A Comparison of Adding Exenatide With Switching to Exenat... | NCT00870194

Status Module

Name	Class
Eli Lilly and Company	INDUSTRY

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

Name	Type	Description	Arm Group Labels	Other Names
exenatide and sitagliptin	Drug	exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; sitagliptin-100mg tablet orally once a day	1

Outcomes Module

Measure	Description	Time Frame
Change in HbA1c (Percent)	Change in HbA1c from baseline to endpoint (Week 20); difference of base percent values [X% - Y%]	Baseline to 20 Weeks

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Patients Achieving HbA1c <=7.0%	Percentage of patients whose baseline HbA1c was > 7.0% achieving HbA1c <=7.0% at endpoint (Week 20)	Baseline to 20 Weeks
Percentage of Patients Achieving HbA1c <7.0%

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Present with type 2 diabetes
Patients have been treated with a stable dose of the following for at least 3 months prior to screening:
- 100 mg/day sitagliptin and
- ≥1500 mg/day metformin, or maximum tolerated dose (extended release or immediate-release).
Have inadequate glycemic control as evidenced by an HbA1c between 7.1% and 9%, inclusive.
Have a body mass index (BMI) ≥20 kg/m2 and <45 kg/m2

Exclusion Criteria:

Are currently enrolled in, or discontinued within the last 30 days (or longer, if local guidelines require) from, a clinical trial involving an off-label use of an investigational drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
Have previously completed or withdrawn from this study or any other study investigating exenatide.
Have a known allergy or hypersensitivity to exenatide, sitagliptin or excipients contained in exenatide or sitagliptin.
Used drugs for weight loss (for example, orlistat, sibutramine, phenylpropanolamine, or similar over-the-counter medications) within 1 month of screening.
Are currently treated with any of the following excluded medications:
- Thiazolidinediones (TZD) within 3 months of screening.
- Sulfonylurea (SU) within 3 months of screening.
- Dipeptidyl peptidase-4 [DPP-4] inhibitors, with the exception of sitagliptin, within 3 months of screening.
- Meglitinide derivatives (for example, repaglinide or nateglinide) within 3 months of screening.
- Alpha-glucosidase inhibitors (for example, miglitol or acarbose) within 3 months of screening.
- Exogenous insulin within the 3 months prior to screening.
- Drugs that directly affect gastrointestinal motility, including, but not limited to: metoclopramide, cisapride, and chronic macrolide antibiotics.
- Systemic corticosteroids (excluding topical and inhaled preparations) by oral, intravenous (IV), or intramuscular (IM) route used regularly (for longer than 1 month) or used within 1 month immediately prior to screening.
- Any other oral antidiabetic (OAD) agent, other than sitagliptin or metformin, within 3 months prior to screening.

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

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Buenos Aires			Argentina
Research Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
22375612	Derived	Violante R, Oliveira JH, Yoon KH, Reed VA, Yu MB, Bachmann OP, Ludemann J, Chan JY. A randomized non-inferiority study comparing the addition of exenatide twice daily to sitagliptin or switching from sitagliptin to exenatide twice daily in patients with type 2 diabetes experiencing inadequate glycaemic control on metformin and sitagliptin. Diabet Med. 2012 Nov;29(11):e417-24. doi: 10.1111/j.1464-5491.2012.03624.x.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Exenatide + Placebo	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.
FG001	Exenatide + Sitagliptin

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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 (Percent)

Change in HbA1c from baseline to endpoint (Week 20); difference of base percent values [X% - Y%]

Per Protocol Set: the set of data generated by the subset of patients who sufficiently complied with the protocol to ensure that these data would be likely to exhibit the effects of treatment, according to the underlying scientific model.

Posted

Least Squares Mean

Standard Error

Percent HbA1c

Baseline to 20 Weeks

ID	Title	Description
OG000	Exenatide + Placebo	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.
OG001	Exenatide + Sitagliptin	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.

Units	Counts
Participants	OG00097 OG001111

Title

Denominators

Categories

Title	Measurements
	OG000-0.38± 0.09 OG001-0.68± 0.08

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		.012							95						Yes	Non-Inferiority or Equivalence	Non-Inferiority Margin of 0.4%
OG000 OG001	Power calculation: 80% assuming 200 patients (100 in each arm), no true difference and 1.0% standard deviation.

Secondary

Percentage of Patients Achieving HbA1c <=7.0%

Percentage of patients whose baseline HbA1c was > 7.0% achieving HbA1c <=7.0% at endpoint (Week 20)

Patients in the Per Protocol Set whose baseline HbA1c was > 7.0%; Last Observation Carried Forward.Per Protocol Set: the set of data generated by the subset of patients who sufficiently complied with the protocol to ensure that these data would be likely to exhibit the effects of treatment, according to the underlying scientific model.

Posted

Number

Percentage

Baseline to 20 Weeks

ID	Title	Description
OG000	Exenatide + Placebo	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.
OG001	Exenatide + Sitagliptin	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.

Units	Counts
Participants	OG000

Secondary

Percentage of Patients Achieving HbA1c <7.0%

Percentage of patients whose baseline HbA1c was >=7.0% achieving HbA1c <7.0% at endpoint (Week 20)

Patients in the Per Protocol Set whose baseline HbA1c was >= 7.0%; Last Observation Carried Forward. Per Protocol Set: the set of data generated by the subset of patients who sufficiently complied with the protocol to ensure that these data would be likely to exhibit the effects of treatment, according to the underlying scientific model.

Posted

Number

Percentage

Baseline to 20 Weeks

ID	Title	Description
OG000	Exenatide + Placebo	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.
OG001	Exenatide + Sitagliptin	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.

Units	Counts
Participants	OG000

Secondary

Percentage of Patients Achieving HbA1c <=6.5%

Percentage of patients whose baseline HbA1c was > 6.5% achieving HbA1c <=6.5% at endpoint (Week 20)

Patients in the Per Protocol Set whose baseline HbA1c was > 6.5%; Last Observation Carried Forward. Per Protocol Set: the set of data generated by the subset of patients who sufficiently complied with the protocol to ensure that these data would be likely to exhibit the effects of treatment, according to the underlying scientific model.

Posted

Number

Percentage

Baseline to 20 Weeks

ID	Title	Description
OG000	Exenatide + Placebo	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.
OG001	Exenatide + Sitagliptin	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.

Units	Counts
Participants	OG000

Secondary

Change in FSG (mmol/L)

Change in fasting serum glucose (FSG) from baseline to endpoint (Week 20)

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline to 20 Weeks

ID	Title	Description
OG000	Exenatide + Placebo	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.
OG001	Exenatide + Sitagliptin	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.

Units	Counts
Participants	OG000

Secondary

Change in Body Weight (kg)

Change in body weight from baseline to endpoint (Week 20)

Posted

Least Squares Mean

Standard Error

Baseline to 20 Weeks

ID	Title	Description
OG000	Exenatide + Placebo	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.
OG001	Exenatide + Sitagliptin	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.

Units	Counts
Participants	OG000

Secondary

Change in Waist Circumference (cm)

Change in waist circumference from baseline to endpoint (Week 20)

Posted

Least Squares Mean

Standard Error

Baseline to 20 Weeks

ID	Title	Description
OG000	Exenatide + Placebo	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.
OG001	Exenatide + Sitagliptin	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.

Units	Counts
Participants	OG000

Secondary

Waist-to-Hip Ratio

Change in waist-to-hip ratio from baseline to endpoint (Week20)

Posted

Least Squares Mean

Standard Error

Ratio

Baseline to 20 Weeks

ID	Title	Description
OG000	Exenatide + Placebo	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.
OG001	Exenatide + Sitagliptin	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.

Units	Counts
Participants	OG000

Secondary

SMBG (mmol/L)

7 point Self Monitored Blood Glucose Profiles - daily mean value (Week 20)

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline to 20 Weeks

ID	Title	Description
OG000	Exenatide + Placebo	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.
OG001	Exenatide + Sitagliptin	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.

Units	Counts
Participants	OG000

Secondary

Change in Triglycerides (mmol/L)

Change in triglycerides from baseline to endpoint (Week 20)

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline to 20 Weeks

ID	Title	Description
OG000	Exenatide + Placebo	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.
OG001	Exenatide + Sitagliptin	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.

Units	Counts
Participants	OG000

Secondary

Change in HDL (mmol/L)

Change in high-density lipoprotein (HDL) cholesterol from baseline to endpoint (Week 20)

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline to 20 Weeks

ID	Title	Description
OG000	Exenatide + Placebo	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.
OG001	Exenatide + Sitagliptin	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.

Units	Counts
Participants	OG000

Secondary

Change in LDL (mmol/L)

Change in low-density lipoprotein (LDL) cholesterol from baseline to endpoint (Week 20)

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline to 20 Weeks

ID	Title	Description
OG000	Exenatide + Placebo	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.
OG001	Exenatide + Sitagliptin	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.

Units	Counts
Participants	OG000

Secondary

Change in Total Cholesterol (mmol/L)

Change in total cholesterol from baseline to endpoint (Week 20)

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline to 20 Weeks

ID	Title	Description
OG000	Exenatide + Placebo	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.
OG001	Exenatide + Sitagliptin	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.

Units	Counts
Participants	OG000

Secondary

Incidence of Hypoglycemia (Overall)

Incidence of hypoglycemic episodes experienced overall during the study

As Treated Patients; Hypoglycemia defined as: patient experiencing a sign or symptom associated with hypoglycemia that is either self-treated or resolves on its own; not confirmed with blood glucose values.

Posted

Number

Participants

Baseline to 20 Weeks

ID	Title	Description
OG000	Exenatide + Placebo	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.
OG001	Exenatide + Sitagliptin	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.

Units	Counts
Participants	OG000

Secondary

Incidence of Severe Hypoglycemia(Overall)

Incidence of severe hypoglycemia experienced overall during the study

As Treated Patients; Severe hypo:symptoms consistent with hypoglycemia resulting in loss of consciousness or seizure with prompt recovery in response to administration of glucagon or glucose;or documented hypoglycemia (BG< 3.0 mmol/L [54/mg/dL]) requiring the assistance of another person because of severe impairment in consciousness or behavior

Posted

Number

Participants

Baseline to 20 Weeks

ID	Title	Description
OG000	Exenatide + Placebo	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.
OG001	Exenatide + Sitagliptin	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.

Units	Counts
Participants	OG000

Secondary

Incidence of Nocturnal Hypoglycemia (Overall)

Incidence of nocturnal hypoglycemia experienced overall during the study

As Treated Patients

Posted

Number

Participants

Baseline to 20 Weeks

ID	Title	Description
OG000	Exenatide + Placebo	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.
OG001	Exenatide + Sitagliptin	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.

Units	Counts
Participants	OG000

Secondary

Incidence of Confirmed Hypoglycemia(Overall)

Incidence of confirmed hypoglycemia experienced overall during the study

As Treated Patients; Hypoglycemia defined as: patient experiencing a sign or symptom associated with hypoglycemia that is either self-treated or resolves on its own; has a concurrent fingerstick blood glucose <3.0 mmol/L (54 mg/dL).

Posted

Number

Participants

Baseline to 20 Weeks

ID	Title	Description
OG000	Exenatide + Placebo	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.
OG001	Exenatide + Sitagliptin	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected128 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected128 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected127 at risk EG0011 affected128 at risk
Lumbar hernia	Gastrointestinal disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected128 at risk
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected128 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected128 at risk
Angina unstable	Cardiac disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected128 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected128 at risk
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected128 at risk
Coronary artery disease	Cardiac disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected128 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected128 at risk
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected128 at risk
Presyncope	Nervous system disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected128 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected128 at risk
Urosepsis	Infections and infestations	MedDRA 13.0	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected128 at risk

ID	Term
D003924	Diabetes Mellitus, Type 2
D003920	Diabetes Mellitus

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
D014230	Triazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011719	Pyrazines

ID	Title	Description
BG000	Exenatide + Placebo	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.
BG001	Exenatide + Sitagliptin	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.
BG002	Total	Total of all reporting 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 + Placebo	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.			4	127	36	127
EG001	Exenatide + Sitagliptin	Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.			6	128	28	128

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 13.0	Non-systematic Assessment	EG00020 affected127 at risk EG00113 affected128 at risk
Vomiting	Gastrointestinal disorders	MedDRA 13.0	Non-systematic Assessment	EG00013 affected127 at risk EG0014 affected128 at risk
Nasopharyngitis	Infections and infestations	MedDRA 13.0	Non-systematic Assessment	EG00011 affected127 at risk EG00110 affected128 at risk
Headache	Nervous system disorders	MedDRA 13.0	Non-systematic Assessment	EG0006 affected127 at risk EG0019 affected128 at risk