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Exenatide Compared With Twice-Daily Biphasic Insulin Aspart in Patients With Type 2 Diabetes Using Sulfonylurea and Metformin

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ClinicalTrials.gov Identifier: NCT00082407
Recruitment Status : Completed
First Posted : May 10, 2004
Results First Posted : July 31, 2013
Last Update Posted : April 7, 2015
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 2
Interventions Drug: exenatide
Drug: biphasic insulin aspart
Enrollment 505
Recruitment Details  
Pre-assignment Details Four patients withdrew from the study prior to receiving study drug.
Arm/Group Title Exenatide Arm Biphasic Insulin Aspart Arm
Hide Arm/Group Description subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks subcutaneous injection, twice daily; titration to target blood glucose level
Period Title: Overall Study
Started 255 250
Received Treatment (Intent to Treat) 253 248
Completed 199 223
Not Completed 56 27
Reason Not Completed
Adverse Event             20             0
Protocol Violation             14             12
Patient Decision             13             6
Physician Decision             5             3
Loss of Glucose Control             2             2
Death             2             1
Lost to Follow-up             0             3
Arm/Group Title Exenatide Arm Biphasic Insulin Aspart Arm Total
Hide Arm/Group Description subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks subcutaneous injection, twice daily; titration to target blood glucose level Total of all reporting groups
Overall Number of Baseline Participants 253 248 501
Hide Baseline Analysis Population Description
IIT population
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 253 participants 248 participants 501 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
184
  72.7%
174
  70.2%
358
  71.5%
>=65 years
69
  27.3%
74
  29.8%
143
  28.5%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 253 participants 248 participants 501 participants
58.8  (8.7) 58.5  (9.2) 58.7  (9.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 253 participants 248 participants 501 participants
Female
135
  53.4%
122
  49.2%
257
  51.3%
Male
118
  46.6%
126
  50.8%
244
  48.7%
1.Primary Outcome
Title Change in Glcosylated Hemoglobin (HbA1c)
Hide Description Change in HbA1c from baseline to week 52
Time Frame baseline, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Last Observation Carried Forward; Intent to Treat, computed from the patients having both baseline and post-baseline data.
Arm/Group Title Exenatide Arm Biphasic Insulin Aspart Arm
Hide Arm/Group Description:
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
subcutaneous injection, twice daily; titration to target blood glucose level
Overall Number of Participants Analyzed 248 246
Least Squares Mean (Standard Error)
Unit of Measure: percentage
Baseline HbA1c 8.59  (0.07) 8.65  (0.07)
Change in HbA1c at week 52 -0.98  (0.07) -0.88  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide Arm, Biphasic Insulin Aspart Arm
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Pre-specified non-inferiority margin was 0.4% (i.e., noninferiority is demonstrated if the upper limit of a two-sided 95% confidence interval for the difference in change in HbA1c between exenatide and biphasic insulin aspart is less than 0.4%.)
Statistical Test of Hypothesis P-Value 0.2534
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.10
Confidence Interval 95%
-0.28 to 0.08
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Patients Achieving HbA1c <=7%
Hide Description Percentage of patients in each arm who had HbA1c >7% at baseline and had HbA1c <=7% at week 52 (percentage = [number of subjects with HbA1c <=7% at week 52 divided by number of subjects with HbA1c >7% at baseline] * 100%).
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Last Observation Carried Forward; Intent to Treat
Arm/Group Title Exenatide Arm Biphasic Insulin Aspart Arm
Hide Arm/Group Description:
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
subcutaneous injection, twice daily; titration to target blood glucose level
Overall Number of Participants Analyzed 227 237
Measure Type: Number
Unit of Measure: percentage of participants
31.7 24.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide Arm, Biphasic Insulin Aspart Arm
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0779
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Change in Body Weight
Hide Description Change in body weight from baseline to week 52.
Time Frame baseline, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat, computed from the patients having both baseline and week 52 data.
Arm/Group Title Exenatide Arm Biphasic Insulin Aspart Arm
Hide Arm/Group Description:
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
subcutaneous injection, twice daily; titration to target blood glucose level
Overall Number of Participants Analyzed 205 223
Least Squares Mean (Standard Error)
Unit of Measure: kg
Baseline body weight 85.51  (0.99) 83.38  (0.99)
Change in body weight at week 52 -2.54  (0.17) 2.92  (0.17)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide Arm, Biphasic Insulin Aspart Arm
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
4.Secondary Outcome
Title Change in Fasting Serum Glucose
Hide Description Change in fasting serum glucose from baseline to week 52
Time Frame baseline, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat, computed from the patients having both baseline and week 52 data.
Arm/Group Title Exenatide Arm Biphasic Insulin Aspart Arm
Hide Arm/Group Description:
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
subcutaneous injection, twice daily; titration to target blood glucose level
Overall Number of Participants Analyzed 198 218
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
Baseline fasting serum glucose 11.00  (0.18) 11.30  (0.18)
Change in fasting serum glucose at week 52 -1.75  (0.19) -1.64  (0.19)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide Arm, Biphasic Insulin Aspart Arm
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6456
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
5.Secondary Outcome
Title Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
Hide Description Change in 7-point (pre-breakfast, after breakfast, pre-lunch, after lunch, pre-dinner, after dinner, 0300 hours) SMBG profile from baseline to week 52
Time Frame baseline, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Last Observation Carried Forward; Intent to Treat
Arm/Group Title Exenatide Arm Biphasic Insulin Aspart Arm
Hide Arm/Group Description:
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
subcutaneous injection, twice daily; titration to target blood glucose level
Overall Number of Participants Analyzed 253 248
Mean (Standard Deviation)
Unit of Measure: mmol/L
Pre-breakfast: Baseline SMBG 9.57  (2.34) 9.86  (2.65)
Pre-breakfast: Change in SMBG at week 52 -1.15  (2.60) -1.68  (2.33)
After breakfast: Baseline SMBG 12.30  (3.02) 12.71  (3.03)
After breakfast: Change in SMBG at week 52 -3.83  (3.30) -3.06  (3.26)
Pre-lunch: Baseline SMBG 9.38  (2.86) 9.86  (3.30)
Pre-lunch: Change in SMBG at week 52 -1.47  (3.01) -2.40  (3.44)
After lunch: Baseline SMBG 11.18  (3.14) 11.39  (3.58)
After lunch: Change in SMBG at week 52 -1.72  (3.48) -1.76  (3.74)
Pre-dinner: Baseline SMBG 9.35  (2.86) 9.57  (3.03)
Pre-dinner: Change in SMBG at week 52 -1.06  (3.25) -1.52  (3.42)
After dinner: Baseline SMBG 11.25  (3.04) 11.68  (3.27)
After dinner: Change in SMBG at week 52 -3.11  (3.76) -2.44  (3.69)
3:00 AM: Baseline SMBG 9.08  (2.63) 9.58  (3.14)
3:00 AM: Change in SMBG at week 52 -0.96  (3.14) -1.95  (3.13)
6.Secondary Outcome
Title Percentage of Patients With Hypoglycemic Events
Hide Description Percentage of patients who experienced at least one episode of hypoglycemia at any point during the 52 week Parent Study (incidence of hypoglycemia = number of patients who experienced at least one episode of hypoglycemia at any point during the 52 week Parent Study divided by the total number of patients who particiapted in the 52 week Parent Study
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat
Arm/Group Title Exenatide Arm Biphasic Insulin Aspart Arm
Hide Arm/Group Description:
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
subcutaneous injection, twice daily; titration to target blood glucose level
Overall Number of Participants Analyzed 253 248
Measure Type: Number
Unit of Measure: percentage of participants
53.0 51.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide Arm, Biphasic Insulin Aspart Arm
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7888
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
7.Secondary Outcome
Title Change in Rate of Hypoglycemic Events
Hide Description Change in rate of hypoglycemic events per 30 days per patient from baseline to week 52
Time Frame baseline, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Last Observation Carried Forward; Intent to Treat
Arm/Group Title Exenatide Arm Biphasic Insulin Aspart Arm
Hide Arm/Group Description:
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
subcutaneous injection, twice daily; titration to target blood glucose level
Overall Number of Participants Analyzed 253 248
Least Squares Mean (Standard Error)
Unit of Measure: events per 30 days per patient
Baseline event rate 0.22  (0.07) 0.18  (0.07)
Change in event rate at week 52 0.19  (0.06) 0.26  (0.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Exenatide Arm, Biphasic Insulin Aspart Arm
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3722
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Exenatide Arm Biphasic Insulin Aspart Arm
Hide Arm/Group Description subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks subcutaneous injection, twice daily; titration to target blood glucose level
All-Cause Mortality
Exenatide Arm Biphasic Insulin Aspart Arm
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Exenatide Arm Biphasic Insulin Aspart Arm
Affected / at Risk (%) Affected / at Risk (%)
Total   19   11 
Blood and lymphatic system disorders     
Anemia  1  2/253 (0.79%)  0/248 (0.00%) 
Cardiac disorders     
Angina pectoris  1  2/253 (0.79%)  0/248 (0.00%) 
Myocardial infarction  1  2/253 (0.79%)  0/248 (0.00%) 
Atrial fibrillation  1  1/253 (0.40%)  0/248 (0.00%) 
Coronary artery disease  1  1/253 (0.40%)  0/248 (0.00%) 
Acute coronary syndrome  1  0/253 (0.00%)  1/248 (0.40%) 
Atrial flutter  1  0/253 (0.00%)  1/248 (0.40%) 
Bundle branch block left  1  0/253 (0.00%)  1/248 (0.40%) 
Ear and labyrinth disorders     
Vertigo  1  0/253 (0.00%)  1/248 (0.40%) 
Gastrointestinal disorders     
Gastrointestinal hemorrhage  1  1/253 (0.40%)  0/248 (0.00%) 
Nausea  1  1/253 (0.40%)  0/248 (0.00%) 
Anal fistula  1  0/253 (0.00%)  1/248 (0.40%) 
General disorders     
Asthenia  1  1/253 (0.40%)  0/248 (0.00%) 
Calcinosis  1  1/253 (0.40%)  0/248 (0.00%) 
Gait disturbance  1  1/253 (0.40%)  0/248 (0.00%) 
Infections and infestations     
Abdominal wall abscess  1  1/253 (0.40%)  0/248 (0.00%) 
Appendicitis  1  1/253 (0.40%)  0/248 (0.00%) 
Cellulitus  1  1/253 (0.40%)  0/248 (0.00%) 
Injection site cellulitus  1  1/253 (0.40%)  0/248 (0.00%) 
Lobar pneumonia  1  0/253 (0.00%)  1/248 (0.40%) 
Injury, poisoning and procedural complications     
Fall  1  1/253 (0.40%)  0/248 (0.00%) 
Radius fracture  1  1/253 (0.40%)  0/248 (0.00%) 
Investigations     
Weight decreased  1  1/253 (0.40%)  0/248 (0.00%) 
Metabolism and nutrition disorders     
Anorexia  1  1/253 (0.40%)  0/248 (0.00%) 
Musculoskeletal and connective tissue disorders     
Osteoarthritis  1  2/253 (0.79%)  0/248 (0.00%) 
Musculoskeletal pain  1  1/253 (0.40%)  0/248 (0.00%) 
Neck pain  1  0/253 (0.00%)  1/248 (0.40%) 
Spinal osteoarthritis  1  0/253 (0.00%)  1/248 (0.40%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Fibroadenoma of breast  1  0/253 (0.00%)  1/248 (0.40%) 
Prostate cancer  1  0/253 (0.00%)  1/248 (0.40%) 
Nervous system disorders     
Cognitive disorder  1  1/253 (0.40%)  0/248 (0.00%) 
Cerebrovascular accident  1  0/253 (0.00%)  1/248 (0.40%) 
Psychiatric disorders     
Major depression  1  1/253 (0.40%)  0/248 (0.00%) 
Renal and urinary disorders     
Urinary incontinence  1  0/253 (0.00%)  1/248 (0.40%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  1/253 (0.40%)  0/248 (0.00%) 
Breast microcalcification  1  0/253 (0.00%)  1/248 (0.40%) 
Respiratory, thoracic and mediastinal disorders     
Pharyngeal mass  1  1/253 (0.40%)  0/248 (0.00%) 
Pulmonary edema  1  0/253 (0.00%)  1/248 (0.40%) 
Vascular disorders     
Hematoma  1  1/253 (0.40%)  0/248 (0.00%) 
Hypertension  1  1/253 (0.40%)  0/248 (0.00%) 
Peripheral ischemia  1  1/253 (0.40%)  0/248 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA8.0/11.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Exenatide Arm Biphasic Insulin Aspart Arm
Affected / at Risk (%) Affected / at Risk (%)
Total   179   128 
Gastrointestinal disorders     
Nausea  1  84/253 (33.20%)  1/248 (0.40%) 
Vomiting  1  38/253 (15.02%)  8/248 (3.23%) 
Diarrhea  1  24/253 (9.49%)  5/248 (2.02%) 
Infections and infestations     
Nasopharyngitis  1  28/253 (11.07%)  24/248 (9.68%) 
Influenza  1  18/253 (7.11%)  16/248 (6.45%) 
Metabolism and nutrition disorders     
Hypoglycemia  1  134/253 (52.96%)  128/248 (51.61%) 
Nervous system disorders     
Headache  1  12/253 (4.74%)  13/248 (5.24%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA8.0/11.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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: Peter Ohman, Medical Science Director
Organization: AstraZeneca
EMail: ClinicalTrialTransparency@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00082407     History of Changes
Other Study ID Numbers: H8O-MC-GWAD
First Submitted: May 6, 2004
First Posted: May 10, 2004
Results First Submitted: July 16, 2009
Results First Posted: July 31, 2013
Last Update Posted: April 7, 2015