Trial Outcomes & Findings for Effect on Weight Loss of Exenatide Versus Placebo (NCT NCT00375492)
NCT ID: NCT00375492
Last Updated: 2015-04-07
Results Overview
Change in body weight from baseline (Week 0) after 24 weeks of treatment (i.e., weight at week 24 minus weight at week 0). Body weight measured in kilograms (k).
COMPLETED
PHASE3
196 participants
Baseline, Week 24
2015-04-07
Participant Flow
One randomized patient per group discontinued before receiving study drug. These patients are not included in the "started" category below.
Participant milestones
| Measure |
Group A (Exenatide)
exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
|
Group B (Placebo)
placebo (volume equivalent to exenatide injection) twice daily for 24 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
96
|
98
|
|
Overall Study
COMPLETED
|
70
|
72
|
|
Overall Study
NOT COMPLETED
|
26
|
26
|
Reasons for withdrawal
| Measure |
Group A (Exenatide)
exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
|
Group B (Placebo)
placebo (volume equivalent to exenatide injection) twice daily for 24 weeks
|
|---|---|---|
|
Overall Study
Adverse Event
|
4
|
5
|
|
Overall Study
Entry Criteria Not Met
|
0
|
1
|
|
Overall Study
Loss of Glucose Control
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
10
|
5
|
|
Overall Study
Physician Decision
|
0
|
4
|
|
Overall Study
Protocol Violation
|
6
|
3
|
|
Overall Study
Sponsor Decision
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
6
|
6
|
Baseline Characteristics
Effect on Weight Loss of Exenatide Versus Placebo
Baseline characteristics by cohort
| Measure |
Group A (Exenatide)
n=96 Participants
exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
|
Group B (Placebo)
n=98 Participants
placebo (volume equivalent to exenatide injection) twice daily for 24 weeks
|
Total
n=194 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
78 Participants
n=99 Participants
|
82 Participants
n=107 Participants
|
160 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
18 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
34 Participants
n=206 Participants
|
|
Age, Continuous
|
54.52 years
STANDARD_DEVIATION 10.02 • n=99 Participants
|
55.08 years
STANDARD_DEVIATION 8.97 • n=107 Participants
|
54.81 years
STANDARD_DEVIATION 9.48 • n=206 Participants
|
|
Sex: Female, Male
Female
|
60 Participants
n=99 Participants
|
61 Participants
n=107 Participants
|
121 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
36 Participants
n=99 Participants
|
37 Participants
n=107 Participants
|
73 Participants
n=206 Participants
|
|
Baseline Body Weight
|
94.90 kg
STANDARD_DEVIATION 16.52 • n=99 Participants
|
96.16 kg
STANDARD_DEVIATION 16.53 • n=107 Participants
|
95.53 kg
STANDARD_DEVIATION 16.05 • n=206 Participants
|
|
Baseline Cholesterol
|
4.67 mmol/L
STANDARD_DEVIATION 1.03 • n=99 Participants
|
4.68 mmol/L
STANDARD_DEVIATION 0.90 • n=107 Participants
|
4.68 mmol/L
STANDARD_DEVIATION 0.96 • n=206 Participants
|
|
Baseline Glycosylated Hemoglobin (HbA1c)
|
7.74 percent hemoglobin
STANDARD_DEVIATION 0.87 • n=99 Participants
|
7.51 percent hemoglobin
STANDARD_DEVIATION 0.82 • n=107 Participants
|
7.62 percent hemoglobin
STANDARD_DEVIATION 0.85 • n=206 Participants
|
|
Baseline High Density Lipoprotein (HDL) Cholesterol
|
1.18 mmol/L
STANDARD_DEVIATION 0.32 • n=99 Participants
|
1.21 mmol/L
STANDARD_DEVIATION 0.31 • n=107 Participants
|
1.20 mmol/L
STANDARD_DEVIATION 0.31 • n=206 Participants
|
|
Baseline Homeostatic Model Assessment-Beta Cell (HOMA-B)
|
75.15 Percent beta-cell function
STANDARD_DEVIATION 81.20 • n=99 Participants
|
70.72 Percent beta-cell function
STANDARD_DEVIATION 53.16 • n=107 Participants
|
72.81 Percent beta-cell function
STANDARD_DEVIATION 67.65 • n=206 Participants
|
|
Baseline Homeostatic Model Assessment-Insulin Sensitivity (HOMA-S)
|
49.72 Percent insulin sensitivity
STANDARD_DEVIATION 32.12 • n=99 Participants
|
62.90 Percent insulin sensitivity
STANDARD_DEVIATION 41.07 • n=107 Participants
|
56.68 Percent insulin sensitivity
STANDARD_DEVIATION 37.57 • n=206 Participants
|
|
Baseline Low Density Lipoprotein (LDL) Cholesterol
|
2.74 mmol/L
STANDARD_DEVIATION 0.88 • n=99 Participants
|
2.78 mmol/L
STANDARD_DEVIATION 0.82 • n=107 Participants
|
2.76 mmol/L
STANDARD_DEVIATION 0.85 • n=206 Participants
|
|
Baseline Triglycerides
|
2.15 mmol/L
STANDARD_DEVIATION 0.94 • n=99 Participants
|
2.13 mmol/L
STANDARD_DEVIATION 1.00 • n=107 Participants
|
2.14 mmol/L
STANDARD_DEVIATION 0.97 • n=206 Participants
|
|
Baseline Waist Circumference
|
109.64 cm
STANDARD_DEVIATION 11.12 • n=99 Participants
|
108.85 cm
STANDARD_DEVIATION 12.10 • n=107 Participants
|
109.24 cm
STANDARD_DEVIATION 11.60 • n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 24Population: Intent to Treat population
Change in body weight from baseline (Week 0) after 24 weeks of treatment (i.e., weight at week 24 minus weight at week 0). Body weight measured in kilograms (k).
Outcome measures
| Measure |
Group A (Exenatide)
n=70 Participants
exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
|
Group B (Placebo)
n=72 Participants
placebo (volume equivalent to exenatide injection) twice daily for 24 weeks
|
|---|---|---|
|
Change From Baseline in Body Weight
|
-6.16 kg
Standard Error 0.54
|
-3.97 kg
Standard Error 0.52
|
SECONDARY outcome
Timeframe: baseline, Week 24Population: Intent to Treat population
Change in HbA1c from baseline (Week 0) after 24 weeks of treatment (i.e., HbA1c at week 24 minus HbA1c at week 0). HbA1c is measured as percent (%) of hemoglobin.
Outcome measures
| Measure |
Group A (Exenatide)
n=70 Participants
exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
|
Group B (Placebo)
n=71 Participants
placebo (volume equivalent to exenatide injection) twice daily for 24 weeks
|
|---|---|---|
|
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
|
-1.21 percent hemoglobin
Standard Error 0.09
|
-0.73 percent hemoglobin
Standard Error 0.09
|
SECONDARY outcome
Timeframe: baseline, Week 24Population: Intent to Treat population
Change in SMBG at each of 6 time points throughout a day (blood glucose measurements before and 2 hours after the start of the morning, mid-day, and evening meals); week 24 compared to week 0 (i.e., SMBG at week 24 minus SMBG at week 0). Fasting Glucose measured in millimoles per liter (mmol/L).
Outcome measures
| Measure |
Group A (Exenatide)
n=69 Participants
exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
|
Group B (Placebo)
n=72 Participants
placebo (volume equivalent to exenatide injection) twice daily for 24 weeks
|
|---|---|---|
|
Change From Baseline in 6-point Self Monitored Blood Glucose (SMBG) Profile at Week 24
2 Hours Post Morning Meal
|
-2.67 mmol/L
Standard Error 0.22
|
-1.92 mmol/L
Standard Error 0.22
|
|
Change From Baseline in 6-point Self Monitored Blood Glucose (SMBG) Profile at Week 24
Evening Pre-Meal
|
-1.57 mmol/L
Standard Error 0.19
|
-1.32 mmol/L
Standard Error 0.19
|
|
Change From Baseline in 6-point Self Monitored Blood Glucose (SMBG) Profile at Week 24
Morning Pre-Meal
|
-1.87 mmol/L
Standard Error 0.17
|
-1.20 mmol/L
Standard Error 0.17
|
|
Change From Baseline in 6-point Self Monitored Blood Glucose (SMBG) Profile at Week 24
Midday Pre-Meal
|
-1.40 mmol/L
Standard Error 0.19
|
-1.37 mmol/L
Standard Error 0.19
|
|
Change From Baseline in 6-point Self Monitored Blood Glucose (SMBG) Profile at Week 24
2 Hours Post Midday Meal
|
-2.12 mmol/L
Standard Error 0.21
|
-1.51 mmol/L
Standard Error 0.20
|
|
Change From Baseline in 6-point Self Monitored Blood Glucose (SMBG) Profile at Week 24
2 Hours Post Evening Meal
|
-3.09 mmol/L
Standard Error 0.22
|
-2.28 mmol/L
Standard Error 0.23
|
SECONDARY outcome
Timeframe: baseline, Week 24Population: Intent to Treat population
Change in waist circumference from baseline after 24 weeks of treatment (i.e., waist circumference at week 24 minus waist circumference at week 0). Waist measured in centimeters (cm).
Outcome measures
| Measure |
Group A (Exenatide)
n=69 Participants
exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
|
Group B (Placebo)
n=69 Participants
placebo (volume equivalent to exenatide injection) twice daily for 24 weeks
|
|---|---|---|
|
Change From Baseline in Waist Circumference at Week 24
|
-5.33 cm
Standard Error 0.71
|
-4.18 cm
Standard Error 0.73
|
SECONDARY outcome
Timeframe: baseline, Week 24Population: Intent to Treat population
Ratio of HOMA-B at Week 24 to HOMA-B at baseline (Week 0). HOMA-B is a computer solved model used to predict the homeostatic concentrations which arise from varying degrees beta-cell deficiency. HOMA-B allows a quantitative assessment of the contributions of deficient beta cell function to the fasting hyperglycemia. HOMA-B is measured as a percent of the normal population (normal beta cell function = 100%, which is used as a reference in the calculation). The higher the percent the better for the participant.
Outcome measures
| Measure |
Group A (Exenatide)
n=68 Participants
exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
|
Group B (Placebo)
n=76 Participants
placebo (volume equivalent to exenatide injection) twice daily for 24 weeks
|
|---|---|---|
|
Ratio of Homeostatic Model Assessment-Beta Cell (HOMA-B) at Week 24 to HOMA-B at Baseline
|
1.46 Ratio
Standard Error 0.12
|
1.29 Ratio
Standard Error 0.10
|
SECONDARY outcome
Timeframe: baseline, Week 24Population: Intent to Treat population
Ratio of HOMA-S at Week 24 to HOMA-S at baseline, week 0. HOMA-S is a computer solved model used to predict the homeostatic concentrations which arise from varying degrees of insulin sensitivity. HOMA-S allows a quantitative assessment of the contributions of insulin sensitivity to the fasting hyperglycemia. HOMA-S is measured as a percent of the normal population (normal insulin sensitivity = 100%, which is used as a reference in the calculation). The higher the percent the better for the participant.
Outcome measures
| Measure |
Group A (Exenatide)
n=68 Participants
exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
|
Group B (Placebo)
n=76 Participants
placebo (volume equivalent to exenatide injection) twice daily for 24 weeks
|
|---|---|---|
|
Ratio of Homeostatic Model Assessment-Insulin Sensitivity (HOMA-S) at Week 24 to HOMA-S at Baseline
|
1.08 Ratio
Standard Error 0.07
|
0.97 Ratio
Standard Error 0.06
|
SECONDARY outcome
Timeframe: baseline, Week 24Population: Intent to Treat population
Change in HDL cholesterol from baseline after 24 weeks of treatment (i.e., HDL cholesterol at week 24 minus HDL cholesterol at week 0). HDL measured as mmol/L.
Outcome measures
| Measure |
Group A (Exenatide)
n=81 Participants
exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
|
Group B (Placebo)
n=89 Participants
placebo (volume equivalent to exenatide injection) twice daily for 24 weeks
|
|---|---|---|
|
Change From Baseline in High Density Lipoprotein (HDL) Cholesterol at Week 24
|
0.02 mmol/L
Standard Error 0.02
|
0.02 mmol/L
Standard Error 0.02
|
SECONDARY outcome
Timeframe: baseline, Week 24Population: Intent to Treat population
Change in LDL cholesterol from baseline (Week 0) after 24 weeks of treatment (ie., LDL cholesterol at week 24 minus LDL cholesterol at week 0). LDL cholesterol measured in mmol/L
Outcome measures
| Measure |
Group A (Exenatide)
n=81 Participants
exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
|
Group B (Placebo)
n=89 Participants
placebo (volume equivalent to exenatide injection) twice daily for 24 weeks
|
|---|---|---|
|
Change From Baseline in Low Density Lipoprotein (LDL) Cholesterol at Week 24
|
-0.06 mmol/L
Standard Error 0.08
|
-0.04 mmol/L
Standard Error 0.07
|
SECONDARY outcome
Timeframe: baseline, week 24Population: Intent to Treat population
Change in total cholesterol from baseline after 24 weeks of treatment (i.e., total cholesterol at week 24 minus total cholesterol at week 0). Total cholesterol measured in mmol/L.
Outcome measures
| Measure |
Group A (Exenatide)
n=81 Participants
exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
|
Group B (Placebo)
n=89 Participants
placebo (volume equivalent to exenatide injection) twice daily for 24 weeks
|
|---|---|---|
|
Change From Baseline in Total Cholesterol at Week 24
|
-0.16 mmol/L
Standard Error 0.10
|
-0.03 mmol/L
Standard Error 0.10
|
SECONDARY outcome
Timeframe: baseline, Week 24Population: Intent to Treat population
Ratio of triglyceride levels at Week 24 to triglyceride levels at baseline, Week 0 (ie., triglycerides at Week 24 divided by triglycerides at baseline, Week 0). Triglycerides measured in mmol/L.
Outcome measures
| Measure |
Group A (Exenatide)
n=81 Participants
exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
|
Group B (Placebo)
n=89 Participants
placebo (volume equivalent to exenatide injection) twice daily for 24 weeks
|
|---|---|---|
|
Ratio of Triglycerides at Week 24 to Triglycerides at Baseline
|
0.83 Ratio
Standard Error 0.04
|
0.92 Ratio
Standard Error 0.04
|
SECONDARY outcome
Timeframe: Baseline to 24 weeksPopulation: Intent to Treat population
Number of participants experiencing one or more events of hypoglycemia at any point in the study
Outcome measures
| Measure |
Group A (Exenatide)
n=96 Participants
exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
|
Group B (Placebo)
n=98 Participants
placebo (volume equivalent to exenatide injection) twice daily for 24 weeks
|
|---|---|---|
|
Number of Participants With Hypoglycemic Events During the Study
|
33 participants
|
30 participants
|
SECONDARY outcome
Timeframe: 24 weeksPopulation: Intent to Treat population
Overall rate of hypoglycemia, adjusted for 1 year (ie., events of hypoglycemia per participant per year).
Outcome measures
| Measure |
Group A (Exenatide)
n=96 Participants
exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
|
Group B (Placebo)
n=98 Participants
placebo (volume equivalent to exenatide injection) twice daily for 24 weeks
|
|---|---|---|
|
Rate of Hypoglycemic Events
|
7.14 events per patient per year
Standard Error 1.45
|
4.58 events per patient per year
Standard Error 1.43
|
Adverse Events
Group A (Exenatide)
Group B (Placebo)
Serious adverse events
| Measure |
Group A (Exenatide)
exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
|
Group B (Placebo)
placebo (volume equivalent to exenatide injection) twice daily for 24 weeks
|
|---|---|---|
|
Gastrointestinal disorders
Gastroenteritis bacterial
|
1.0%
1/96
|
0.00%
0/98
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/96
|
1.0%
1/98
|
|
Renal and urinary disorders
Nephrolithiasis
|
1.0%
1/96
|
0.00%
0/98
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/96
|
1.0%
1/98
|
Other adverse events
| Measure |
Group A (Exenatide)
exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
|
Group B (Placebo)
placebo (volume equivalent to exenatide injection) twice daily for 24 weeks
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
44.8%
43/96
|
19.4%
19/98
|
|
Gastrointestinal disorders
Diarrhea
|
18.8%
18/96
|
21.4%
21/98
|
|
Infections and infestations
Upper respiratory tract infection
|
17.7%
17/96
|
17.3%
17/98
|
|
Gastrointestinal disorders
Vomiting
|
21.9%
21/96
|
9.2%
9/98
|
|
Nervous system disorders
Headache
|
11.5%
11/96
|
9.2%
9/98
|
|
Gastrointestinal disorders
Constipation
|
9.4%
9/96
|
10.2%
10/98
|
|
General disorders
Injection site bruising
|
5.2%
5/96
|
14.3%
14/98
|
|
Infections and infestations
Nasopharyngitis
|
11.5%
11/96
|
6.1%
6/98
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
4.2%
4/96
|
8.2%
8/98
|
|
Metabolism and nutrition disorders
Decreased appetite
|
6.2%
6/96
|
6.1%
6/98
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
7.3%
7/96
|
5.1%
5/98
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.2%
5/96
|
6.1%
6/98
|
|
Injury, poisoning and procedural complications
Contusion
|
6.2%
6/96
|
4.1%
4/98
|
|
Nervous system disorders
Dizziness
|
5.2%
5/96
|
5.1%
5/98
|
|
Infections and infestations
Urinary tract infection
|
3.1%
3/96
|
7.1%
7/98
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.2%
5/96
|
2.0%
2/98
|
|
Gastrointestinal disorders
Dysgeusia
|
5.2%
5/96
|
1.0%
1/98
|
|
General disorders
Injection site pruritus
|
6.2%
6/96
|
0.00%
0/98
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
1.0%
1/96
|
5.1%
5/98
|
|
General disorders
Injection site erythema
|
5.2%
5/96
|
0.00%
0/98
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
5.2%
5/96
|
0.00%
0/98
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER