Efficacy of Exenatide Once Weekly and Once-Daily Insulin... | NCT00641056

NCT00641056

Status Module

Sponsor/Collaborators Module

Name	Class
Eli Lilly and Company	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
1	Experimental		Drug: Exenatide Once Weekly
2	Active Comparator		Drug: Insulin Glargine

Name	Type	Description	Arm Group Labels	Other Names
Exenatide Once Weekly	Drug	subcutaneous injection, 2.0mcg, once weekly	1

Outcomes Module

Measure	Description	Time Frame
Change in HbA1c From Baseline to Week 26	Change in HbA1c from baseline to Week 26	Baseline, Week 26

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Patients Achieving HbA1c <=7.0% at Week 26	Percentage of patients achieving HbA1c <=7.0% at Week 26 (for patients with HbA1c >7% at baseline)	Baseline, Week 26
Percentage of Patients Achieving HbA1c <=6.5% at Week 26

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Has type 2 diabetes and at least 18 years of age at screening.
Hemoglobin A1c (HbA1c) of 7.1% to 11.0%, inclusive, at screening.
Body mass index (BMI) of 25 kg/m2 to 45 kg/m2, inclusive, at screening.
Have a history of stable body weight (not varying by >5% for at least 3 months prior to screening).
Have been treated with metformin(Met) for at least 3 months and have been taking a stable dose for at least 8 weeks prior to screening OR
Have been treated with metformin(Met) for at least 3 months and have been taking a stable dose for at least 8 weeks prior to screening and have been treated with SU for at least 3 months and have been taking a stable dose of at least an optimally effective dose of brand of SU for 8 weeks prior to screening.

Exclusion Criteria:

Have had a clinically significant history of cardiac disease or presence of active cardiac disease within the year prior to inclusion in the study, 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 clinical signs or symptoms of liver disease, acute or chronic hepatitis.
Have a history of renal transplantation or are currently receiving renal dialysis.
Have 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 had greater than three episodes of major hypoglycemia within 6 months prior to screening.
Have any contraindication for the oral antidiabetic agent which they use.
Have a known allergy or hypersensitivity to insulin glargine, exenatide once weekly, or excipients contained in these agents.
Are known to have active proliferative retinopathy.
Have been treated with drugs that promote weight loss (e.g., Xenical® [orlistat], Meridia® [sibutramine], Acomplia® [rimonabant], Acutrim® [phenylpropanolamine], or similar over-the-counter medications) within 3 months of screening.
Have been treated for longer than 2 weeks with any of the following excluded medications within 3 months prior to screening:
- Insulin
- Thiazolidinediones (e.g., Actos® [pioglitazone] or Avandia® [rosiglitazone])
- Alpha-glucosidase inhibitors (e.g., Glyset® [miglitol] or Precose® [acarbose])
- Meglitinides (e.g., Prandin® [repaglinide] or Starlix® [nateglinide]).
- Byetta® (exenatide BID formulation)
- Dipeptidyl peptidase (DPP)-4 inhibitors (e.g., Januvia™ [sitagliptin], Galvus® [vildagliptin])
- Symlin® (pramlintide acetate).
Have had an organ transplant.
Have donated blood within 30 days of screening.
Have previously completed or withdrawn from this study or any other study investigating exenatide once weekly.
Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
Are currently enrolled in any other clinical study.

Contacts/Locations Module

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

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Escondido	California		United States
Research Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
22357185	Result	Diamant M, Van Gaal L, Stranks S, Guerci B, MacConell L, Haber H, Scism-Bacon J, Trautmann M. Safety and efficacy of once-weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes over 84 weeks. Diabetes Care. 2012 Apr;35(4):683-9. doi: 10.2337/dc11-1233. Epub 2012 Feb 22.
32306296	Derived

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Exenatide Once Weekly	Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.
FG001	Insulin Glargine	Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Percentage of patients achieving HbA1c <=6.5% at Week 26 (for patients with HbA1c >6.5% at baseline)

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Exenatide Once Weekly	Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.
BG001	Insulin Glargine	Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020
Between 18 and 65 years

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00057.6± 9.72 BG00158.3± 9.08 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000113 BG001100 BG002

Glycosylated hemoglobin (HbA1c)

Mean

Standard Deviation

percentage of total hemoglobin

Title

Denominators

Categories

Title	Measurements
	BG0008.32± 1.094 BG0018.29± 1.020 BG002

Weight

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00091.22± 18.582 BG00190.56± 16.348 BG002

Background Oral Antidiabetic Agent (OAD)

Number

participants

Title

Denominators

Categories

Metformin (Met)

Title	Measurements
	BG000164 BG001157 BG002

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

Change in HbA1c From Baseline to Week 26

Change in HbA1c from baseline to Week 26

ITT Population: All randomized patients who had taken at least one dose of study drug. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Posted

Least Squares Mean

Standard Error

percentage of total hemoglobin

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.
OG001	Insulin Glargine	Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.

Units	Counts
Participants	OG000205 OG001206

Title

Denominators

Categories

Title	Measurements
	OG000-1.47± 0.05 OG001-1.31± 0.06

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	Mixed-model Repeated Measures (MMRM) Analysis of Covariance (ANCOVA) model includes treatment, baseline HbA1c, country, background OAD stratum, week of visit, and treatment-by-week interaction as fixed effects; patient and error as random effects. Superiority of exenatide once weekly to insulin glargine is concluded if the upper limit of the 95% confidence interval for the treatment difference [exenatide once weekly-insulin glargine]<0; noninferiority is concluded if this upper limit<0.3%.	Mixed Models Analysis		0.017	No adjustments for multiplicity were performed	Least Squares Mean Difference	-0.16	Standard Error of the Mean	0.07	2-Sided	95	-0.29	-0.03				Yes

Secondary

Percentage of Patients Achieving HbA1c <=7.0% at Week 26

Percentage of patients achieving HbA1c <=7.0% at Week 26 (for patients with HbA1c >7% at baseline)

ITT Population. Only patients with baseline HbA1c > 7% were included in calculation. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Posted

Number

percentage of patients

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.
OG001	Insulin Glargine	Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.

Units	Counts
Participants

Secondary

Percentage of Patients Achieving HbA1c <=6.5% at Week 26

Percentage of patients achieving HbA1c <=6.5% at Week 26 (for patients with HbA1c >6.5% at baseline)

ITT Population. Only patients with baseline HbA1c > 6.5% were included in calculation. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Posted

Number

percentage of patients

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.
OG001	Insulin Glargine	Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.

Units	Counts
Participants

Secondary

Change in Fasting Serum Glucose (FSG) From Baseline to Week 26

Change in FSG (mmol/L) from Baseline to Week 26

ITT Population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.
OG001	Insulin Glargine	Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.

Units	Counts
Participants	OG000

Secondary

Change in Body Weight (BW) From Baseline to Week 26

Change in BW (kg) from Baseline to Week 26

ITT Population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Posted

Least Squares Mean

Standard Error

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.
OG001	Insulin Glargine	Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.

Units	Counts
Participants	OG000

Secondary

Change in Total Cholesterol From Baseline to Week 26

Change in Total Cholesterol (mmol/L) from Baseline to Week 26

ITT Population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.
OG001	Insulin Glargine	Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.

Units	Counts
Participants	OG000

Secondary

Change in High-density Lipoprotein Cholesterol (HDL) From Baseline to Week 26

Change in HDL (mmol/L) from Baseline to Week 26

ITT Population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.
OG001	Insulin Glargine	Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.

Units	Counts
Participants	OG000

Secondary

Ratio of Triglycerides at Week 26 to Baseline

Ratio of Triglycerides (measured in mmol/L) at Week 26 to Baseline. Log (Postbaseline Triglycerides) - log (Baseline Triglycerides); change from baseline to endpoint is presented as ratio of endpoint to baseline.

ITT Population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Posted

Least Squares Mean

Standard Error

ratio

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.
OG001	Insulin Glargine	Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.

Units	Counts
Participants

Secondary

Change in Blood Pressure From Baseline to Week 26

Change in Systolic Blood Pressure (mmHg) and Diastolic Blood Pressure (mmHg) from Baseline to Week 26

ITT Population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Posted

Mean

Standard Deviation

mmHg

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.
OG001	Insulin Glargine	Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.

Units	Counts
Participants	OG000

Secondary

Assessment on Event Rate of Treatment-emergent Hypoglycemic Episodes

Major hypoglycemia: any episode with symptoms consistent with hypoglycemia that resulted in loss of consciousness or seizure with prompt recovery in response to administration of glucagon or glucose or documented hypoglycemia (blood glucose <3.0 mmol/L [54 mg/dL]) and required the assistance of another person. Minor hypoglycemia: any time a patient felt that he or she was experiencing a sign or symptom of hypoglycemia that was self-treated or resolved on its own and had a blood glucose level <3.0 mmol/L (54 mg/dL) and not classified as major hypoglycemia.

ITT Population.

Posted

Mean

Standard Error

rate per subject-year

Baseline to Week 26

ID	Title	Description
OG000	Exenatide Once Weekly With SU	Patients assigned to the Exenatide Once Weekly With SU group received a 2 mg dose of exenatide injected once a week and took concomitant Met+SU.
OG001	Insulin Glargine With SU	Patients assigned to the Insulin Glargine with SU group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L and took concomitant Met+SU.
OG002	Exenatide Once Weekly No SU

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Exenatide Once Weekly	Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.			11	233	100	233
EG001	Insulin Glargine	Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.			10	223	52	223

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute coronary syndrome	Cardiac disorders	MedDRA 12.0	Non-systematic Assessment	EG0001 affected233 at risk EG0010 affected223 at risk
Atrioventricular block	Cardiac disorders	MedDRA 12.0	Non-systematic Assessment	EG0001 affected233 at risk EG0010 affected223 at risk
Cardiac arrest	Cardiac disorders	MedDRA 12.0	Non-systematic Assessment	EG0001 affected233 at risk EG0010 affected223 at risk
Cardioversion	Surgical and medical procedures	MedDRA 12.0	Non-systematic Assessment	EG0001 affected233 at risk EG0010 affected223 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 12.0	Non-systematic Assessment	EG0001 affected233 at risk EG0010 affected223 at risk
Chest pain	General disorders	MedDRA 12.0	Non-systematic Assessment	EG0001 affected233 at risk EG0012 affected223 at risk
Drug exposure during pregnancy	Injury, poisoning and procedural complications	MedDRA 12.0	Non-systematic Assessment	EG0001 affected233 at risk EG0010 affected223 at risk
Haematoma	Vascular disorders	MedDRA 12.0	Non-systematic Assessment	EG0001 affected233 at risk EG0010 affected223 at risk
Injection site nodule	General disorders	MedDRA 12.0	Non-systematic Assessment	EG0001 affected233 at risk EG0010 affected223 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 12.0	Non-systematic Assessment	EG0001 affected233 at risk EG0010 affected223 at risk
Oedematous pancreatitis	Gastrointestinal disorders	MedDRA 12.0	Non-systematic Assessment	EG0001 affected233 at risk EG0010 affected223 at risk
Urinary tract infection	Infections and infestations	MedDRA 12.0	Non-systematic Assessment	EG0001 affected233 at risk EG0010 affected223 at risk
Viral pericarditis	Infections and infestations	MedDRA 12.0	Non-systematic Assessment	EG0001 affected233 at risk EG0010 affected223 at risk
Vitrectomy	Surgical and medical procedures	MedDRA 12.0	Non-systematic Assessment	EG0001 affected233 at risk EG0010 affected223 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 12.0	Non-systematic Assessment	EG0000 affected233 at risk EG0011 affected223 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA 12.0	Non-systematic Assessment	EG0000 affected233 at risk EG0011 affected223 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA 12.0	Non-systematic Assessment	EG0000 affected233 at risk EG0011 affected223 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 12.0	Non-systematic Assessment	EG0000 affected233 at risk EG0011 affected223 at risk
Colon polypectomy	Surgical and medical procedures	MedDRA 12.0	Non-systematic Assessment	EG0000 affected233 at risk EG0011 affected223 at risk
Myocarditis	Cardiac disorders	MedDRA 12.0	Non-systematic Assessment	EG0000 affected233 at risk EG0011 affected223 at risk
Peripheral nerve transposition	Surgical and medical procedures	MedDRA 12.0	Non-systematic Assessment	EG0000 affected233 at risk EG0011 affected223 at risk
Presyncope	Nervous system disorders	MedDRA 12.0	Non-systematic Assessment	EG0000 affected233 at risk EG0011 affected223 at risk
Retinal detachment	Eye disorders	MedDRA 12.0	Non-systematic Assessment	EG0000 affected233 at risk EG0011 affected223 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 12.0	Non-systematic Assessment	EG00030 affected233 at risk EG00139 affected223 at risk
Nausea	Gastrointestinal disorders	MedDRA 12.0	Non-systematic Assessment	EG00030 affected233 at risk EG0013 affected223 at risk
Headache	Nervous system disorders	MedDRA 12.0	Non-systematic Assessment	EG00023 affected233 at risk EG00116 affected223 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 12.0	Non-systematic Assessment	EG00020 affected233 at risk EG0018 affected223 at risk
Injection site nodule	General disorders	MedDRA 12.0	Non-systematic Assessment	EG00012 affected233 at risk EG0010 affected223 at risk

ID	Term
D003924	Diabetes Mellitus, Type 2
D003920	Diabetes Mellitus

ID	Term
D000069036	Insulin Glargine

Ancestor Terms

ID	Term
D049528	Insulin, Long-Acting
D061385	Insulins
D010187	Pancreatic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins

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