Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Effects of Exenatide Long-Acting Release on Glucose Control and Safety in Subjects With Type 2 Diabetes Mellitus(DURATION - 1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00308139
First received: March 27, 2006
Last updated: July 29, 2015
Last verified: July 2015
Results First Received: February 14, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Type 2 Diabetes Mellitus
Interventions: Drug: exenatide, long acting release
Drug: exenatide

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Exenatide Once Weekly -> Exenatide Once Weekly Subcutaneous injection of 2 mg exenatide, once a week.
Exenatide Twice Daily -> Exenatide Once Weekly Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 26 weeks) followed by 2 mg exenatide, once a week.

Participant Flow:   Overall Study
    Exenatide Once Weekly -> Exenatide Once Weekly   Exenatide Twice Daily -> Exenatide Once Weekly
STARTED   152   151 
Intent to Treat (ITT)   148 [1]   147 [1] 
ITT in the 30-Week Assessment   148 [2]   145 [2] 
Pharmacokinetics Population   129   0 
Evaluable Meal Tolerance Cohort   27   24 
30-Week Completed   128 [3]   130 [3] 
COMPLETED   58 [4]   64 [4] 
NOT COMPLETED   94   87 
Adverse Event                20                14 
Lost to Follow-up                13                8 
Protocol Violation                3                2 
Withdrawal of Consent                40                42 
Investigator Decision                11                10 
Loss of Glucose Control                5                7 
Administrative                1                4 
Other                1                0 
[1] Subjects who received at least one injection of lead-in exenatide 5 mcg.
[2] ITT Subjects who received at least one injection of randomized dose.
[3] Subjects who completed 30 weeks of assessment
[4] Subjects who completed 364 weeks of assessment



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Exenatide Once Weekly -> Exenatide Once Weekly Subcutaneous injection of 2 mg exenatide, once a week.
Exenatide Twice Daily -> Exenatide Once Weekly Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 26 weeks) followed by 2 mg exenatide, once a week.
Total Total of all reporting groups

Baseline Measures
   Exenatide Once Weekly -> Exenatide Once Weekly   Exenatide Twice Daily -> Exenatide Once Weekly   Total 
Overall Participants Analyzed 
[Units: Participants]
 148   147   295 
Age 
[Units: Participants]
     
<=18 years   0   0   0 
Between 18 and 65 years   122   123   245 
>=65 years   26   24   50 
Age 
[Units: Years]
Mean (Standard Deviation)
 55.2  (9.72)   54.9  (9.63)   55.0  (9.66) 
Gender 
[Units: Participants]
     
Female   66   72   138 
Male   82   75   157 
Glycosylated hemoglobin (HbA1c) 
[Units: Percentage of total hemoglobin]
Mean (Standard Deviation)
 8.3  (0.99)   8.3  (1.00)   8.3  (0.99) 
Weight 
[Units: Kg]
Mean (Standard Deviation)
 101.7  (18.76)   101.9  (21.05)   101.8  (19.90) 
Background Oral Antidiabetic Agent 
[Units: Participants]
     
Diet and Exercise   21   22   43 
Metformin (MET)   56   50   106 
Sulfonylurea (SU)   6   10   16 
Thiazolidinediones (TZD)   2   7   9 
MET+SU   43   39   82 
MET+TZD   14   14   28 
SU+TZD   5   5   10 
SU+MET+TZD   1   0   1 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change in HbA1c From Baseline to Week 30   [ Time Frame: Day -3, Week 30 ]

2.  Secondary:   Change in HbA1c From Baseline to Week 364   [ Time Frame: Day -3, Week 364 ]

3.  Secondary:   Percentage of Subjects Achieving HbA1c Target of <7%   [ Time Frame: Week 30 ]

4.  Secondary:   Percentage of Subjects Achieving HbA1c Target of <7%   [ Time Frame: Week 364 ]

5.  Secondary:   Percentage of Subjects Achieving HbA1c Target of <=6.5%   [ Time Frame: Week 30 ]

6.  Secondary:   Percentage of Subjects Achieving HbA1c Target of <=6.5%   [ Time Frame: Week 364 ]

7.  Secondary:   Percentage of Subjects Achieving HbA1c Target of <=6.0%   [ Time Frame: Week 30 ]

8.  Secondary:   Exenatide LAR Steady State Concentration From Week 29 to Week 30   [ Time Frame: Week 29 to Week 30 ]

9.  Secondary:   Change in 2 Hours (2h) Postprandial Glucose From Baseline to Week 14   [ Time Frame: Day -3, Week 14 ]

10.  Secondary:   Change in Body Weight From Baseline to Week 30   [ Time Frame: Day -3, Week 30 ]

11.  Secondary:   Change in Body Weight From Baseline to Week 364   [ Time Frame: Day -3, Week 364 ]

12.  Secondary:   Change in Fasting Plasma Glucose From Baseline to Week 30   [ Time Frame: Day -3, Week 30 ]

13.  Secondary:   Change in Fasting Plasma Glucose From Baseline to Week 364   [ Time Frame: Day -3, Week 364 ]

14.  Secondary:   Change in Blood Pressure From Baseline to Week 30   [ Time Frame: Day -3, Week 30 ]

15.  Secondary:   Change in Blood Pressure From Baseline to Week 364   [ Time Frame: Day -3, Week 364 ]

16.  Secondary:   Change in Total Cholesterol From Baseline to Week 30   [ Time Frame: Day -3, Week 30 ]

17.  Secondary:   Change in Total Cholesterol From Baseline to Week 364   [ Time Frame: Day -3, Week 364 ]

18.  Secondary:   Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 30   [ Time Frame: Day -3, Week 30 ]

19.  Secondary:   Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 364   [ Time Frame: Day -3, Week 364 ]

20.  Secondary:   Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 364   [ Time Frame: Day -3, Week 364 ]

21.  Secondary:   Ratio of Triglycerides at Week 30 to Baseline   [ Time Frame: Day -3, Week 30 ]

22.  Secondary:   Ratio of Triglycerides at Week 364 to Baseline   [ Time Frame: Day -3, Week 364 ]

23.  Secondary:   Assessment on Event Rate of Treatment-emergent Hypoglycemic Events With SU Use at Screening   [ Time Frame: Day 1 to Week 364 ]

24.  Secondary:   Assessment on Event Rate of Treatment-emergent Hypoglycemic Events With Non-SU Use at Screening   [ Time Frame: Day 1 to Week 364 ]

25.  Primary:   Sub-study Relative Bioavailability of Exenatide When Administered Using the Exenatide Once Weekly Dual Chambered Pen and the Exenatide Once Weekly Single Dose Tray (Single Dose Tray-11 Weekly Doses Switch to Dual Chamber Pen-11 Weekly Dose)   [ Time Frame: Week 22 ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

26.  Secondary:   Sub-study Safety and Tolerability of Exenatide When Administered Using the Once Weekly Single Dose Tray and the Once Weekly Dual (Single Dose Tray-11 Weekly Doses Switch to Dual Chamber Pen-11 Weekly Dose)   [ Time Frame: Week 22 ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   Yes


  Serious Adverse Events


  Other Adverse Events
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Time Frame No text entered.
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   5  

Reporting Groups
  Description
Exenatide Once Weekly (WK 0-30) Subcutaneous injection of 2 mg exenatide, once a week.
Exenatide Twice Daily (WK 0-30) Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 26 weeks).
Exenatide Once Weekly -> Exenatide Once Weekly (WK 31-364) Subcutaneous injection of 2 mg exenatide, once a week.
Exenatide Twice Daily -> Exenatide Once Weekly (WK 31-364) Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 26 weeks) followed by 2 mg exenatide, once a week.
Exenatide Once Weekly Subcutaneous injection of 2 mg exenatide, once a week. Pooling unique subjects from exenatide once weekly (WK 0-30), exenatide once weekly -> exenatide once weekly (WK 31-364), and exenatide twice daily -> exenatide once weekly (WK 31-364).

Other Adverse Events
    Exenatide Once Weekly (WK 0-30)   Exenatide Twice Daily (WK 0-30)   Exenatide Once Weekly -> Exenatide Once Weekly (WK 31-364)   Exenatide Twice Daily -> Exenatide Once Weekly (WK 31-364)   Exenatide Once Weekly
Total, other (not including serious) adverse events           
# participants affected / at risk   124/148 (83.78%)   106/145 (73.10%)   121/128 (94.53%)   122/130 (93.85%)   265/278 (95.32%) 
Blood and lymphatic system disorders           
Anaemia           
# participants affected / at risk   2/148 (1.35%)   2/145 (1.38%)   8/128 (6.25%)   5/130 (3.85%)   15/278 (5.40%) 
Eye disorders           
Cataract           
# participants affected / at risk   2/148 (1.35%)   0/145 (0.00%)   15/128 (11.72%)   9/130 (6.92%)   25/278 (8.99%) 
Gastrointestinal disorders           
Nausea           
# participants affected / at risk   40/148 (27.03%)   49/145 (33.79%)   26/128 (20.31%)   25/130 (19.23%)   82/278 (29.50%) 
Diarrhoea           
# participants affected / at risk   24/148 (16.22%)   18/145 (12.41%)   35/128 (27.34%)   34/130 (26.15%)   79/278 (28.42%) 
Constipation           
# participants affected / at risk   15/148 (10.14%)   9/145 (6.21%)   11/128 (8.59%)   16/130 (12.31%)   40/278 (14.39%) 
Vomiting           
# participants affected / at risk   16/148 (10.81%)   27/145 (18.62%)   21/128 (16.41%)   21/130 (16.15%)   54/278 (19.42%) 
Dyspepsia           
# participants affected / at risk   11/148 (7.43%)   3/145 (2.07%)   7/128 (5.47%)   9/130 (6.92%)   26/278 (9.35%) 
Gastrooesophageal reflux disease           
# participants affected / at risk   11/148 (7.43%)   6/145 (4.14%)   15/128 (11.72%)   13/130 (10.00%)   39/278 (14.03%) 
Abdominal discomfort           
# participants affected / at risk   5/148 (3.38%)   2/145 (1.38%)   8/128 (6.25%)   8/130 (6.15%)   19/278 (6.83%) 
Abdominal pain           
# participants affected / at risk   5/148 (3.38%)   3/145 (2.07%)   8/128 (6.25%)   8/130 (6.15%)   20/278 (7.19%) 
Abdominal pain upper           
# participants affected / at risk   2/148 (1.35%)   2/145 (1.38%)   7/128 (5.47%)   8/130 (6.15%)   17/278 (6.12%) 
Large intestine polyp           
# participants affected / at risk   1/148 (0.68%)   0/145 (0.00%)   11/128 (8.59%)   10/130 (7.69%)   22/278 (7.91%) 
Toothache           
# participants affected / at risk   1/148 (0.68%)   3/145 (2.07%)   6/128 (4.69%)   9/130 (6.92%)   16/278 (5.76%) 
General disorders           
Injection site pruritus           
# participants affected / at risk   27/148 (18.24%)   2/145 (1.38%)   5/128 (3.91%)   9/130 (6.92%)   40/278 (14.39%) 
Injection site erythema           
# participants affected / at risk   11/148 (7.43%)   0/145 (0.00%)   7/128 (5.47%)   6/130 (4.62%)   21/278 (7.55%) 
Fatigue           
# participants affected / at risk   9/148 (6.08%)   5/145 (3.45%)   11/128 (8.59%)   12/130 (9.23%)   31/278 (11.15%) 
Injection site bruising           
# participants affected / at risk   7/148 (4.73%)   14/145 (9.66%)   7/128 (5.47%)   10/130 (7.69%)   24/278 (8.63%) 
Oedema peripheral           
# participants affected / at risk   1/148 (0.68%)   0/145 (0.00%)   6/128 (4.69%)   14/130 (10.77%)   21/278 (7.55%) 
Immune system disorders           
Seasonal allergy           
# participants affected / at risk   2/148 (1.35%)   2/145 (1.38%)   13/128 (10.16%)   5/130 (3.85%)   20/278 (7.19%) 
Infections and infestations           
Urinary tract infection           
# participants affected / at risk   15/148 (10.14%)   11/145 (7.59%)   23/128 (17.97%)   30/130 (23.08%)   63/278 (22.66%) 
Gastroenteritis viral           
# participants affected / at risk   12/148 (8.11%)   8/145 (5.52%)   18/128 (14.06%)   11/130 (8.46%)   37/278 (13.31%) 
Upper respiratory tract infection           
# participants affected / at risk   12/148 (8.11%)   25/145 (17.24%)   54/128 (42.19%)   64/130 (49.23%)   124/278 (44.60%) 
Nasopharyngitis           
# participants affected / at risk   10/148 (6.76%)   8/145 (5.52%)   34/128 (26.56%)   41/130 (31.54%)   78/278 (28.06%) 
Sinusitis           
# participants affected / at risk   7/148 (4.73%)   10/145 (6.90%)   26/128 (20.31%)   35/130 (26.92%)   66/278 (23.74%) 
Bronchitis           
# participants affected / at risk   4/148 (2.70%)   6/145 (4.14%)   18/128 (14.06%)   25/130 (19.23%)   46/278 (16.55%) 
Conjunctivitis           
# participants affected / at risk   1/148 (0.68%)   2/145 (1.38%)   6/128 (4.69%)   9/130 (6.92%)   16/278 (5.76%) 
Ear infection           
# participants affected / at risk   0/148 (0.00%)   1/145 (0.69%)   6/128 (4.69%)   7/130 (5.38%)   13/278 (4.68%) 
Gastroenteritis           
# participants affected / at risk   0/148 (0.00%)   0/145 (0.00%)   9/128 (7.03%)   6/130 (4.62%)   15/278 (5.40%) 
Herpes zoster           
# participants affected / at risk   1/148 (0.68%)   1/145 (0.69%)   7/128 (5.47%)   10/130 (7.69%)   18/278 (6.47%) 
Influenza           
# participants affected / at risk   2/148 (1.35%)   3/145 (2.07%)   11/128 (8.59%)   17/130 (13.08%)   30/278 (10.79%) 
Onychomycosis           
# participants affected / at risk   0/148 (0.00%)   0/145 (0.00%)   6/128 (4.69%)   7/130 (5.38%)   13/278 (4.68%) 
Tooth abscess           
# participants affected / at risk   3/148 (2.03%)   1/145 (0.69%)   7/128 (5.47%)   7/130 (5.38%)   17/278 (6.12%) 
Tooth infection           
# participants affected / at risk   4/148 (2.70%)   1/145 (0.69%)   10/128 (7.81%)   7/130 (5.38%)   20/278 (7.19%) 
Injury, poisoning and procedural complications           
Contusion           
# participants affected / at risk   3/148 (2.03%)   1/145 (0.69%)   12/128 (9.38%)   10/130 (7.69%)   25/278 (8.99%) 
Fall           
# participants affected / at risk   2/148 (1.35%)   2/145 (1.38%)   12/128 (9.38%)   10/130 (7.69%)   24/278 (8.63%) 
Laceration           
# participants affected / at risk   1/148 (0.68%)   1/145 (0.69%)   6/128 (4.69%)   8/130 (6.15%)   14/278 (5.04%) 
Ligament sprain           
# participants affected / at risk   1/148 (0.68%)   3/145 (2.07%)   6/128 (4.69%)   10/130 (7.69%)   17/278 (6.12%) 
Metabolism and nutrition disorders           
Diabetes mellitus           
# participants affected / at risk   0/148 (0.00%)   0/145 (0.00%)   13/128 (10.16%)   8/130 (6.15%)   21/278 (7.55%) 
Hypercholesterolaemia           
# participants affected / at risk   0/148 (0.00%)   1/145 (0.69%)   7/128 (5.47%)   6/130 (4.62%)   13/278 (4.68%) 
Musculoskeletal and connective tissue disorders           
Arthralgia           
# participants affected / at risk   7/148 (4.73%)   6/145 (4.14%)   25/128 (19.53%)   28/130 (21.54%)   58/278 (20.86%) 
Arthritis           
# participants affected / at risk   2/148 (1.35%)   3/145 (2.07%)   7/128 (5.47%)   10/130 (7.69%)   19/278 (6.83%) 
Back pain           
# participants affected / at risk   7/148 (4.73%)   6/145 (4.14%)   27/128 (21.09%)   25/130 (19.23%)   55/278 (19.78%) 
Bursitis           
# participants affected / at risk   2/148 (1.35%)   0/145 (0.00%)   5/128 (3.91%)   10/130 (7.69%)   16/278 (5.76%) 
Muscle spasms           
# participants affected / at risk   3/148 (2.03%)   3/145 (2.07%)   12/128 (9.38%)   13/130 (10.00%)   28/278 (10.07%) 
Musculoskeletal pain           
# participants affected / at risk   2/148 (1.35%)   0/145 (0.00%)   23/128 (17.97%)   15/130 (11.54%)   40/278 (14.39%) 
Myalgia           
# participants affected / at risk   5/148 (3.38%)   2/145 (1.38%)   4/128 (3.13%)   11/130 (8.46%)   19/278 (6.83%) 
Osteoarthritis           
# participants affected / at risk   1/148 (0.68%)   2/145 (1.38%)   15/128 (11.72%)   10/130 (7.69%)   26/278 (9.35%) 
Pain in extremity           
# participants affected / at risk   1/148 (0.68%)   2/145 (1.38%)   21/128 (16.41%)   22/130 (16.92%)   44/278 (15.83%) 
Tendonitis           
# participants affected / at risk   1/148 (0.68%)   0/145 (0.00%)   5/128 (3.91%)   8/130 (6.15%)   13/278 (4.68%) 
Nervous system disorders           
Headache           
# participants affected / at risk   9/148 (6.08%)   7/145 (4.83%)   15/128 (11.72%)   15/130 (11.54%)   38/278 (13.67%) 
Dizziness           
# participants affected / at risk   5/148 (3.38%)   9/145 (6.21%)   10/128 (7.81%)   10/130 (7.69%)   25/278 (8.99%) 
Psychiatric disorders           
Anxiety           
# participants affected / at risk   2/148 (1.35%)   3/145 (2.07%)   10/128 (7.81%)   6/130 (4.62%)   18/278 (6.47%) 
Depression           
# participants affected / at risk   2/148 (1.35%)   4/145 (2.76%)   10/128 (7.81%)   12/130 (9.23%)   24/278 (8.63%) 
Insomnia           
# participants affected / at risk   4/148 (2.70%)   4/145 (2.76%)   9/128 (7.03%)   11/130 (8.46%)   24/278 (8.63%) 
Renal and urinary disorders           
Nephrolithiasis           
# participants affected / at risk   2/148 (1.35%)   1/145 (0.69%)   13/128 (10.16%)   9/130 (6.92%)   23/278 (8.27%) 
Reproductive system and breast disorders           
Benign prostatic hyperplasia           
# participants affected / at risk   1/148 (0.68%)   1/145 (0.69%)   7/128 (5.47%)   6/130 (4.62%)   14/278 (5.04%) 
Respiratory, thoracic and mediastinal disorders           
Cough           
# participants affected / at risk   5/148 (3.38%)   2/145 (1.38%)   14/128 (10.94%)   14/130 (10.77%)   33/278 (11.87%) 
Epistaxis           
# participants affected / at risk   0/148 (0.00%)   0/145 (0.00%)   5/128 (3.91%)   8/130 (6.15%)   13/278 (4.68%) 
Oropharyngeal pain           
# participants affected / at risk   2/148 (1.35%)   2/145 (1.38%)   8/128 (6.25%)   12/130 (9.23%)   21/278 (7.55%) 
Sinus congestion           
# participants affected / at risk   0/148 (0.00%)   2/145 (1.38%)   7/128 (5.47%)   9/130 (6.92%)   16/278 (5.76%) 
Skin and subcutaneous tissue disorders           
Rash           
# participants affected / at risk   0/148 (0.00%)   0/145 (0.00%)   14/128 (10.94%)   8/130 (6.15%)   22/278 (7.91%) 
Vascular disorders           
Hypertension           
# participants affected / at risk   5/148 (3.38%)   4/145 (2.76%)   22/128 (17.19%)   22/130 (16.92%)   49/278 (17.63%) 
1 Term from vocabulary, MedDRA 17.0



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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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