Trial Outcomes & Findings for A Pilot Study of Effects of Exenatide on Body Weight in Non-Diabetic, Obese Patients (NCT NCT00500370)

NCT ID: NCT00500370

Last Updated: 2015-04-07

Results Overview

Change in body weight from baseline after 24 weeks of treatment (i.e., body weight at week 24 minus body weight at week 0)

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 163 participants
• Primary outcome timeframe: 24 weeks
• Results posted on: 2015-04-07

Participant Flow

Subject recruitment occurred between July 2007 and August 2007 at medical clinics in the United States.

Prior to randomization, subjects participated in a 1-week, single-blind placebo lead-in period.

Participant milestones

Measure	Group A (Exenatide) exenatide 5mcg twice daily for 4 weeks plus lifestyle modification plan (LMP), followed by exenatide 10mcg twice daily for 20 weeks plus LMP	Group B (Placebo) placebo (volume equivalent to exenatide injection) twice daily for 24 weeks plus LMP
Overall Study STARTED	80	83
Overall Study Treatment Start-Baseline (Week 0)	73	79
Overall Study Treatment Complete (Week 24)	48	54
Overall Study COMPLETED	47	49
Overall Study NOT COMPLETED	33	34

Reasons for withdrawal

Measure	Group A (Exenatide) exenatide 5mcg twice daily for 4 weeks plus lifestyle modification plan (LMP), followed by exenatide 10mcg twice daily for 20 weeks plus LMP	Group B (Placebo) placebo (volume equivalent to exenatide injection) twice daily for 24 weeks plus LMP
Overall Study Adverse Event	9	3
Overall Study Lost to Follow-up	10	10
Overall Study Protocol Violation	2	4
Overall Study Sponsor Decision	2	0
Overall Study Subject Decision	10	17

Baseline Characteristics

A Pilot Study of Effects of Exenatide on Body Weight in Non-Diabetic, Obese Patients

Baseline characteristics by cohort

Measure	Group A (Exenatide) n=73 Participants exenatide 5mcg twice daily for 4 weeks plus lifestyle modification plan (LMP), followed by exenatide 10mcg twice daily for 20 weeks plus LMP	Group B (Placebo) n=79 Participants placebo (volume equivalent to exenatide injection) twice daily for 24 weeks plus LMP	Total n=152 Participants Total of all reporting groups
Age, Continuous	47.01 years STANDARD_DEVIATION 10.95 • n=5 Participants	45.15 years STANDARD_DEVIATION 12.74 • n=7 Participants	46.04 years STANDARD_DEVIATION 11.91 • n=5 Participants
Sex: Female, Male Female	58 Participants n=5 Participants	67 Participants n=7 Participants	125 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	12 Participants n=7 Participants	27 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks

Population: Intent to Treat population

Change in body weight from baseline after 24 weeks of treatment (i.e., body weight at week 24 minus body weight at week 0)

Outcome measures

Measure	Group A (Exenatide) n=73 Participants exenatide 5mcg twice daily for 4 weeks plus lifestyle modification plan (LMP), followed by exenatide 10mcg twice daily for 20 weeks plus LMP	Group B (Placebo) n=78 Participants placebo (volume equivalent to exenatide injection) twice daily for 24 weeks plus LMP
Change in Body Weight Baseline (Week 0)	109.48 kg Standard Error 2.70	107.64 kg Standard Error 2.61
Change in Body Weight Change at Endpoint (Week 24)	-5.06 kg Standard Error 0.49	-1.61 kg Standard Error 0.47

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent to Treat population

Change in BMI from baseline after 24 weeks of treatment (i.e., BMI at week 24 minus BMI at week 0)

Outcome measures

Measure	Group A (Exenatide) n=73 Participants exenatide 5mcg twice daily for 4 weeks plus lifestyle modification plan (LMP), followed by exenatide 10mcg twice daily for 20 weeks plus LMP	Group B (Placebo) n=78 Participants placebo (volume equivalent to exenatide injection) twice daily for 24 weeks plus LMP
Change in Body Mass Index (BMI) Baseline (Week 0)	39.64 kg/m^2 Standard Error 0.82	39.39 kg/m^2 Standard Error 0.79
Change in Body Mass Index (BMI) Change at Endpoint (Week 24)	-1.83 kg/m^2 Standard Error 0.18	-0.58 kg/m^2 Standard Error 0.17

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent to Treat population

Waist-to-hip ratio at week 24 compared to waist-to-hip ratio at week 0 (i.e., waist-to-hip ratio at week 24 minus waist-to-hip ratio at week 0). Waist-to-hip ratio equals waist circumference at given time point divided by hip circumference at given timepoint.

Outcome measures

Measure	Group A (Exenatide) n=69 Participants exenatide 5mcg twice daily for 4 weeks plus lifestyle modification plan (LMP), followed by exenatide 10mcg twice daily for 20 weeks plus LMP	Group B (Placebo) n=70 Participants placebo (volume equivalent to exenatide injection) twice daily for 24 weeks plus LMP
Change in Waist-to-hip Ratio Baseline (Week 0)	0.90 Ratio Standard Error 0.01	0.90 Ratio Standard Error 0.01
Change in Waist-to-hip Ratio Change at Endpoint (Week 24)	-0.001 Ratio Standard Error 0.01	0.002 Ratio Standard Error 0.01

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent to Treat population; Last Observation Carried Forward

Percentage of exenatide and placebo treated patients experiencing >=5% weight loss after 24 weeks of treatment (i.e., [weight at week 0 minus weight at week 24] divided by weight at week 0 times 100% >=5%)

Outcome measures

Measure	Group A (Exenatide) n=73 Participants exenatide 5mcg twice daily for 4 weeks plus lifestyle modification plan (LMP), followed by exenatide 10mcg twice daily for 20 weeks plus LMP	Group B (Placebo) n=79 Participants placebo (volume equivalent to exenatide injection) twice daily for 24 weeks plus LMP
Percentage of Patients Experiencing >=5% Weight Loss	31.5 percentage of patients	16.5 percentage of patients

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent to Treat population; Last Observation Carried Forward

Change in total cholesterol from baseline after 24 weeks of treatment (i.e., total cholesterol at week 24 minus total cholesterol at week 0)

Outcome measures

Measure	Group A (Exenatide) n=67 Participants exenatide 5mcg twice daily for 4 weeks plus lifestyle modification plan (LMP), followed by exenatide 10mcg twice daily for 20 weeks plus LMP	Group B (Placebo) n=70 Participants placebo (volume equivalent to exenatide injection) twice daily for 24 weeks plus LMP
Change in Total Cholesterol Baseline (Week 0)	4.87 mmol/L Standard Error 0.11	4.88 mmol/L Standard Error 0.10
Change in Total Cholesterol Change at Endpoint (Week 24)	0.19 mmol/L Standard Error 0.11	0.33 mmol/L Standard Error 0.11

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent to Treat population; Last Observation Carried Forward

Change in HDL cholesterol from baseline after 24 weeks of treatment (i.e., HDL cholesterol at week 24 minus HDL cholesterol at week 0)

Outcome measures

Measure	Group A (Exenatide) n=67 Participants exenatide 5mcg twice daily for 4 weeks plus lifestyle modification plan (LMP), followed by exenatide 10mcg twice daily for 20 weeks plus LMP	Group B (Placebo) n=70 Participants placebo (volume equivalent to exenatide injection) twice daily for 24 weeks plus LMP
Change in High Density Lipoprotein (HDL) Cholesterol Baseline (Week 0)	1.27 mmol/L Standard Error 0.04	1.36 mmol/L Standard Error 0.04
Change in High Density Lipoprotein (HDL) Cholesterol Change at Endpoint (Week 24)	0.004 mmol/L Standard Error 0.03	0.06 mmol/L Standard Error 0.03

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent to Treat population; Last Observation Carried Forward

Ratio of triglycerides at week 24 compared to triglycerides at week 0 (i.e., triglycerides at week 24 divided by triglycerides at week 0)

Outcome measures

Measure	Group A (Exenatide) n=67 Participants exenatide 5mcg twice daily for 4 weeks plus lifestyle modification plan (LMP), followed by exenatide 10mcg twice daily for 20 weeks plus LMP	Group B (Placebo) n=70 Participants placebo (volume equivalent to exenatide injection) twice daily for 24 weeks plus LMP
Ratio of Endpoint (LOCF) to Baseline for Fasting Triglycerides (Logarithmically Transformed)	0.99 Ratio Standard Error 0.06	0.96 Ratio Standard Error 0.06

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent to Treat population; Last Observation Carried Forward

Change in LDL cholesterol from baseline following 24 weeks of treatment (i.e., LDL cholesterol at week 24 minus LDL cholesterol at week 0)

Outcome measures

Measure	Group A (Exenatide) n=67 Participants exenatide 5mcg twice daily for 4 weeks plus lifestyle modification plan (LMP), followed by exenatide 10mcg twice daily for 20 weeks plus LMP	Group B (Placebo) n=67 Participants placebo (volume equivalent to exenatide injection) twice daily for 24 weeks plus LMP
Change in Low Density Lipoprotein (LDL) Cholesterol Baseline (Week 0)	2.86 mmol/L Standard Error 0.10	2.79 mmol/L Standard Error 0.10
Change in Low Density Lipoprotein (LDL) Cholesterol Change at Endpoint (Week 24)	0.20 mmol/L Standard Error 0.09	0.34 mmol/L Standard Error 0.09

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent to Treat population

Change in fasting serum glucose from baseline following 24 weeks of treatment (i.e., fasting serum glucose at week 24 minus fasting serum glucose at week 0)

Outcome measures

Measure	Group A (Exenatide) n=67 Participants exenatide 5mcg twice daily for 4 weeks plus lifestyle modification plan (LMP), followed by exenatide 10mcg twice daily for 20 weeks plus LMP	Group B (Placebo) n=64 Participants placebo (volume equivalent to exenatide injection) twice daily for 24 weeks plus LMP
Change in Fasting Serum Glucose Baseline (Week 0)	5.37 mmol/L Standard Error 0.07	5.37 mmol/L Standard Error 0.07
Change in Fasting Serum Glucose Change at Endpoint (Week 24)	0.000 mmol/L Standard Error 0.10	-0.02 mmol/L Standard Error 0.10

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent to Treat population; Last Observation Carried Forward

Change in serum glucose AUC following OGTT (week 24 compared to week 0) (i.e., serum glucose AUC at week 24 minus serum glucose AUC at week 0)

Outcome measures

Measure	Group A (Exenatide) n=62 Participants exenatide 5mcg twice daily for 4 weeks plus lifestyle modification plan (LMP), followed by exenatide 10mcg twice daily for 20 weeks plus LMP	Group B (Placebo) n=62 Participants placebo (volume equivalent to exenatide injection) twice daily for 24 weeks plus LMP
Change in Serum Glucose AUC Levels Following Oral Glucose Tolerance Test (OGTT) Baseline (Week 0)	15.73 (mmol*hr)/L Standard Error 0.42	15.19 (mmol*hr)/L Standard Error 0.42
Change in Serum Glucose AUC Levels Following Oral Glucose Tolerance Test (OGTT) Change at Endpoint (Week 24)	-0.47 (mmol*hr)/L Standard Error 0.37	-0.01 (mmol*hr)/L Standard Error 0.37

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent to Treat population; Last Observation Carried Forward

Ratio of HOMA-B at week 24 to HOMA-B at week 0 (i.e., HOMA-B at week 24 divided by HOMA-B at week 0). HOMA-B is a measure of beta cell function.

Outcome measures

Measure	Group A (Exenatide) n=57 Participants exenatide 5mcg twice daily for 4 weeks plus lifestyle modification plan (LMP), followed by exenatide 10mcg twice daily for 20 weeks plus LMP	Group B (Placebo) n=54 Participants placebo (volume equivalent to exenatide injection) twice daily for 24 weeks plus LMP
Ratio of Endpoint (LOCF) to Baseline for Homeostatic Model Assessment-Beta Cell (HOMA-B) (Logarithmically Transformed)	1.06 Ratio Standard Error 0.07	1.08 Ratio Standard Error 0.07

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent to Treat population; Last Observation Carried Forward

Ratio of HOMA-S at week 24 to HOMA-S at week 0 (i.e., HOMA-S at week 24 divided by HOMA-S at week 0). HOMA-S is a measure of insulin sensitivity.

Outcome measures

Measure	Group A (Exenatide) n=57 Participants exenatide 5mcg twice daily for 4 weeks plus lifestyle modification plan (LMP), followed by exenatide 10mcg twice daily for 20 weeks plus LMP	Group B (Placebo) n=54 Participants placebo (volume equivalent to exenatide injection) twice daily for 24 weeks plus LMP
Ratio of Endpoint (LOCF) to Baseline for Homeostatic Model Assessment-Insulin Sensitivity (HOMA-S) (Logarithmically Transformed)	0.92 Ratio Standard Error 0.08	0.91 Ratio Standard Error 0.08

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent to Treat population

Number of patients in each treatment group that demonstrate overt signs of diabetes mellitus diagnosis by week 24

Outcome measures

Measure	Group A (Exenatide) n=65 Participants exenatide 5mcg twice daily for 4 weeks plus lifestyle modification plan (LMP), followed by exenatide 10mcg twice daily for 20 weeks plus LMP	Group B (Placebo) n=65 Participants placebo (volume equivalent to exenatide injection) twice daily for 24 weeks plus LMP
Incidence of Patients That Demonstrate Overt Signs of Diabetes Mellitus Diagnosis	3 Participants	2 Participants

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent to Treat population

Number of patients in each treatment group that demonstrate normalization of IFG and/or IGT by week 24

Outcome measures

Measure	Group A (Exenatide) n=17 Participants exenatide 5mcg twice daily for 4 weeks plus lifestyle modification plan (LMP), followed by exenatide 10mcg twice daily for 20 weeks plus LMP	Group B (Placebo) n=16 Participants placebo (volume equivalent to exenatide injection) twice daily for 24 weeks plus LMP
Incidence of Patients That Demonstrate Normalization of Impaired Fasting Glucose (IFG) and/or Impaired Glucose Tolerance (IGT)	13 Participants	9 Participants

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent to Treat population

Change in hsCRP levels from baseline following 24 weeks of treatment (i.e., hsCRP at week 24 minus hsCRP at week 0)

Outcome measures

Measure	Group A (Exenatide) n=68 Participants exenatide 5mcg twice daily for 4 weeks plus lifestyle modification plan (LMP), followed by exenatide 10mcg twice daily for 20 weeks plus LMP	Group B (Placebo) n=70 Participants placebo (volume equivalent to exenatide injection) twice daily for 24 weeks plus LMP
Change in High Sensitivity C-reactive Protein (hsCRP) Baseline (Week 0)	8.61 pmol/L Standard Error 0.91	8.03 pmol/L Standard Error 0.90
Change in High Sensitivity C-reactive Protein (hsCRP) Change at Endpoint (Week 24)	-1.31 pmol/L Standard Error 0.85	-0.44 pmol/L Standard Error 0.83

SECONDARY outcome

Timeframe: 24 weeks

Population: Intent to Treat population

Change in HbA1c from baseline following 24 weeks of treatment (i.e., HbA1c at week 24 minus HbA1c at week 0)

Outcome measures

Measure	Group A (Exenatide) n=67 Participants exenatide 5mcg twice daily for 4 weeks plus lifestyle modification plan (LMP), followed by exenatide 10mcg twice daily for 20 weeks plus LMP	Group B (Placebo) n=70 Participants placebo (volume equivalent to exenatide injection) twice daily for 24 weeks plus LMP
Change in Glycosylated Hemoglobin (HbA1c) Baseline (Week 0)	5.61 percent Standard Error 0.04	5.58 percent Standard Error 0.04
Change in Glycosylated Hemoglobin (HbA1c) Change at Endpoint (Week 24)	-0.003 percent Standard Error 0.04	0.09 percent Standard Error 0.04

Adverse Events

Group A (Exenatide)

Serious events: 0 serious events

Other events: 60 other events

Deaths: 0 deaths

Group B (Placebo)

Serious events: 0 serious events

Other events: 53 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Group A (Exenatide) n=73 participants at risk exenatide 5mcg twice daily for 4 weeks plus lifestyle modification plan (LMP), followed by exenatide 10mcg twice daily for 20 weeks plus LMP	Group B (Placebo) n=79 participants at risk placebo (volume equivalent to exenatide injection) twice daily for 24 weeks plus LMP
Gastrointestinal disorders Nausea	24.7% 18/73	3.8% 3/79
Gastrointestinal disorders Diarrhea	13.7% 10/73	2.5% 2/79
Nervous system disorders Headache	9.6% 7/73	6.3% 5/79
Infections and infestations Sinusitis	9.6% 7/73	8.9% 7/79
Gastrointestinal disorders Vomiting	8.2% 6/73	1.3% 1/79
General disorders Pain	6.8% 5/73	0.00% 0/79
Respiratory, thoracic and mediastinal disorders Cough	5.5% 4/73	2.5% 2/79
Nervous system disorders Dizziness	5.5% 4/73	0.00% 0/79
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	5.5% 4/73	0.00% 0/79
Infections and infestations Nasopharyngitis	5.5% 4/73	7.6% 6/79
Musculoskeletal and connective tissue disorders Pain in extremity	5.5% 4/73	6.3% 5/79
Infections and infestations Upper respiratory tract infection	5.5% 4/73	2.5% 2/79
Musculoskeletal and connective tissue disorders Back pain	4.1% 3/73	8.9% 7/79
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	4.1% 3/73	7.6% 6/79
Musculoskeletal and connective tissue disorders Arthralgia	2.7% 2/73	5.1% 4/79
General disorders Injection site bruising	1.4% 1/73	5.1% 4/79
Respiratory, thoracic and mediastinal disorders Sinus congestion	1.4% 1/73	6.3% 5/79

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