Trial Outcomes & Findings for Safety and Efficacy of Exenatide in Patients With Type 2 Diabetes Using a Thiazolidinedione or a Thiazolidinedione and Metformin (NCT NCT00603239)

NCT ID: NCT00603239

Last Updated: 2015-04-07

Results Overview

Change in HbA1c from baseline to endpoint after 26 weeks of treatment (i.e., HbA1c at endpoint minus HbA1c at baseline)

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 165 participants
• Primary outcome timeframe: baseline and 26 weeks
• Results posted on: 2015-04-07

Participant Flow

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.

Participant milestones

Measure	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
Overall Study STARTED	111	54
Overall Study COMPLETED	96	50
Overall Study NOT COMPLETED	15	4

Reasons for withdrawal

Measure	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
Overall Study Adverse Event	4	1
Overall Study Entry criteria not met	0	1
Overall Study Loss of glucose control	3	0
Overall Study Lost to Follow-up	2	1
Overall Study Physician Decision	2	0
Overall Study Protocol Violation	2	0
Overall Study Subject decision	2	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Exenatide Twice Daily (BID) n=111 Participants Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks	Placebo n=54 Participants Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks	Total n=165 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	97 Participants n=93 Participants	47 Participants n=4 Participants	144 Participants n=27 Participants
Age, Categorical >=65 years	14 Participants n=93 Participants	7 Participants n=4 Participants	21 Participants n=27 Participants
Age, Continuous	54.93 years STANDARD_DEVIATION 8.27 • n=93 Participants	54.12 years STANDARD_DEVIATION 9.36 • n=4 Participants	54.67 years STANDARD_DEVIATION 8.62 • n=27 Participants
Sex: Female, Male Female	44 Participants n=93 Participants	23 Participants n=4 Participants	67 Participants n=27 Participants
Sex: Female, Male Male	67 Participants n=93 Participants	31 Participants n=4 Participants	98 Participants n=27 Participants

PRIMARY outcome

Timeframe: baseline and 26 weeks

Population: 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).

Change in HbA1c from baseline to endpoint after 26 weeks of treatment (i.e., HbA1c at endpoint minus HbA1c at baseline)

Outcome measures

Measure	Exenatide Twice Daily (BID) n=110 Participants Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks	Placebo n=54 Participants Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks
Change in Glycosylated Hemoglobin (HbA1c)	-0.84 Percentage Standard Error 0.20	-0.10 Percentage Standard Error 0.23

SECONDARY outcome

Timeframe: 26 weeks

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

Percentage of intent-to-treat (ITT) patients who had HbA1c > 7% at baseline that decreased to <= 7% at endpoint (Week 26 or early discontinuation)

Outcome measures

Measure	Exenatide Twice Daily (BID) n=104 Participants Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks	Placebo n=52 Participants Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks
Percentage of Patients Achieving HbA1c <= 7%	49.0 percentage of participants	36.5 percentage of participants

SECONDARY outcome

Timeframe: 26 weeks

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

Percentage of ITT patients who had achieved HbA1c <= 6.5% at endpoint (Week 26 or early discontinuation)

Outcome measures

Measure	Exenatide Twice Daily (BID) n=110 Participants Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks	Placebo n=54 Participants Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks
Percentage of Patients Achieving HbA1c <= 6.5%	33.6 percentage of participants	13.0 percentage of participants

SECONDARY outcome

Timeframe: baseline and 26 weeks

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

Change in FSG from baseline to endpoint (26 weeks)

Outcome measures

Measure	Exenatide Twice Daily (BID) n=103 Participants Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks	Placebo n=53 Participants Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks
Change in Fasting Serum Glucose (FSG)	-0.65 mmol/L Standard Error 0.46	0.37 mmol/L Standard Error 0.52

SECONDARY outcome

Timeframe: baseline and 26 weeks

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

Change in body weight from baseline to endpoint (26 weeks)

Outcome measures

Measure	Exenatide Twice Daily (BID) n=111 Participants Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks	Placebo n=54 Participants Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks
Change in Body Weight	-1.43 kg Standard Error 0.61	-0.75 kg Standard Error 0.70

SECONDARY outcome

Timeframe: baseline and 26 weeks

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

Change in waist circumference from baseline to endpoint (26 weeks)

Outcome measures

Measure	Exenatide Twice Daily (BID) n=109 Participants Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks	Placebo n=53 Participants Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks
Change in Waist Circumference	-2.26 cm Standard Deviation 3.83	-1.85 cm Standard Deviation 3.75

SECONDARY outcome

Timeframe: baseline and 26 weeks

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

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.

Outcome measures

Measure	Exenatide Twice Daily (BID) n=95 Participants Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks	Placebo n=49 Participants Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks
Change in Beta-cell Function	1.08 ratio Standard Error 0.12	0.84 ratio Standard Error 0.11

SECONDARY outcome

Timeframe: baseline and 26 weeks

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

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).

Outcome measures

Measure	Exenatide Twice Daily (BID) n=95 Participants Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks	Placebo n=49 Participants Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks
Change in Insulin Sensitivity.	1.09 ratio Standard Error 0.11	1.07 ratio Standard Error 0.13

SECONDARY outcome

Timeframe: 26 weeks

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

Overall number of subjects who experienced an episode of minor hypoglycemia.

Outcome measures

Measure	Exenatide Twice Daily (BID) n=111 Participants Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks	Placebo n=54 Participants Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks
Number of Subjects Who Experienced an Episode of Minor Hypoglycemia	4 Participants	1 Participants

SECONDARY outcome

Timeframe: baseline and 26 weeks

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

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."

Outcome measures

Measure	Exenatide Twice Daily (BID) n=108 Participants Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks	Placebo n=53 Participants Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks
Change in Impact of Weight on Quality of Life (IWQOL)-Lite Score Change in Physical Function component	-3.84 units on a scale Standard Error 3.06	-1.05 units on a scale Standard Error 3.43
Change in Impact of Weight on Quality of Life (IWQOL)-Lite Score Change in Work component	-0.91 units on a scale Standard Error 2.41	0.08 units on a scale Standard Error 2.71
Change in Impact of Weight on Quality of Life (IWQOL)-Lite Score Change in Total Score	-1.56 units on a scale Standard Error 2.21	0.11 units on a scale Standard Error 2.49
Change in Impact of Weight on Quality of Life (IWQOL)-Lite Score Change in Self-Esteem component	0.20 units on a scale Standard Error 2.92	-0.54 units on a scale Standard Error 3.28
Change in Impact of Weight on Quality of Life (IWQOL)-Lite Score Change in Sexual Life component	0.12 units on a scale Standard Error 5.52	5.01 units on a scale Standard Error 6.12
Change in Impact of Weight on Quality of Life (IWQOL)-Lite Score Change in Public Distress component	-0.48 units on a scale Standard Error 2.61	-0.28 units on a scale Standard Error 2.92

SECONDARY outcome

Timeframe: baseline and 26 weeks

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

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.

Outcome measures

Measure	Exenatide Twice Daily (BID) n=108 Participants Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks	Placebo n=53 Participants Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks
Change in Euroqol - 5 Domain Quality of Life (EQ-5D) Score Change in Mobility component	0.14 units on a scale Standard Error 0.15	0.15 units on a scale Standard Error 0.17
Change in Euroqol - 5 Domain Quality of Life (EQ-5D) Score Change in Health State Score	0.79 units on a scale Standard Error 3.54	-2.94 units on a scale Standard Error 3.97
Change in Euroqol - 5 Domain Quality of Life (EQ-5D) Score Change in Self Care component	0.08 units on a scale Standard Error 0.14	0.03 units on a scale Standard Error 0.16
Change in Euroqol - 5 Domain Quality of Life (EQ-5D) Score Change Usual Activities component	0.17 units on a scale Standard Error 0.15	0.19 units on a scale Standard Error 0.17
Change in Euroqol - 5 Domain Quality of Life (EQ-5D) Score Change in Pain/Discomfort component	0.29 units on a scale Standard Error 0.16	0.23 units on a scale Standard Error 0.18
Change in Euroqol - 5 Domain Quality of Life (EQ-5D) Score Change in Anxiety/Depression component	-0.10 units on a scale Standard Error 0.16	-0.26 units on a scale Standard Error 0.18

Adverse Events

Exenatide Twice Daily (BID)

Serious events: 1 serious events

Other events: 22 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Exenatide Twice Daily (BID) n=111 participants at risk Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks	Placebo n=54 participants at risk Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks
Nervous system disorders Ischaemic stroke	0.90% 1/111 • Number of events 1 • 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.	0.00% 0/54 • 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.

Other adverse events

Measure	Exenatide Twice Daily (BID) n=111 participants at risk Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks	Placebo n=54 participants at risk Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks
Gastrointestinal disorders Nausea	11.7% 13/111 • 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.	1.9% 1/54 • 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.
Gastrointestinal disorders Vomiting	8.1% 9/111 • 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.	0.00% 0/54 • 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 Information

Peter Ohman, Medical Science Director

AstraZeneca

Email: ClinicalTrialTransparency@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60