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

History of Changes

Results First Received: February 14, 2012

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition:	Type 2 Diabetes Mellitus
Interventions:	Drug: exenatide, long acting release Drug: exenatide

Participant Flow

Hide Participant Flow

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

Hide Baseline Characteristics

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 ]

Show Outcome Measure 1

2. Secondary:

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

Show Outcome Measure 2

3. Secondary:

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

Show Outcome Measure 3

4. Secondary:

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

Show Outcome Measure 4

5. Secondary:

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

Show Outcome Measure 5

6. Secondary:

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

Show Outcome Measure 6

7. Secondary:

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

Show Outcome Measure 7

8. Secondary:

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

Show Outcome Measure 8

9. Secondary:

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

Show Outcome Measure 9

10. Secondary:

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

Show Outcome Measure 10

11. Secondary:

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

Show Outcome Measure 11

12. Secondary:

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

Show Outcome Measure 12

13. Secondary:

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

Hide Outcome Measure 13

Measure Type	Secondary
Measure Title	Change in Fasting Plasma Glucose From Baseline to Week 364
Measure Description	Change in fasting plasma glucose from baseline (Day -3) to Week 364.
Time Frame	Day -3, Week 364

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.
7-Year Completer Population. Missing data up to Week 364 were imputed using the LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.

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.
All Treatment	No text entered.

Measured Values

	Exenatide Once Weekly -> Exenatide Once Weekly	Exenatide Twice Daily -> Exenatide Once Weekly	All Treatment
Participants Analyzed [Units: Participants]	58	64	122
Change in Fasting Plasma Glucose From Baseline to Week 364 [Units: mg/dL] Least Squares Mean (95% Confidence Interval)	-18.3 (-30.8 to -5.7)	-27.7 (-39.0 to -16.4)	-23.6 (-33.0 to -14.2)

No statistical analysis provided for Change in Fasting Plasma Glucose From Baseline to Week 364

14. Secondary:

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

Show Outcome Measure 14

15. Secondary:

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

Show Outcome Measure 15

16. Secondary:

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

Show Outcome Measure 16

17. Secondary:

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

Show Outcome Measure 17

18. Secondary:

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

Show Outcome Measure 18

19. Secondary:

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

Show Outcome Measure 19

20. Secondary:

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

Show Outcome Measure 20

21. Secondary:

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

Show Outcome Measure 21

22. Secondary:

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

Show Outcome Measure 22

23. Secondary:

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

Show Outcome Measure 23

24. Secondary:

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

Show Outcome Measure 24

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.

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.

Serious Adverse Events

Show Serious Adverse Events

Other Adverse Events

Show Other Adverse Events

Limitations and Caveats

Hide Limitations and Caveats

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
No text entered.

More Information

Show More Information

To Top