Efficacy of Once-Weekly Exenatide Versus Once or Twice Da... | NCT01003184

NCT01003184

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 detemir

Name	Type	Description	Arm Group Labels	Other Names
exenatide once weekly	Drug	subcutaneous injection, 2mg, once a week	1

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Patients Achieving Glycosylated Hemoglobin (HbA1c) Concentration ≤7.0% With Weight Loss (≥1.0 kg) at Endpoint (Week 26)	The primary endpoint is the percentage of patients achieving HbA1c concentration ≤7.0% with weight loss (≥1.0 kg) at endpoint. The last post-baseline measurement set of both non-missing HbA1c concentration and weight (measured at the same time point, i.e. visit) is used as endpoint value. Patients who do not have a baseline weight measurement, have a protocol violation of baseline HbA1c <=7.0%, and/or have missing post-baseline measurements for HbA1c concentration and/or weight, are included in the analysis as non-responders regarding the primary objective.	Baseline, Week 26

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Patients Who Have Achieved HbA1c ≤7.4% With Weight Loss (≥1.0 kg) at Endpoint (Week 26)	Percentage of patients who have achieved HbA1c ≤7.4% with weight loss (≥1.0 kg) at endpoint (Week 26)	Baseline, Week 26
Change in HbA1c From Baseline to Week 26

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Have suboptimal glycaemic control as evidenced by an HbA1c 7.1% to 10.0%, inclusive
Have a body mass index (BMI) of 25 kg/m2 to 45 kg/m2, inclusive
Are receiving metformin at a stable dose (consistent with country specific requirements) of a minimum of 1000mg for at least 3 months prior to start start OR are receiving metformin at a minimum dose (consistent with country specific requirements) of 1000mg and sulphonylurea (as separate medications not as a fixed dose combination) at stable doses for 3 months prior to study start

Exclusion Criteria:

Have any contraindication for the OAD that they have been using
Have a known allergy or hypersensitivity to insulin detemir, exenatide or excipients contained in these agents
Have been treated within 4 weeks of screening with systemic glucocorticoid therapy by oral, intravenous (IV) or intramuscular (IM) route, or are regularly treated with potent, inhaled intranasal steroids that are known to have a high rate of systemic absorption. Exceptions to this criterion include patients who are receiving glucocorticoid therapy for corticotropic hypopituitary deficiency (e.g. Addison disease)
Have been treated with drugs that promote weight loss, 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, alpha-glucosidase, Byetta® (exenatide BID formulation), thiazolidinediones (TZD), dipeptidyl peptidase (DPP)-4 inhibitors
Have previously completed or withdrawn from this study or any other study investigating exenatide QW
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, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device (other than the study drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this 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		Dublin			Ireland
Research Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
32306296	Derived	Guja C, Frias JP, Suchower L, Hardy E, Marr G, Sjostrom CD, Jabbour SA. Safety and Efficacy of Exenatide Once Weekly in Participants with Type 2 Diabetes and Stage 2/3 Chronic Kidney Disease. Diabetes Ther. 2020 Jul;11(7):1467-1480. doi: 10.1007/s13300-020-00815-z. Epub 2020 Apr 18.

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	Exenatide once weekly : subcutaneous injection, 2mg, once a week
FG001	Insulin Detemir	Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

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

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Exenatide Once Weekly	Exenatide once weekly : subcutaneous injection, 2mg, once a week
BG001	Insulin Detemir	Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day
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
	BG00059.2± 9.86 BG00157.8± 9.48 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00040 BG00133 BG002

HbA1c

At visit 3 (week 0).

Mean

Standard Deviation

Percentage of total hemoglobin

Title

Denominators

Categories

Title	Measurements
	BG0008.4± 0.85 BG0018.4± 0.88 BG002

Weight

Mean

Standard Deviation

Kilograms

Title

Denominators

Categories

Title	Measurements
	BG00096.7± 17.03 BG00197.9± 15.82 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

Percentage of Patients Achieving Glycosylated Hemoglobin (HbA1c) Concentration ≤7.0% With Weight Loss (≥1.0 kg) at Endpoint (Week 26)

The primary endpoint is the percentage of patients achieving HbA1c concentration ≤7.0% with weight loss (≥1.0 kg) at endpoint. The last post-baseline measurement set of both non-missing HbA1c concentration and weight (measured at the same time point, i.e. visit) is used as endpoint value. Patients who do not have a baseline weight measurement, have a protocol violation of baseline HbA1c <=7.0%, and/or have missing post-baseline measurements for HbA1c concentration and/or weight, are included in the analysis as non-responders regarding the primary objective.

The full analysis set (FAS) includes all data from all randomised patients receiving at least one dose of the study drug according to the treatment the patients were assigned.

Posted

Number

95% Confidence Interval

Percentage

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly : subcutaneous injection, 2mg, once a week
OG001	Insulin Detemir	Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Units	Counts
Participants	OG000111 OG001105

Title

Denominators

Categories

Title	Measurements
	OG00044.1(34.7 to 53.9) OG00111.4(6.0 to 19.1)

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	Primary objective: to test hypothesis that the percentage of patients with HbA1c ≤7.0% with weight loss (≥1.0 kg) after exenatide QW is superior to insulin detemir. Sample size estimation: based on the test for difference in percentage between Exenatide QW and insulin detemir. Assuming: common drop-out rate 20%, response rate at endpoint 50% in the exenatide QW group and 25% in the insulin detemir group; 5% significance. 214 patients will provide 90% power to detect a difference.	Regression, Logistic	Logistic regression model includes treatment group, use of SU (yes/no), baseline HbA1c and baseline weight as main factors.	<.0001		Odds Ratio (OR)	6.60			2-Sided	95	3.17	13.73				No

Secondary

Percentage of Patients Who Have Achieved HbA1c ≤7.4% With Weight Loss (≥1.0 kg) at Endpoint (Week 26)

Percentage of patients who have achieved HbA1c ≤7.4% with weight loss (≥1.0 kg) at endpoint (Week 26)

The analysis was done for the FAS population (as randomised). For secondary analyses including both final HbA1c concentration and change in weight the last post-baseline measurement set of both non-missing HbA1c and weight was used as endpoint value.

Posted

Number

95% Confidence Interval

Percentage

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly : subcutaneous injection, 2mg, once a week
OG001	Insulin Detemir	Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Units	Counts
Participants	OG000

Secondary

Change in HbA1c From Baseline to Week 26

Change in HbA1c from baseline to week 26

The analysis was done for the FAS population (as randomised).

Posted

Least Squares Mean

Standard Error

Percentage of total hemoglobin

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly : subcutaneous injection, 2mg, once a week
OG001	Insulin Detemir	Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Units	Counts
Participants	OG000

Secondary

Change in Body Weight From Baseline to Week 26

Change in body weight from baseline to week 26

The analysis was done for the FAS population (as randomised).

Posted

Least Squares Mean

Standard Error

kilograms

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly : subcutaneous injection, 2mg, once a week
OG001	Insulin Detemir	Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Units	Counts
Participants	OG000

Secondary

Percentage of Patients Achieving HbA1c ≤7.4% at Endpoint

Percentage of patients who have achieved HbA1c ≤.7.4% at endpoint

The analysis was done for the FAS population (as randomised). Patients with baseline HbA1c ≤7.0% and/or no post-baseline HbA1c measurement were regarded as non-responders.

Posted

Number

95% Confidence Interval

Percentage

Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly : subcutaneous injection, 2mg, once a week
OG001	Insulin Detemir	Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Units	Counts
Participants	OG000

Secondary

Percentage of Patients Achieving ≤7.0% at Endpoint

Percentage of patients achieving ≤7.0% at endpoint.

The analysis was done for the FAS population (as randomised). Patients with baseline HbA1c ≤7.0% and/or no post-baseline HbA1c measurement were regarded as non-responders.

Posted

Number

95% Confidence Interval

Percentage

Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly : subcutaneous injection, 2mg, once a week
OG001	Insulin Detemir	Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Units	Counts
Participants	OG000

Secondary

Percentage of Patients Achieving ≤6.5% at Endpoint

Percentage of patients achieving HbA1c ≤6.5% at endpoint

The analysis was done for the FAS population (as randomised). Patients with baseline HbA1c ≤7.0% and/or no post-baseline HbA1c measurement were regarded as non-responders.

Posted

Number

95% Confidence Interval

Percentage

Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly : subcutaneous injection, 2mg, once a week
OG001	Insulin Detemir	Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Units	Counts
Participants	OG000

Secondary

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

Change in fasting serum glucose from baseline to endpoint (Week 26).

The analysis was done for the FAS population (as randomised).

The last observation carried forward (LOCF) of post baseline values was used for this analysis.

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly : subcutaneous injection, 2mg, once a week
OG001	Insulin Detemir	Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Units	Counts
Participants	OG000

Secondary

Changes in Systolic Blood Pressure From Baseline to Week 26

Change in systolic blood pressure from baseline to Week 26

The analysis was done for the FAS population (as randomised).

Posted

Least Squares Mean

Standard Error

mmHg

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly : subcutaneous injection, 2mg, once a week
OG001	Insulin Detemir	Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Units	Counts
Participants	OG000

Secondary

Change in Diastolic Blood Pressure From Baseline to Week 26.

Change in diastolic blood pressure from baseline to week 26.

The analysis was done for the FAS population (as randomised).

Posted

Least Squares Mean

Standard Error

mmHg

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly : subcutaneous injection, 2mg, once a week
OG001	Insulin Detemir	Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Units	Counts
Participants	OG000

Secondary

Change in Total Cholesterol From Baseline to Endpoint (Week 26).

Change in total cholesterol from baseline to endpoint (week 26).

The analysis was done for the FAS population (as randomised).

The last observation carried forward (LOCF) of post baseline values was used for this analysis.

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly : subcutaneous injection, 2mg, once a week
OG001	Insulin Detemir	Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Units	Counts
Participants	OG000

Secondary

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

Change in High-density lipoprotein (HDL) cholesterol from baseline to endpoint (week 26).

The analysis was done for the FAS population (as randomised). The last observation carried forward (LOCF) of post baseline values was used for this analysis.

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly : subcutaneous injection, 2mg, once a week
OG001	Insulin Detemir	Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Units	Counts
Participants	OG000

Secondary

Change in Triglycerides From Baseline to Endpoint (Week 26).

Change in triglycerides from baseline to endpoint (week 26).

The analysis was done for the FAS population (as randomised). The last observation carried forward (LOCF) of post baseline values was used for this analysis.

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly : subcutaneous injection, 2mg, once a week
OG001	Insulin Detemir	Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Units	Counts
Participants	OG000

Secondary

Hypoglycemia Rate Per Year

All confirmed hypoglycemia episodes defined as either minor (any time a patient feels that he or she is experiencing a sign or symptom associated with hypoglycaemia and blood glucose (BG) <3.0 mmol/L (54 mg/dL)) or major (any hypoglycaemic episode with symptoms consistent with hypoglycaemia, resulting in loss of consciousness or seizure, and shows prompt recovery in response to administration of glucagon or glucose, or BG measurement < 3.0mmol/L is available and the patient is not capable of self-treating were taken into account.

Full analysis set (as randomized).

Posted

Number

95% Confidence Interval

events per subject-year

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly : subcutaneous injection, 2mg, once a week
OG001	Insulin Detemir	Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Units	Counts
Participants

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	Exenatide once weekly : subcutaneous injection, 2mg, once a week			6	111	87	111
EG001	Insulin Detemir	Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day			6	105	58	105

Serious Adverse Events

Term	Organ System	Source Vocabulary	Statistical Information
Atrioventricular block second degree	Cardiac disorders	MedDRA 14.0	EG0001 affected111 at risk EG0010 affected105 at risk
Ventricular extrasystoles	Cardiac disorders	MedDRA 14.0	EG0001 affected111 at risk EG0010 affected105 at risk
Chest discomfort	General disorders	MedDRA 14.0	EG0001 affected111 at risk EG0011 affected105 at risk
Chest pain	General disorders	MedDRA 14.0	EG0000 affected111 at risk EG0012 affected105 at risk
Pneumonia	Infections and infestations	MedDRA 14.0	EG0000 affected111 at risk EG0011 affected105 at risk
Joint sprain	Injury, poisoning and procedural complications	MedDRA 14.0	EG0001 affected111 at risk EG0010 affected105 at risk
Blood amylase increased	Investigations	MedDRA 14.0	EG0001 affected111 at risk EG0010 affected105 at risk
Lipase increased	Investigations	MedDRA 14.0	EG0001 affected111 at risk EG0010 affected105 at risk
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA 14.0	EG0001 affected111 at risk EG0010 affected105 at risk
Myositis	Musculoskeletal and connective tissue disorders	MedDRA 14.0	EG0001 affected111 at risk EG0010 affected105 at risk
Small cell lung cancer stage unspecified	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	EG0000 affected111 at risk EG0011 affected105 at risk
Renal injury	Renal and urinary disorders	MedDRA 14.0	EG0000 affected111 at risk EG0011 affected105 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 14.0	EG0000 affected111 at risk EG0011 affected105 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 14.0	EG00053 affected111 at risk EG00112 affected105 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 14.0	EG00019 affected111 at risk EG00111 affected105 at risk
Vomiting	Gastrointestinal disorders	MedDRA 14.0	EG00016 affected111 at risk EG0019 affected105 at risk
Constipation	Gastrointestinal disorders	MedDRA 14.0	EG00010 affected111 at risk EG0013 affected105 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 14.0	EG0007 affected111 at risk EG0011 affected105 at risk
Injection site nodule	General disorders	MedDRA 14.0	EG00022 affected111 at risk EG0010 affected105 at risk
Injection site pruritus	General disorders	MedDRA 14.0	EG00012 affected111 at risk EG0011 affected105 at risk
Malaise	General disorders	MedDRA 14.0	EG0006 affected111 at risk EG0012 affected105 at risk
Nasopharyngitis	Infections and infestations	MedDRA 14.0	EG00023 affected111 at risk EG00131 affected105 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 14.0	EG0005 affected111 at risk EG0016 affected105 at risk
Influenza	Infections and infestations	MedDRA 14.0	EG0002 affected111 at risk EG0016 affected105 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	EG0009 affected111 at risk EG0017 affected105 at risk
Musculoskeletal	Musculoskeletal and connective tissue disorders	MedDRA 14.0	EG0007 affected111 at risk EG0012 affected105 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 14.0	EG0006 affected111 at risk EG0013 affected105 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 14.0	EG0005 affected111 at risk EG0016 affected105 at risk
Headache	Nervous system disorders	MedDRA 14.0	EG00023 affected111 at risk EG00115 affected105 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	EG0007 affected111 at risk EG0019 affected105 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	EG0004 affected111 at risk EG0018 affected105 at risk

ID	Term
D003924	Diabetes Mellitus, Type 2
D003920	Diabetes Mellitus

ID	Term
D000069057	Insulin Detemir

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