Safety and Efficacy of Exenatide in Patients with Type 2 Diabetes Using a Thiazolidinedione or a Thiazolidinedione and Metformin

Study identifier:H8O-MC-GWCG

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

Safety and Efficacy of Exenatide in Patients with Type 2 Diabetes Using a Thiazolidinedione or a Thiazolidinedione and Metformin

Medical condition

Type 2 Diabetes Mellitus

Phase

Phase 3

Healthy volunteers

Study drug

exenatide, placebo

Sex

All

Actual Enrollment

165

Study type

Interventional

Age

18 Years +

Date

Study Start Date: 01 Jan 2008

Primary Completion Date: 01 Jul 2009

Study Completion Date: 01 Jul 2009

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2015 by AstraZeneca Pharmaceuticals

Collaborators

Eli Lilly and Company

Inclusion and exclusion criteria

Inclusion Criteria

- Diagnosed with type 2 diabetes
- If treated with a thiazolidinedione (TZD) alone, the TZD dose must have been stable for at least 120 days
- The dose of TZD must be: Rosiglitazone (≥4 mg/day) or pioglitazone
(≥30 mg/day)
- The metformin dose has been stable for at least 90 days
- Have suboptimal glycemic control as evidenced by an HbA1c between
7.1% and 10.0%, inclusive.
- Have a body mass index (BMI): 25 kg/m2 < BMI < 45 kg/m2.

Exclusion Criteria

- Have participated in this study previously or any other study using
exenatide (AC2993/LY2148568) or glucagon-like peptide-1 (GLP-1)
analogs, or have been previously treated with exenatide or GLP-1
analogs
- Have participated in an interventional medical, surgical, or pharmaceutical study (a study in which an experimental, drug, medical, or surgical treatment was given) within 30 days of screening. This criterion includes drugs that have not received regulatory approval for any indication at the time of study entry.
- Have been treated with exogenous insulin for more than 1 week within
the 2 months prior to screening
- Used drugs for weight loss (e.g., orlistat, rimonabant, sibutramine, or
similar over-the-counter medications) within 3 months prior to screening.
- Are currently treated with any of the following excluded medications:
• Sulfonylurea or meglitinide derivatives (e.g., repaglinide or nateglinide) within 3 months prior to screening
• Alpha-glucosidase inhibitor (e.g., miglitol or acarbose) within
3 months of screening
• Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g., sitagliptin or vildagliptin) within 3 months prior to screening
• Pramlintide acetate injection within 3 months prior to screening
• Drugs that directly affect gastrointestinal motility, including, but
not limited to: Metoclopramide, cisapride, and chronic macrolide
antibiotics
• Are receiving chronic (lasting longer than 2 weeks) systemic
glucocorticoid therapy (excluding topical and inhaled preparations)
or have received such therapy within the 4 weeks immediately
preceding study start

Location

Research Site

Ajax, Ontario, Canada

Location

Research Site

Cambridge, Ontario, Canada

Location

Research Site

New Westminster, British Columbia, Canada

Location

Research Site

Windsor, Ontario, Canada

Location

Research Site

Chihuahua, Chihuahua, Mexico

Location

Research Site

Celaya, Guanajuato, Mexico

Location

Research Site

Monterrey, Nuevo Leon, Mexico

Location

Research Site

Mexico City, Distrito Federal, Mexico

Arms	Assigned Interventions
Experimental: Exenatide twice daily (BID)	Drug: exenatide subcutaneous injection, 5 mcg or 10 mcg, twice a day (BID) Other Name: Byetta
Placebo Comparator: Placebo	Drug: placebo subcutaneous injection, volume equivalent to 5 mcg or 10 mcg of active drug, twice a day

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
A total of 165 patients, experiencing inadequate glycemic control using a thiazolidinedione (TZD) alone or in combination with metformin, following a 2-week placebo lead-in period, were randomly assigned in a proportion of 2:1 to add exenatide (111 patients) or placebo (54 patients) to their current therapy regimen.

Reporting Groups

	Description
Exenatide twice daily (BID)	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks
Placebo	Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks

Participant Flow: Overall Study

	Exenatide twice daily (BID)	Placebo
STARTED	111	54
COMPLETED	96	50
NOT COMPLETED	15	4
Adverse Event	4	1
Entry criteria not met	0	1
Loss of glucose control	3	0
Lost to Follow-up	2	1
Physician Decision	2	0
Protocol Violation	2	0
Subject decision	2	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Exenatide twice daily (BID)	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks
Placebo	Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks

Baseline Measures

	Exenatide twice daily (BID)	Placebo	Total
Number of Participants [units: Participants]	111	54	165
Age Categorical [units: participants]
<=18 years	0	0	0
Between 18 and 65 years	97	47	144
>=65 years	14	7	21
Age Continuous [units: years] Mean ± Standard Deviation	54.93 ± 8.27	54.12 ± 9.36	54.67 ± 8.62
Gender, Male/Female [units: participants]
Female	44	23	67
Male	67	31	98

Outcome Measures

1. Primary Outcome Measure: Change in glycosylated hemoglobin (HbA1c) [ Time Frame: baseline and 26 weeks ]

Measure Type	Primary
Measure Name	Change in glycosylated hemoglobin (HbA1c)
Measure Description	Change in HbA1c from baseline to endpoint after 26 weeks of treatment (i.e., HbA1c at endpoint minus HbA1c at baseline)
Time Frame	baseline and 26 weeks
Safety Issue?	No

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.
The number of participants was determined based on sample size calculations using parameter estimates from prior study H8O-MC-GWAP (NCT00099320), with change from baseline HbA1c as the primary efficacy measure. Primary analysis is reported for intent to treat population (ITT), last observation carried forward (LOCF).

Reporting Groups

	Description
Exenatide twice daily (BID)	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks
Placebo	Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks

Measured Values

	Exenatide twice daily (BID)	Placebo
Number of Participants Analyzed [units:participants]	110	54
Change in glycosylated hemoglobin (HbA1c) [units: Percentage] Least Squares Mean (Standard Error)	-0.84 (0.20)	-0.10 (0.23)

Statistical Analysis 1 for Change in glycosylated hemoglobin (HbA1c)

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	<0.001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Null hypothesis = Change from baseline in HbA1c is equal between the two treatment groups. Greater than 99% power to detect a difference between treatment groups of 0.88% in change in HbA1c from baseline using a 2-sided t-test at a significance level of 0.05.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No adjustments for multiplicity were made.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No adjustments were made (alpha = 0.05).

2. Secondary Outcome Measure: Percentage of patients achieving HbA1c <= 7% [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Percentage of patients achieving HbA1c <= 7%
Measure Description	Percentage of intent-to-treat (ITT) patients who had HbA1c > 7% at baseline that decreased to <= 7% at endpoint (Week 26 or early discontinuation)
Time Frame	26 weeks
Safety Issue?	No

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.
Based on primary efficacy sample size calculations. Analyses performed on ITT patient population.

Reporting Groups

	Description
Exenatide twice daily (BID)	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks
Placebo	Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks

Measured Values

	Exenatide twice daily (BID)	Placebo
Number of Participants Analyzed [units:participants]	104	52
Percentage of patients achieving HbA1c <= 7% [units: percentage of participants]	49.0	36.5

Statistical Analysis 1 for Percentage of patients achieving HbA1c <= 7%

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [CMH test]
P-Value^[4]	0.113

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Null hypothesis = Proportion of subjects with HbA1c <= 7% is equal between the two treatment groups.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No adjustment for multiplicity.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No adjustments (alpha = 0.05).

3. Secondary Outcome Measure: Percentage of patients achieving HbA1c <= 6.5% [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Percentage of patients achieving HbA1c <= 6.5%
Measure Description	Percentage of ITT patients who had achieved HbA1c <= 6.5% at endpoint (Week 26 or early discontinuation)
Time Frame	26 weeks
Safety Issue?	No

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.
Based on primary efficacy sample size calculations. Analyses performed on ITT patient population.

Reporting Groups

	Description
Exenatide twice daily (BID)	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks
Placebo	Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks

Measured Values

	Exenatide twice daily (BID)	Placebo
Number of Participants Analyzed [units:participants]	110	54
Percentage of patients achieving HbA1c <= 6.5% [units: percentage of participants]	33.6	13.0

Statistical Analysis 1 for Percentage of patients achieving HbA1c <= 6.5%

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [CMH test]
P-Value^[4]	0.004

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Null hypothesis = Proportion of subjects achieving HbA1c <= 6.5% is equal between the two treatment groups.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No adjustment for multiplicity.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No adjustments (alpha = 0.05).

4. Secondary Outcome Measure: Change in fasting serum glucose (FSG) [ Time Frame: baseline and 26 weeks ]

Measure Type	Secondary
Measure Name	Change in fasting serum glucose (FSG)
Measure Description	Change in FSG from baseline to endpoint (26 weeks)
Time Frame	baseline and 26 weeks
Safety Issue?	No

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.
Based on primary efficacy sample size calculations. Analyses performed on ITT patient population.

Reporting Groups

	Description
Exenatide twice daily (BID)	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks
Placebo	Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks

Measured Values

	Exenatide twice daily (BID)	Placebo
Number of Participants Analyzed [units:participants]	103	53
Change in fasting serum glucose (FSG) [units: mmol/L] Least Squares Mean (Standard Error)	-0.65 (0.46)	0.37 (0.52)

Statistical Analysis 1 for Change in fasting serum glucose (FSG)

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.009

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Null hypothesis = Change from baseline in FSG is equal between the two treatment groups.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No adjustment for multiplicity.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No adjustments (alpha = 0.05).

5. Secondary Outcome Measure: Change in body weight [ Time Frame: baseline and 26 weeks ]

Measure Type	Secondary
Measure Name	Change in body weight
Measure Description	Change in body weight from baseline to endpoint (26 weeks)
Time Frame	baseline and 26 weeks
Safety Issue?	No

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.
Based on primary efficacy sample size calculations. Analyses performed on ITT patient population.

Reporting Groups

	Description
Exenatide twice daily (BID)	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks
Placebo	Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks

Measured Values

	Exenatide twice daily (BID)	Placebo
Number of Participants Analyzed [units:participants]	111	54
Change in body weight [units: kg] Least Squares Mean (Standard Error)	-1.43 (0.61)	-0.75 (0.70)

Statistical Analysis 1 for Change in body weight

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.176

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Null hypothesis = Change from baseline to endpoint in body weight is equal between the two treatment groups.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No adjustment for multiplicity.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No adjustments (alpha = 0.05).

6. Secondary Outcome Measure: Change in waist circumference [ Time Frame: baseline and 26 weeks ]

Measure Type	Secondary
Measure Name	Change in waist circumference
Measure Description	Change in waist circumference from baseline to endpoint (26 weeks)
Time Frame	baseline and 26 weeks
Safety Issue?	No

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.
Based on primary efficacy sample size calculations. Analyses performed on ITT patient population.

Reporting Groups

	Description
Exenatide twice daily (BID)	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks
Placebo	Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks

Measured Values

	Exenatide twice daily (BID)	Placebo
Number of Participants Analyzed [units:participants]	109	53
Change in waist circumference [units: cm] Mean (Standard Deviation)	-2.26 (3.83)	-1.85 (3.75)

No statistical analysis provided for Change in waist circumference

7. Secondary Outcome Measure: Change in beta-cell function [ Time Frame: baseline and 26 weeks ]

Measure Type	Secondary
Measure Name	Change in beta-cell function
Measure Description	Change in homeostatic model assessment-beta cell (HOMA-B) from baseline to endpoint (Week 26) (outcome measure is presented as the ratio of endpoint HOMA-B divided by baseline HOMA-B). HOMA-B is a measure of pancreatic beta-cell function.
Time Frame	baseline and 26 weeks
Safety Issue?	No

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.
Based on primary efficacy sample size calculations. Analyses performed on ITT patient population.

Reporting Groups

	Description
Exenatide twice daily (BID)	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks
Placebo	Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks

Measured Values

	Exenatide twice daily (BID)	Placebo
Number of Participants Analyzed [units:participants]	95	49
Change in beta-cell function [units: ratio] Geometric Mean (Standard Error)	1.08 (0.12)	0.84 (0.11)

Statistical Analysis 1 for Change in beta-cell function

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.009

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Null hypothesis = Change form baseline in HOMA-B is equal between the two treatment groups.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No adjustment for multiplicity.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No adjustments (alpha = 0.05).

8. Secondary Outcome Measure: Change in insulin sensitivity. [ Time Frame: baseline and 26 weeks ]

Measure Type	Secondary
Measure Name	Change in insulin sensitivity.
Measure Description	Change in homeostatic model assessment-insulin sensitivity (HOMA-S) from baseline to endpoint (26 weeks) (outcome measure is presented as the ratio of endpoint HOMA-S divided by baseline HOMA-S).
Time Frame	baseline and 26 weeks
Safety Issue?	No

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.
Based on primary efficacy sample size calculations. Analyses performed on ITT patient population.

Reporting Groups

	Description
Exenatide twice daily (BID)	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks
Placebo	Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks

Measured Values

	Exenatide twice daily (BID)	Placebo
Number of Participants Analyzed [units:participants]	95	49
Change in insulin sensitivity. [units: ratio] Least Squares Mean (Standard Error)	1.09 (0.11)	1.07 (0.13)

Statistical Analysis 1 for Change in insulin sensitivity.

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.794

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Null hypothesis = Change from baseline in HOMA-S is equal between the two treatment groups.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No adjustment for multiplicity.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No adjustments (alpha = 0.05).

9. Secondary Outcome Measure: Number of subjects who experienced an episode of minor hypoglycemia [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Number of subjects who experienced an episode of minor hypoglycemia
Measure Description	Overall number of subjects who experienced an episode of minor hypoglycemia.
Time Frame	26 weeks
Safety Issue?	No

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.
Based on primary efficacy sample size calculations. Analyses performed on ITT patient population.

Reporting Groups

	Description
Exenatide twice daily (BID)	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks
Placebo	Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks

Measured Values

	Exenatide twice daily (BID)	Placebo
Number of Participants Analyzed [units:participants]	111	54
Number of subjects who experienced an episode of minor hypoglycemia [units: Participants]	4	1

Statistical Analysis 1 for Number of subjects who experienced an episode of minor hypoglycemia

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Fisher Exact
P-Value^[4]	1.00

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Null hypothesis = Incidence of minor hypoglycemia episodes is equal between the two treatment groups.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No adjustment for multiplicity.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No adjustments (alpha = 0.05).

10. Secondary Outcome Measure: Change in Impact of Weight on Quality of Life (IWQOL)-Lite Score [ Time Frame: baseline and 26 weeks ]

Measure Type	Secondary
Measure Name	Change in Impact of Weight on Quality of Life (IWQOL)-Lite Score
Measure Description	IWQOL-Lite analysis of change from baseline to endpoint (26 weeks). IWQOL-Lite is a 31-item questionnaire, assessing the domains of physical function, self-esteem, sexual life, public distress, and work. Response categories for each item range from 1 = “never true” to 5 = “always true.”
Time Frame	baseline and 26 weeks
Safety Issue?	No

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.
Based on primary efficacy sample size calculations. Analyses performed on ITT patient population.

Reporting Groups

	Description
Exenatide twice daily (BID)	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks
Placebo	Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks

Measured Values

	Exenatide twice daily (BID)	Placebo
Number of Participants Analyzed [units:participants]	108	53
Change in Impact of Weight on Quality of Life (IWQOL)-Lite Score [units: units on a scale] Least Squares Mean (Standard Error)
Change in Total Score	-1.56 (2.21)	0.11 (2.49)
Change in Physical Function component	-3.84 (3.06)	-1.05 (3.43)
Change in Self-Esteem component	0.20 (2.92)	-0.54 (3.28)
Change in Sexual Life component	0.12 (5.52)	5.01 (6.12)
Change in Public Distress component	-0.48 (2.61)	-0.28 (2.92)
Change in Work component	-0.91 (2.41)	0.08 (2.71)

Statistical Analysis 1 for Change in Impact of Weight on Quality of Life (IWQOL)-Lite Score

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.342

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Null hypothesis = Change from baseline in IWQOL-Lite Total Score is equal between the two treatment groups. This statistical analysis is for the Total Score only.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No adjustment for multiplicity.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No adjustments (alpha = 0.05).

11. Secondary Outcome Measure: Change in Euroqol – 5 Domain Quality of Life (EQ-5D) Score [ Time Frame: baseline and 26 weeks ]

Measure Type	Secondary
Measure Name	Change in Euroqol – 5 Domain Quality of Life (EQ-5D) Score
Measure Description	EQ-5D Score - change from baseline to endpoint (26 weeks). EQ-5D is a 5-item questionnaire used to characterize current health states. The tool and accompanying visual analog scale (VAS) assess 5 domains of quality of life, including mobility, self-care, usual activity, pain, and anxiety/depression. Weights are used to score the responses to the 5 domains, with 3 options possible in each domain: extreme problems, some/moderate problems, or no problems. Scores range from 0 to 1, with a score of 1 representing a perfect health state.
Time Frame	baseline and 26 weeks
Safety Issue?	No

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.
Based on primary efficacy sample size calculations. Analyses performed on ITT patient population.

Reporting Groups

	Description
Exenatide twice daily (BID)	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks
Placebo	Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks

Measured Values

	Exenatide twice daily (BID)	Placebo
Number of Participants Analyzed [units:participants]	108	53
Change in Euroqol – 5 Domain Quality of Life (EQ-5D) Score [units: units on a scale] Least Squares Mean (Standard Error)
Change in Health State Score	0.79 (3.54)	-2.94 (3.97)
Change in Mobility component	0.14 (0.15)	0.15 (0.17)
Change in Self Care component	0.08 (0.14)	0.03 (0.16)
Change Usual Activities component	0.17 (0.15)	0.19 (0.17)
Change in Pain/Discomfort component	0.29 (0.16)	0.23 (0.18)
Change in Anxiety/Depression component	-0.10 (0.16)	-0.26 (0.18)

Statistical Analysis 1 for Change in Euroqol – 5 Domain Quality of Life (EQ-5D) Score

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.186

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Null hypothesis = Change from baseline in EQ-5D score is equal between the two treatment groups. This statistical analysis is for the EQ-5D Health State Score only.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No adjustment for multiplicity.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No adjustments (alpha = 0.05)

Serious Adverse Events

Time Frame	Adverse events were collected from baseline to endpoint, regardless of relationship to study drug. Events were captured as actual terms and coded to MedDRA,version 12.0.
Additional Description	No text entered.

Reporting Groups

	Description
Exenatide twice daily (BID)	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks
Placebo	Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks

Serious Adverse Events

Exenatide twice daily (BID)

Placebo

Total, serious adverse events

# participants affected / at risk

1/111 (0.90%)

0/54 (0.00%)

Nervous system disorders

Ischaemic stroke¹,^†

# participants affected / at risk

1/111 (0.90%)

0/54 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 12.0

Other Adverse Events

Time Frame	Adverse events were collected from baseline to endpoint, regardless of relationship to study drug. Events were captured as actual terms and coded to MedDRA,version 12.0.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Exenatide twice daily (BID)	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks
Placebo	Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks

Other Adverse Events

Exenatide twice daily (BID)

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

22/111 (19.82%)

1/54 (1.85%)

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

13/111 (11.71%)

1/54 (1.85%)

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

9/111 (8.11%)

0/54 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 12.0

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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description:

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.

Results Point of Contact

Name/Title:	Peter Ohman, Medical Science Director
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center null

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Chief Medical Officer

Eli Lilly and Company

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Trial Results Summaries