Effect of Exenatide on Abdominal Fat Distribution in Pati... | NCT00701935

Name	Class
Eli Lilly and Company	INDUSTRY

Label	Type	Description	Intervention Names
1	Placebo Comparator		Drug: placebo
2	Experimental		Drug: exenatide

Name	Type	Description	Arm Group Labels	Other Names
placebo	Drug	subcutaneous injection, twice a day	1
exenatide

Measure	Description	Time Frame
Percentage Change in Abdominal Visceral Fat From Baseline to 6 Months	Percentage change in abdominal visceral fat	baseline, 6 months

Measure	Description	Time Frame
Percentage Change in Total Abdominal Fat From Baseline to 6 Months	Percentage change in total abdominal fat	baseline, 6 months
Percentage Change in Subcutaneous Abdominal Fat From Baseline to 6 Months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients between 18 and 85 years of age, inclusive.
Patients with type 2 diabetes
Patients have been treated with metformin, at a stable dose for at least 3 months prior to Visit 1
Patients have HbA1c of 7.0% to 8.9%, inclusive.
Patients have a body mass index >27 kg/m2 and <40 kg/m2 and meet local CT scan body weight requirements. For South Asian, Japanese, and Chinese patients, a body mass index >=25 kg/m2 is acceptable as the lower limit.
Patients have a history of stable body weight (not varying by >2 kg in the 3 months prior to Visit 1).
Medications for the treatment of high blood pressure are stable with respect to treatment regimen for 4 weeks prior to Visit 1.
Stable regimen of lipid-lowering agents for 6 weeks prior to Visit 1.

Exclusion Criteria:

Have received treatment in the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
Have an active or untreated malignancy, or have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years.
Have a history of renal transplantation, or are currently receiving renal dialysis.
Have had a clinically significant history of cardiac disease or presence of active cardiac disease within 1 year prior to Visit 1, including myocardial infarction, clinically significant arrhythmia, unstable angina, moderate to severe congestive heart failure, coronary artery bypass surgery, or angioplasty; or is expected to require coronary artery bypass surgery or angioplasty during the course of the study.
Have known hemoglobinopathy or clinically significant, chronic anemia.
Known or are likely to become transfusion dependent during the study.
Have active, symptomatic proliferative retinopathy.
Are receiving chronic treatment for gastrointestinal disease with a drug directly affecting gastrointestinal motility. (i.e. metoclopramide, cisapride, and chronic use of macrolide antibiotics)
Have severe gastrointestinal disease, including gastroparesis.
Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 months immediately prior to Visit 1.
Have taken exenatide, liraglutide or any other GLP-1 receptor agonist in the past 6 months, either in a clinical study or as commercially available medication. Patients with known allergy to exenatide should be excluded.
Have used any prescription or over the counter drug to promote weight loss within 3 months prior to Visit 1, or intend to use such a drug during the study. (Examples: Xenical [orlistat], Meridia [sibutramine], Acutrim [phenylpropanolamine], Acomplia [rimonabant]).
Have participated in a structured weight loss program within 3 months prior to Visit 1, or intend to participate in such a plan during this study.
Have been treated for longer than 2 weeks with any of the following excluded medications within 3 months prior to Visit 1: Insulin; Thiazolidinediones; Alpha-glucosidase inhibitors; Sulfonylureas; Oral DPP-IV inhibitors; Meglitinides.
Are taking warfarin, or a coumarol derivative.

Name	Affiliation	Role
Chief Medical Officer, MD Eli Lilly and Company	Eli Lilly and Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Temple	Arizona		United States
Research Site

ID	Title	Description
FG000	Exenatide BID	Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for remainder of 6 months)
FG001	Placebo

ID	Title	Description
BG000	Exenatide BID	Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for remainder of 6 months)
BG001	Placebo	Subcutaneous injection of placebo twice a day for 6 months
BG002	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage Change in Abdominal Visceral Fat From Baseline to 6 Months

Percentage change in abdominal visceral fat

Primary analysis done on the Intent To Treat (ITT) Population including all randomized patients receiving at least one dose of study drug according to the treatment the subjects are randomized to regardless of what study drug patients received

Posted

Least Squares Mean

Standard Error

% change

baseline, 6 months

ID	Title	Description
OG000	Exenatide BID	Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for remainder of 6 months)
OG001	Placebo	Subcutaneous injection of placebo twice a day for 6 months

Units	Counts
Participants	OG00029 OG00127

Title

Denominators

Categories

Title	Measurements
	OG000-5.28± 3.23 OG001-4.30± 3.53

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The power calculation is based on a two-sided t-test and significance level of 0.05. Hypotheses for sample size: Power: 80% Drop-out rate: 20% Difference in the percentage change in abdominal visceral fat from baseline to 6 months between exenatide and placebo: 10% Common standard deviation: 15% 94 patients are needed to attain the 37 patients randomized and analyzed in each group.	ANCOVA	The ANCOVA model includes terms of treatment, gender, investigator and baseline abdominal visceral fat.	0.8252	p-values were not adjusted for multiple comparisons.	Mean Difference (Final Values)	-0.98	Standard Error of the Mean	4.432	2-Sided	95	-9.92	7.95

Secondary

Percentage Change in Total Abdominal Fat From Baseline to 6 Months

Percentage change in total abdominal fat

Analysis done on the ITT Population including all randomized patients receiving at least one dose of study drug according to the treatment the subjects are randomized to regardless of what study drug patients received

Posted

Least Squares Mean

Standard Error

% change

baseline, 6 months

ID	Title	Description
OG000	Exenatide BID	Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for remainder of 6 months)
OG001	Placebo	Subcutaneous injection of placebo twice a day for 6 months

Units	Counts
Participants	OG000

Secondary

Percentage Change in Subcutaneous Abdominal Fat From Baseline to 6 Months

Percentage change in subcutaneous abdominal fat

Posted

Least Squares Mean

Standard Error

% change

baseline, 6 months

ID	Title	Description
OG000	Exenatide BID	Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for remainder of 6 months)
OG001	Placebo	Subcutaneous injection of placebo twice a day for 6 months

Units	Counts
Participants	OG000

Secondary

Change in HbA1c From Baseline to 6 Months

Change in HbA1c from baseline to 6 months. HbA1c is a measurement of the amount of hemogobin that is glycosylated.

Posted

Least Squares Mean

Standard Error

% change

baseline, 6 months

ID	Title	Description
OG000	Exenatide BID	Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for remainder of 6 months)
OG001	Placebo	Subcutaneous injection of placebo twice a day for 6 months

Units	Counts
Participants	OG000

Secondary

Percentage of Patients With HbA1c <=7.0% at 6 Months

Percentage of patients with HbA1c values <= 7.0% measured at 6 months. HbA1c is a measurement of the amount of hemogobin that is glycosylated.

Posted

Number

Percentage of patients

6 months

ID	Title	Description
OG000	Exenatide BID	Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for remainder of 6 months)
OG001	Placebo	Subcutaneous injection of placebo twice a day for 6 months

Units	Counts
Participants	OG000

Secondary

Change in Fasting Plasma Glucose From Baseline to 6 Months

Change in Fasting plasma glucose

Posted

Least Squares Mean

Standard Error

mmol/L

baseline, 6 months

ID	Title	Description
OG000	Exenatide BID	Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for remainder of 6 months)
OG001	Placebo	Subcutaneous injection of placebo twice a day for 6 months

Units	Counts
Participants	OG000

Secondary

Change in Weight From Baseline to 6 Months

Change in weight

Posted

Least Squares Mean

Standard Error

baseline, 6 months

ID	Title	Description
OG000	Exenatide BID	Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for remainder of 6 months)
OG001	Placebo	Subcutaneous injection of placebo twice a day for 6 months

Units	Counts
Participants	OG000

Secondary

Change in Systolic Blood Pressure From Baseline to 6 Months

Change in Systolic blood pressure

Analysis done on the ITT Population including all randomized patients receiving at least one dose of study drug.

Posted

Mean

Standard Deviation

mmHg

baseline, 6 months

ID	Title	Description
OG000	Exenatide BID	Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for remainder of 6 months)
OG001	Placebo	Subcutaneous injection of placebo twice a day for 6 months

Units	Counts
Participants	OG000

Secondary

Change in Diastolic Blood Pressure From Baseline to 6 Months

Change in Diastolic blood pressure

Analysis done on the ITT Population including all randomized patients receiving at least one dose of study drug.

Posted

Mean

Standard Deviation

mmHg

baseline, 6 months

ID	Title	Description
OG000	Exenatide BID	Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for remainder of 6 months)
OG001	Placebo	Subcutaneous injection of placebo twice a day for 6 months

Units	Counts
Participants	OG000

Secondary

Change in Total Cholesterol From Baseline to 6 Months

Change in total cholesterol

Posted

Least Squares Mean

Standard Error

mmol/L

baseline, 6 months

ID	Title	Description
OG000	Exenatide BID	Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for remainder of 6 months)
OG001	Placebo	Subcutaneous injection of placebo twice a day for 6 months

Units	Counts
Participants	OG000

Secondary

Change in Triglycerides From Baseline to 6 Months

Change in triglycerides

Posted

Least Squares Mean

Standard Error

mmol/L

baseline, 6 months

ID	Title	Description
OG000	Exenatide BID	Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for remainder of 6 months)
OG001	Placebo	Subcutaneous injection of placebo twice a day for 6 months

Units	Counts
Participants	OG000

Secondary

Change in High-Density Lipoprotein (HDL) Cholesterol From Baseline to 6 Months

Change in HDL cholesterol

Posted

Least Squares Mean

Standard Error

mmol/L

baseline, 6 months

ID	Title	Description
OG000	Exenatide BID	Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for remainder of 6 months)
OG001	Placebo	Subcutaneous injection of placebo twice a day for 6 months

Units	Counts
Participants	OG000

Secondary

Assessment of Event Rate of Treatment- Emergent Hypoglycemic Event

All hypoglycemia episodes defined as major (results in loss of consciousness, seizure or coma resolving after administration of glucagon or glucose OR needing third-party assistance to resolve due to severe impairment in consciousness and associated with glucose concentration < 2.8 mol/L.) or minor (non-major event with symptoms consistent with hypoglycemia and glucose value < 2.8 mmol/L prior to treating) or symptoms of hypoglycemia (does not meet the criteria for a major or minor event).

Analysis done on the ITT Population including all randomized patients receiving at least one dose of study drug.

Posted

Mean

Standard Error

hypoglycemia rate/year

baseline, 6 months

ID	Title	Description
OG000	Exenatide BID	Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for remainder of 6 months)
OG001	Placebo	Subcutaneous injection of placebo twice a day for 6 months

Units	Counts
Participants

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
vertigo	Ear and labyrinth disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 affected43 at risk EG0010 affected37 at risk
Nausea	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG00015 affected43 at risk EG00111 affected37 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0007 affected43 at risk EG0011 affected37 at risk
Vomiting	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0007 affected43 at risk EG0013 affected37 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0004 affected43 at risk EG0011 affected37 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected43 at risk EG0016 affected37 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected43 at risk EG0012 affected37 at risk
Fatigue	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG0005 affected43 at risk EG0011 affected37 at risk
Injection site reaction	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected43 at risk EG0012 affected37 at risk
Nasopharyngitis	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0008 affected43 at risk EG0017 affected37 at risk
Influenza	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0003 affected43 at risk EG0012 affected37 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (15.0)	Non-systematic Assessment	EG0008 affected43 at risk EG0014 affected37 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected43 at risk EG0012 affected37 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 affected43 at risk EG0012 affected37 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 affected43 at risk EG0010 affected37 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected43 at risk EG0013 affected37 at risk
Headache	Nervous system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0006 affected43 at risk EG0015 affected37 at risk
Dizziness	Nervous system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 affected43 at risk EG0013 affected37 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected43 at risk EG0012 affected37 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected43 at risk EG0012 affected37 at risk

ID	Term
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D014688	Venoms
D045424	Complex Mixtures
D014118	Toxins, Biological
D001685	Biological Factors

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Exenatide BID	Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for remainder of 6 months)			3	43	38	43
EG001	Placebo	Subcutaneous injection of placebo twice a day for 6 months			1	37	25	37

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected43 at risk EG0011 affected37 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected43 at risk EG0011 affected37 at risk
Myocardial infarction	Cardiac disorders	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected43 at risk EG0011 affected37 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected37 at risk
Mesenteritis	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected37 at risk
Malaise	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG0000 affected43 at risk EG0011 affected37 at risk
Diverticulitis	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected37 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 affected43 at risk EG0010 affected37 at risk