Week 28
23.1
(13.7 to 32.4)
19.0
(7.2 to 30.9)
HbA1c <6.5%: Week 0
15.4
(7.4 to 23.4)
7.1
(0.0 to 14.9)
HbA1c <6.5%: Week 4
26.9
(17.1 to 36.8)
21.4
(9.0 to 33.8)
HbA1c <6.5%: Week 12
30.8
(20.5 to 41.0)
19.0
(7.2 to 30.9)
HbA1c <6.5%: Week 20
21.8
(12.6 to 31.0)
19.0
(7.2 to 30.9)
HbA1c <6.5%: Week 28
23.1
(13.7 to 32.4)
14.3
(3.7 to 24.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Total Exenatide Twice Daily (EBID), Placebo
Comments

Treatment difference in HbA1c < 7% at Week 28:

Treatment group comparison is based on CMH test stratified by screening HbA1c and background diabetes therapy strata. P-value is from the general association statistics.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.562
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Total Exenatide Twice Daily (EBID), Placebo
Comments

Treatment difference in HbA1c <= 6.5% at Week 28:

Treatment group comparison is based on CMH test stratified by screening HbA1c and background diabetes therapy strata. P-value is from the general association statistics.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.621
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Total Exenatide Twice Daily (EBID), Placebo
Comments

Treatment difference in HbA1c < 6.5% at Week 28:

Treatment group comparison is based on CMH test stratified by screening HbA1c and background diabetes therapy strata. P-value is from the general association statistics.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.229
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
4.Secondary Outcome
Title Adjusted Change From Baseline in Body Weight Through Week 28
Hide Description 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.
Time Frame Baseline (Day 1) up to Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set included all randomized participants who received at least 1 dose of randomized study medication. For analysis of efficacy, a decision was made with agreement by the European Medicines Agency and the Food and Drug Administration to pool participants from both exenatide groups (Total EBID) and compare this pooled group with placebo.
Arm/Group Title Total Exenatide Twice Daily (EBID) Placebo
Hide Arm/Group Description:

Efficacy data from participants from both exenatide groups (Total EBID) was pooled for comparison with placebo.

Adolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks; or Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks.

Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
Overall Number of Participants Analyzed 78 42
Least Squares Mean (Standard Error)
Unit of Measure: kilogram
Week 4 -0.89  (0.196) 0.04  (0.260)
Week 12 -1.09  (0.401) -0.42  (0.534)
Week 20 -0.71  (0.559) -0.33  (0.755)
Week 28 -0.81  (0.632) -0.36  (0.857)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Total Exenatide Twice Daily (EBID), Placebo
Comments

Treatment difference in body weight at Week 4:

Adjusted LS mean and treatment group difference in the change from baseline values at visit are obtained from a MMRM including treatment, baseline body weight, screening HbA1c strata, background diabetes therapy strata, week of visit, baseline body weight-by visit interaction and treatment-by-visit interaction as fixed effects using an unstructured covariance matrix.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.93
Confidence Interval (2-Sided) 95%
-1.58 to -0.28
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.327
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Total Exenatide Twice Daily (EBID), Placebo
Comments

Treatment difference in body weight at Week 12:

Adjusted LS mean and treatment group difference in the change from baseline values at visit are obtained from a MMRM including treatment, baseline body weight, screening HbA1c strata, background diabetes therapy strata, week of visit, baseline body weight-by visit interaction and treatment-by-visit interaction as fixed effects using an unstructured covariance matrix.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.314
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.68
Confidence Interval (2-Sided) 95%
-2.00 to 0.65
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.669
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Total Exenatide Twice Daily (EBID), Placebo
Comments

Treatment difference in body weight at Week 20:

Adjusted LS mean and treatment group difference in the change from baseline values at visit are obtained from a MMRM including treatment, baseline body weight, screening HbA1c strata, background diabetes therapy strata, week of visit, baseline body weight-by visit interaction and treatment-by-visit interaction as fixed effects using an unstructured covariance matrix.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.692
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.37
Confidence Interval (2-Sided) 95%
-2.24 to 1.50
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.940
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Total Exenatide Twice Daily (EBID), Placebo
Comments

Treatment difference in body weight at Week 28:

Adjusted LS mean and treatment group difference in the change from baseline values at visit are obtained from a MMRM including treatment, baseline body weight, screening HbA1c strata, background diabetes therapy strata, week of visit, baseline body weight-by visit interaction and treatment-by-visit interaction as fixed effects using an unstructured covariance matrix.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.679
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.44
Confidence Interval (2-Sided) 95%
-2.56 to 1.68
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.065
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Adjusted Change From Baseline in Fasting Serum Glucose (FSG) at Week 28
Hide Description 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.
Time Frame Baseline (Day 1) and Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set included all randomized participants who received at least 1 dose of randomized study medication. For analysis of efficacy, a decision was made with agreement by the European Medicines Agency and the Food and Drug Administration to pool participants from both exenatide groups (Total EBID) and compare this pooled group with placebo.
Arm/Group Title Total Exenatide Twice Daily (EBID) Placebo
Hide Arm/Group Description:

Efficacy data from participants from both exenatide groups (Total EBID) was pooled for comparison with placebo.

Adolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks; or Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks.

Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
Overall Number of Participants Analyzed 78 42
Least Squares Mean (Standard Error)
Unit of Measure: millimoles per liter (mmol/L)
0.791  (0.4010) 1.072  (0.5466)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Total Exenatide Twice Daily (EBID), Placebo
Comments Adjusted LS Mean and treatment group difference in the change from baseline values at Week 28 are obtained from multiple imputation ANCOVA including treatment, baseline fasting serum glucose, screening HbA1c strata and background diabetes therapy strata as fixed effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.679
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.281
Confidence Interval (2-Sided) 95%
-1.614 to 1.052
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.6800
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Adjusted Change From Baseline in Self-Monitored Blood Glucose (SMBG) at Week 28
Hide Description 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.
Time Frame Pre-meal and 2 hours post-meal on Baseline (Day 1) and Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set included all randomized participants who received at least 1 dose of randomized study medication. For analysis of efficacy, a decision was made with agreement by the European Medicines Agency and the Food and Drug Administration to pool participants from both exenatide groups (Total EBID) and compare this pooled group with placebo.
Arm/Group Title Total Exenatide Twice Daily (EBID) Placebo
Hide Arm/Group Description:

Efficacy data from participants from both exenatide groups (Total EBID) was pooled for comparison with placebo.

Adolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks; or Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks.

Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
Overall Number of Participants Analyzed 78 42
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
Pre-meal SMBG -0.699  (0.2709) -0.888  (0.4511)
Post-meal SMBG -1.029  (0.2722) -1.542  (0.4503)
Post-prandial excursion SMBG -0.181  (0.2107) -0.391  (0.3418)
Overall SMBG -0.877  (0.2468) -1.193  (0.4117)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Total Exenatide Twice Daily (EBID), Placebo
Comments Treatment difference for pre-meal SMBG: Adjusted LS Mean and treatment group difference in the change from baseline values at Week 28 are obtained from multiple imputation ANCOVA including treatment, baseline SMBG measure, screening HbA1c strata and background diabetes therapy strata as fixed effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.714
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.189
Confidence Interval (2-Sided) 95%
-0.821 to 1.199
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.5151
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Total Exenatide Twice Daily (EBID), Placebo
Comments Treatment difference for post-meal SMBG: Adjusted LS Mean and treatment group difference in the change from baseline values at Week 28 are obtained from multiple imputation ANCOVA including treatment, baseline SMBG measure, screening HbA1c strata and background diabetes therapy strata as fixed effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.329
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.513
Confidence Interval (2-Sided) 95%
-0.516 to 1.541
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.5245
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Total Exenatide Twice Daily (EBID), Placebo
Comments Treatment difference for post-prandial excursion SMBG: Adjusted LS Mean and treatment group difference in the change from baseline values at Week 28 are obtained from multiple imputation ANCOVA including treatment, baseline SMBG measure, screening HbA1c strata and background diabetes therapy strata as fixed effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.601
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.210
Confidence Interval (2-Sided) 95%
-0.577 to 0.997
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.4015
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Total Exenatide Twice Daily (EBID), Placebo
Comments Treatment difference for overall SMBG: Adjusted LS Mean and treatment group difference in the change from baseline values at Week 28 are obtained from multiple imputation ANCOVA including treatment, baseline SMBG measure, screening HbA1c strata and background diabetes therapy strata as fixed effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.505
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.316
Confidence Interval (2-Sided) 95%
-0.615 to 1.248
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.4749
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Adjusted Change From Baseline in Fasting Serum Insulin at Week 28
Hide Description 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.
Time Frame Baseline (Day 1) and Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set included all randomized participants who received at least 1 dose of randomized study medication. For analysis of efficacy, a decision was made with agreement by the European Medicines Agency and the Food and Drug Administration to pool participants from both exenatide groups (Total EBID) and compare this pooled group with placebo.
Arm/Group Title Total Exenatide Twice Daily (EBID) Placebo
Hide Arm/Group Description:

Efficacy data from participants from both exenatide groups (Total EBID) was pooled for comparison with placebo.

Adolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks; or Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks.

Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
Overall Number of Participants Analyzed 78 42
Least Squares Mean (Standard Error)
Unit of Measure: picomoles per liter
1.67  (25.323) 12.49  (34.825)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Total Exenatide Twice Daily (EBID), Placebo
Comments Adjusted LS Mean and treatment group difference in the change from baseline values at Week 28 are obtained from multiple imputation ANCOVA including treatment, baseline fasting serum insulin, screening HbA1c strata and background diabetes therapy strata as fixed effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.802
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -10.82
Confidence Interval (2-Sided) 95%
-95.48 to 73.84
Parameter Dispersion
Type: Standard Error of the Mean
Value: 43.187
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Adjusted Change From Baseline in Homeostasis Model Assessments - Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) at Week 28
Hide Description 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.
Time Frame Baseline (Day 1) and Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set included all randomized participants who received at least 1 dose of randomized study medication. For analysis of efficacy, a decision was made with agreement by the European Medicines Agency and the Food and Drug Administration to pool participants from both exenatide groups (Total EBID) and compare this pooled group with placebo.
Arm/Group Title Total Exenatide Twice Daily (EBID) Placebo
Hide Arm/Group Description:

Efficacy data from participants from both exenatide groups (Total EBID) was pooled for comparison with placebo.

Adolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks; or Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks.

Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
Overall Number of Participants Analyzed 78 42
Least Squares Mean (Standard Error)
Unit of Measure: percentage (%HOMA-B and %HOMA-S)
HOMA-B -25.93  (10.404) -22.10  (14.885)
HOMA-S -3.18  (2.172) -2.90  (3.117)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Total Exenatide Twice Daily (EBID), Placebo
Comments Treatment difference for HOMA-B: Adjusted LS Mean and treatment group difference in the change from baseline values at Week 28 are obtained from multiple imputation ANCOVA including treatment, baseline %HOMA-B, screening HbA1c strata and background diabetes therapy strata as fixed effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.836
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.84
Confidence Interval (2-Sided) 95%
-40.19 to 32.51
Parameter Dispersion
Type: Standard Error of the Mean
Value: 18.542
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Total Exenatide Twice Daily (EBID), Placebo
Comments Treatment difference for HOMA-S: Adjusted LS Mean and treatment group difference in the change from baseline values at Week 28 are obtained from multiple imputation ANCOVA including treatment, baseline %HOMA-S, screening HbA1c strata and background diabetes therapy strata as fixed effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.941
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-7.82 to 7.26
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.846
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Percentage of Participants Discontinuing the Study Due to Failure to Maintain Glycemic Control Through Week 28
Hide Description 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.
Time Frame Weeks 2, 4, 8, 12, 16, 20, 24 and 28
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set included all randomized participants who received at least 1 dose of randomized study medication. For analysis of efficacy, a decision was made with agreement by the European Medicines Agency and the Food and Drug Administration to pool participants from both exenatide groups (Total EBID) and compare this pooled group with placebo.
Arm/Group Title Total Exenatide Twice Daily (EBID) Placebo
Hide Arm/Group Description:

Efficacy data from participants from both exenatide groups (Total EBID) was pooled for comparison with placebo.

Adolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks; or Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks.

Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
Overall Number of Participants Analyzed 78 42
Measure Type: Number
Unit of Measure: percentage of participants
Week 2 Number Analyzed 78 participants 42 participants
0 0
Week 4 Number Analyzed 78 participants 42 participants
0 2.4
Week 8 Number Analyzed 78 participants 41 participants
0 0
Week 12 Number Analyzed 78 participants 40 participants
1.4 5.0
Week 16 Number Analyzed 78 participants 36 participants
1.4 0
Week 20 Number Analyzed 78 participants 34 participants
0 14.7
Week 24 Number Analyzed 78 participants 29 participants
0 6.9
Week 28 Number Analyzed 78 participants 26 participants
1.6 0
Time Frame Serious AEs: From first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 32 weeks. Non-serious AEs: From first dose of study drug (Day 1) up to 1 day after last dose of study drug, approximately 28 weeks.
Adverse Event Reporting Description

The Safety Analysis Set included all participants who received at least 1 dose of randomized study medication.

Treatment-emergent AEs (TEAEs) are reported. A TEAE was defined as an AE starting (or worsening) after the first dose of randomized study medication through the end of treatment + 1 day for non-serious AEs or + 30 days for serious AEs.

 
Arm/Group Title Exenatide 5 mcg Exenatide 10 mcg Placebo
Hide Arm/Group Description Adolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks. Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks. Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks.
All-Cause Mortality
Exenatide 5 mcg Exenatide 10 mcg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/41 (0.00%)      0/37 (0.00%)      0/42 (0.00%)    
Hide Serious Adverse Events
Exenatide 5 mcg Exenatide 10 mcg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/41 (7.32%)      1/37 (2.70%)      1/42 (2.38%)    
Infections and infestations       
Cellulitis  1  1/41 (2.44%)  1 0/37 (0.00%)  0 0/42 (0.00%)  0
Gastroenteritis  1  1/41 (2.44%)  1 0/37 (0.00%)  0 1/42 (2.38%)  1
Gastroenteritis viral  1  0/41 (0.00%)  0 0/37 (0.00%)  0 1/42 (2.38%)  1
Staphylococcal abscess  1  1/41 (2.44%)  1 0/37 (0.00%)  0 0/42 (0.00%)  0
Pregnancy, puerperium and perinatal conditions       
Pregnancy  1  0/41 (0.00%)  0 1/37 (2.70%)  1 0/42 (0.00%)  0
Psychiatric disorders       
Intentional self-injury  1  1/41 (2.44%)  1 0/37 (0.00%)  0 0/42 (0.00%)  0
1
Term from vocabulary, MedDRA 23.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Exenatide 5 mcg Exenatide 10 mcg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   26/41 (63.41%)      24/37 (64.86%)      23/42 (54.76%)    
Ear and labyrinth disorders       
Ear pain  1  2/41 (4.88%)  2 2/37 (5.41%)  2 3/42 (7.14%)  3
Gastrointestinal disorders       
Abdominal pain upper  1  1/41 (2.44%)  1 2/37 (5.41%)  5 2/42 (4.76%)  4
Diarrhoea  1  2/41 (4.88%)  3 3/37 (8.11%)  3 5/42 (11.90%)  9
Nausea  1  4/41 (9.76%)  4 11/37 (29.73%)  15 7/42 (16.67%)  10
Vomiting  1  2/41 (4.88%)  2 8/37 (21.62%)  10 3/42 (7.14%)  3
General disorders       
Pyrexia  1  2/41 (4.88%)  2 1/37 (2.70%)  1 3/42 (7.14%)  3
Infections and infestations       
Furuncle  1  0/41 (0.00%)  0 2/37 (5.41%)  2 0/42 (0.00%)  0
Influenza  1  3/41 (7.32%)  3 0/37 (0.00%)  0 0/42 (0.00%)  0
Nasopharyngitis  1  8/41 (19.51%)  10 2/37 (5.41%)  4 3/42 (7.14%)  3
Pharyngitis  1  4/41 (9.76%)  6 2/37 (5.41%)  5 1/42 (2.38%)  1
Pharyngitis streptococcal  1  0/41 (0.00%)  0 2/37 (5.41%)  2 0/42 (0.00%)  0
Sinusitis  1  4/41 (9.76%)  4 1/37 (2.70%)  1 2/42 (4.76%)  2
Upper respiratory tract infection  1  5/41 (12.20%)  8 3/37 (8.11%)  3 5/42 (11.90%)  9
Musculoskeletal and connective tissue disorders       
Back pain  1  1/41 (2.44%)  1 2/37 (5.41%)  4 2/42 (4.76%)  2
Nervous system disorders       
Dizziness  1  2/41 (4.88%)  2 2/37 (5.41%)  3 2/42 (4.76%)  2
Headache  1  9/41 (21.95%)  14 9/37 (24.32%)  15 11/42 (26.19%)  27
Reproductive system and breast disorders       
Dysmenorrhoea  1  2/41 (4.88%)  3 3/37 (8.11%)  4 4/42 (9.52%)  6
Respiratory, thoracic and mediastinal disorders       
Oropharyngeal pain  1  3/41 (7.32%)  3 0/37 (0.00%)  0 3/42 (7.14%)  3
1
Term from vocabulary, MedDRA 23.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Clinical Lead
Organization: AstraZeneca
Phone: 1-877-240-9479
EMail: information.center@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00658021    
Other Study ID Numbers: D5550C00002
H8O-MC-GWBQ ( Other Identifier: company identifier )
First Submitted: April 8, 2008
First Posted: April 14, 2008
Results First Submitted: September 23, 2020
Results First Posted: December 1, 2020
Last Update Posted: December 1, 2020