Phase III Study to Evaluate Safety and Efficacy of Added... | NCT02229383

ID	Type	Description	Link
2014-003502-33	EudraCT Number

Official Title

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Once Weekly Exenatide Therapy Added to Titrated Basal Insulin Glargine Compared to Placebo Added to Titrated Basal Insulin Glargine in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Basal Insulin Glargine With or Without Metformin

Status Module

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Exenatide	Experimental	Exenatide 2 mg 1 time per week + titrated basal insulin glargine with or without metformin	Drug: Exenatide
Placebo	Placebo Comparator	Placebo 2 mg 1 time per week + titrated basal insulin glargine with or without metformin	Drug: Exenatide matching placebo

Name	Type	Description	Arm Group Labels	Other Names
Exenatide	Drug	2 mg weekly suspension injection	Exenatide
Exenatide matching placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in HbA1c From Baseline to Week 28	To compare the change from baseline in HbA1c achieved with exenatide once weekly (EQW) added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment. SU= sulfonylurea.	Baseline to Week 28

Secondary Outcomes

Measure	Description	Time Frame
Change in Body Weight From Baseline to Week 28	To compare the change from baseline in body weight achieved with EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment.	Baseline to Week 28
Change From Baseline to Week 28 in 2-hour Postprandial Glucose After a Standard Meal Tolerance Test (MTT)

Eligibility Module

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Birmingham	Alabama	35235	United States
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.
29473704	Derived	Guja C, Frias JP, Somogyi A, Jabbour S, Wang H, Hardy E, Rosenstock J. Effect of exenatide QW or placebo, both added to titrated insulin glargine, in uncontrolled type 2 diabetes: The DURATION-7 randomized study. Diabetes Obes Metab. 2018 Jul;20(7):1602-1614. doi: 10.1111/dom.13266. Epub 2018 Mar 25.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Exenatide	Exenatide 2 milligram (mg) 1 time per week + titrated basal insulin glargine with or without metformin.
FG001	Placebo	Placebo (matching with exenatide) 1 time per week + titrated basal insulin glargine with or without metformin.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Exenatide	Exenatide 2 mg 1 time per week + titrated basal insulin glargine with or without metformin.
BG001	Placebo	Placebo (matching with exenatide) 1 time per week + titrated basal insulin glargine with or without metformin.
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, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00057.8± 9.04 BG00157.5± 10.28 BG00257.7± 9.67

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000117 BG001122 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian Or Alaska Native	BG0001 BG0010 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 28

To compare the change from baseline in HbA1c achieved with exenatide once weekly (EQW) added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment. SU= sulfonylurea.

The ITT analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment. Only participants with data available for analysis are presented.

Posted

Least Squares Mean

95% Confidence Interval

Percentage of HbA1c

Baseline to Week 28

ID	Title	Description
OG000	Exenatide	Exenatide 2 mg 1 time per week + titrated basal insulin glargine with or without metformin.
OG001	Placebo	Placebo (matching with exenatide) 1 time per week + titrated basal insulin glargine with or without metformin.

Units	Counts
Participants	OG000230 OG001228

Title

Denominators

Categories

Title	Measurements
	OG000-0.96(-1.12 to -0.81) OG001-0.22(-0.38 to -0.07)

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 Models Analysis	Treatment, region, baseline HbA1c (< or ≥ 9.0%), baseline SU-use, week, treatment by week interaction as fixed factors; baseline value as covariate.	<0.001		Mean Difference (Final Values)	-0.74	Standard Error of the Mean	0.101	2-Sided	95	-0.94	-0.54					Superiority or Other

Secondary

Change in Body Weight From Baseline to Week 28

To compare the change from baseline in body weight achieved with EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment.

Posted

Least Squares Mean

95% Confidence Interval

kilogram

Baseline to Week 28

ID	Title	Description
OG000	Exenatide	Exenatide 2 mg 1 time per week + titrated basal insulin glargine with or without metformin.
OG001	Placebo	Placebo (matching with exenatide) 1 time per week + titrated basal insulin glargine with or without metformin.

Units	Counts
Participants	OG000

Secondary

Change From Baseline to Week 28 in 2-hour Postprandial Glucose After a Standard Meal Tolerance Test (MTT)

To compare the change from baseline in 2-hour postprandial glucose after a standard MTT achieved with EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment.

Posted

Least Squares Mean

95% Confidence Interval

milligram per deciliter

Baseline to Week 28

ID	Title	Description
OG000	Exenatide	Exenatide 2 mg 1 time per week + titrated basal insulin glargine with or without metformin.
OG001	Placebo	Placebo (matching with exenatide) 1 time per week + titrated basal insulin glargine with or without metformin.

Units	Counts
Participants

Secondary

Percentage of Participants Achieving HbA1c <7.0% at Week 28

To compare the percentage of participants achieving HbA1c <7.0% between EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment.

The ITT analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment.

Posted

Number

95% Confidence Interval

Percentage of participants

Baseline to Week 28

ID	Title	Description
OG000	Exenatide	Exenatide 2 mg 1 time per week + titrated basal insulin glargine with or without metformin.
OG001	Placebo	Placebo (matching with exenatide) 1 time per week + titrated basal insulin glargine with or without metformin.

Units	Counts
Participants	OG000

Secondary

Change From Baseline to Week 28 in Daily Insulin Dose

To compare the change from baseline in daily insulin dose achieved with EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment.

Posted

Least Squares Mean

95% Confidence Interval

Units

Baseline to Week 28

ID	Title	Description
OG000	Exenatide	Exenatide 2 mg 1 time per week + titrated basal insulin glargine with or without metformin.
OG001	Placebo	Placebo (matching with exenatide) 1 time per week + titrated basal insulin glargine with or without metformin.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Achieving HbA1c <7.0% at Week 28, No Weight Gain at Week 28, and No Major Hypoglycemia Over 28 Weeks

To compare the percentage of participants achieving HbA1c <7.0% at Week 28, no weight gain at Week 28, and no major hypoglycemia over 28 weeks between EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin.

The ITT analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment.

Posted

Number

95% Confidence Interval

Percentage of participants

Baseline to Week 28

ID	Title	Description
OG000	Exenatide	Exenatide 2 mg 1 time per week + titrated basal insulin glargine with or without metformin.
OG001	Placebo	Placebo (matching with exenatide) 1 time per week + titrated basal insulin glargine with or without metformin.

Units	Counts
Participants

Secondary

Change in Seated Systolic Blood Pressure From Baseline to Week 28

To compare the change from baseline in seated systolic blood pressure achieved with EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment.

Posted

Least Squares Mean

95% Confidence Interval

millimeter of mercury

Baseline to Week 28

ID	Title	Description
OG000	Exenatide	Exenatide 2 mg 1 time per week + titrated basal insulin glargine with or without metformin.
OG001	Placebo	Placebo (matching with exenatide) 1 time per week + titrated basal insulin glargine with or without metformin.

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	Exenatide 2 mg 1 time per week + titrated basal insulin glargine with or without metformin.	0	231	11	231	40	231
EG001	Placebo	Placebo (matching with exenatide) 1 time per week + titrated basal insulin glargine with or without metformin.	1	229	11	229	36	229

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Angina unstable	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected231 at risk EG0011 events1 affected229 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected231 at risk EG0012 events2 affected229 at risk
Coronary artery disease	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected231 at risk EG0011 events1 affected229 at risk
Coronary artery stenosis	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected231 at risk EG0010 events0 affected229 at risk
Myocardial infarction	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected231 at risk EG0011 events1 affected229 at risk
Abdominal mass	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected231 at risk EG0010 events0 affected229 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected231 at risk EG0010 events0 affected229 at risk
Large intestine polyp	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected231 at risk EG0010 events0 affected229 at risk
Chest pain	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected231 at risk EG0010 events0 affected229 at risk
Appendicitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected231 at risk EG0011 events1 affected229 at risk
Cellulitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected231 at risk EG0011 events1 affected229 at risk
Diverticulitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected231 at risk EG0011 events1 affected229 at risk
Osteomyelitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected231 at risk EG0010 events0 affected229 at risk
Pneumonia	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected231 at risk EG0011 events1 affected229 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected231 at risk EG0010 events0 affected229 at risk
Toxicity to various agents	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected231 at risk EG0010 events0 affected229 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected231 at risk EG0012 events2 affected229 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected231 at risk EG0010 events0 affected229 at risk
Carpal tunnel syndrome	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected231 at risk EG0011 events1 affected229 at risk
Headache	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected231 at risk EG0011 events1 affected229 at risk
Neuralgia	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected231 at risk EG0011 events1 affected229 at risk
Acute stress disorder	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected231 at risk EG0010 events0 affected229 at risk
Alcohol withdrawal syndrome	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected231 at risk EG0010 events0 affected229 at risk
Depression	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected231 at risk EG0010 events0 affected229 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected231 at risk EG0010 events0 affected229 at risk
Bladder neck obstruction	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected231 at risk EG0011 events1 affected229 at risk
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected231 at risk EG0010 events0 affected229 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG00013 events12 affected231 at risk EG00110 events9 affected229 at risk
Injection site nodule	General disorders	MedDRA 19.0	Systematic Assessment	EG00014 events12 affected231 at risk EG0011 events1 affected229 at risk
Urinary tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG00025 events18 affected231 at risk EG00121 events15 affected229 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0006 events5 affected231 at risk EG00115 events13 affected229 at risk

Certain Agreements

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