Clinical trial NCT00765817: Addition Of Exenatide To Insulin Glargine In Type 2 Diabetes Mellitus
Official title: A Randomized Trial Comparing Exenatide With Placebo in Subjects With Type 2 Diabetes on Insulin Glargine With or Without Oral Antihyperglycemic Medications
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes
Keywords: diabetes
exenatide
Amylin
Lilly
metformin
pioglitazone
insulin glargine
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2008-10-03
Enrollment: 261
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will compare the efficacy and safety of exenatide versus placebo in adults whose diabetes is not fully controlled by insulin glargine with or without metformin and/or pioglitazone.


Eligibility criteria: Inclusion Criteria:

* Have type 2 diabetes.
* Have been taking insulin glargine at a dose of ≥20 units/day for at least 3 months before entering the study.

Have been taking insulin glargine alone or in combination with one of the following for at least 3 months before entering the study:

1. metformin (stable dose for 6 weeks)
2. pioglitazone (stable dose for 6 weeks)
3. a combination of metformin and pioglitazone (stable dose for 6 weeks)

   * Have HbA1C between 7.1% and 10.5%, inclusive.
   * Have a body mass index (BMI) ≤45 kg/m2.
   * Have a history of stable body weight (not varying by \>5% for at least 3 months prior to screening).

Exclusion Criteria:

* Have taken medications to lower blood sugar other than insulin glargine, pioglitazone, or metformin in the 3 months before entering the study for more than a 1-week period, or within 1 week of entering the study.
* Have had more than one episode of major (severe) hypoglycemia in the 6 months before entering the study.
* Are pregnant or intend to become pregnant during the study or are sexually active women not actively practicing birth control.
* Women who are breastfeeding.
* Have any significant diseases of the blood, heart, kidney, gastrointestinal system, or other significant diseases such as cancer.
* Have had a kidney transplant or are currently on kidney dialysis.
* Have a cancer that's never been treated, that's currently being treated, or that was diagnosed within the last 5 years.
* Have had a bad reaction to exenatide in the past or have a condition that is not recommended to be exposed to exenatide or any of exenatide's other ingredients.
* Have used a drug for weight loss in the 3 months before entering the study for more than a 1-week period, or within 1 month of entering the study.
* Are currently on a weight-loss program or have been on one within 3 months of entering the study.
* Have had a blood transfusion or severe blood loss within 3 months of entering the study.
* Are taking systemic glucocorticoids or have received systemic glucocorticoids within 8 weeks of entering the study.
* Have an irregular sleep cycle (for example, sleeping during the day and working during the night).
* Have a history of pancreatitis.
* Have received treatment with an experimental drug within 30 days of entering the study.
* If on metformin, have a condition that is not recommended to be exposed to metformin, or any condition associated with hypoperfusion, hypoxemia, dehydration, or sepsis.
* If on metformin, have had a radiologic contrast study performed within 48 hours of entering the study.
* If on pioglitazone, have a condition that is not recommended to be exposed to pioglitazone, including congestive heart failure, or are taking pioglitazone at a dose that is not approved for use with insulin.

Primary outcomes:
measure: Change in Glycosylated Hemoglobin (HbA1c)
timeFrame: baseline and 30 weeks
Secondary outcomes:
measure: Percentage of Patients Achieving HbA1c <=7%
timeFrame: baseline and 30 weeks
measure: Percentage of Patients Achieving HbA1c <=6.5%
timeFrame: baseline and 30 weeks
measure: Change in Fasting Serum Glucose
timeFrame: baseline and 30 weeks
measure: Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
timeFrame: baseline and 30 weeks
measure: Change in Total Cholesterol
timeFrame: baseline and 30 weeks
measure: Change in Low Density Lipoprotein (LDL) Cholesterol
timeFrame: baseline and 30 weeks
measure: Change in High Density Lipoprotein (HDL) Cholesterol
timeFrame: baseline and 30 weeks
measure: Change in Triglycerides
timeFrame: baseline and 30 weeks
measure: Change in Body Weight
timeFrame: baseline and 30 weeks
measure: Change in Waist Circumference
timeFrame: baseline and 30 weeks
measure: Change in Daily Insulin Dose
timeFrame: baseline and 30 weeks
measure: Change in Daily Insulin Dose (on a Per Body Weight Basis)
timeFrame: baseline and 30 weeks
measure: Change in Systolic Blood Pressure (SBP)
timeFrame: baseline and 30 weeks
measure: Change in Diastolic Blood Pressure (DBP)
timeFrame: baseline and 30 weeks
measure: Minor Hypoglycemia Rate Per Year
timeFrame: baseline and weeks 2, 4, 6, 8, 10, 14, 18, 22, 26, and 30
measure: Percentage of Subjects Experiencing Minor Hypoglycemia
timeFrame: baseline and weeks 2, 4, 6, 8, 10, 14, 18, 22, 26, and 30
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Research Site
state: Arizona
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Buena Park
country: United States
facility: Research Site
state: California
city: Concord
country: United States
facility: Research Site
state: California
city: Fresno
country: United States
facility: Research Site
state: California
city: Greenbrae
country: United States
facility: Research Site
state: California
city: La Mesa
country: United States
facility: Research Site
state: California
city: Lancaster
country: United States
facility: Research Site
state: California
city: Northridge
country: United States
facility: Research Site
state: California
city: Palm Springs
country: United States
facility: Research Site
state: California
city: Salinas
country: United States
facility: Research Site
state: California
city: Hollywood
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Honolulu
country: United States
facility: Research Site
state: Hawaii
city: Idaho Falls
country: United States
facility: Research Site
state: Idaho
city: Des Moines
country: United States
facility: Research Site
state: Iowa
city: Wichita
country: United States
facility: Research Site
state: Kansas
city: Baton Rouge
country: United States
facility: Research Site
state: Louisiana
city: Lafayette
country: United States
facility: Research Site
state: Louisiana
city: Matairie
country: United States
facility: Research Site
state: Louisiana
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Chesterfield
country: United States
facility: Research Site
state: Missouri
city: St Louis
country: United States
facility: Research Site
state: Missouri
city: Omaha
country: United States
facility: Research Site
state: Nebraska
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Berkeley Heights
country: United States
facility: Research Site
state: New Jersey
city: Teaneck
country: United States
facility: Research SIte
state: New Jersey
city: Alburquerque
country: United States
facility: Research Site
state: New Mexico
city: New York
country: United States
facility: Research SIte
state: New York
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Bend
country: United States
facility: Research Site
state: Oregon
city: Dallas
country: United States
facility: Research Site
state: Texas
city: El Paso
country: United States
facility: Research Site
state: Texas
city: Georgetown
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Richmond
country: United States
facility: Research Site
state: Virginia
city: Vancouver
country: United States
facility: Research Site
state: Washington
city: Kenosha
country: United States
facility: Research Site
state: Wisconsin
city: Athens
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: Holon
country: Israel
facility: Research Site
city: Kfar Sava
country: Israel
facility: Research Site
city: Tel Hashomer
country: Israel
facility: Research Site
city: Coatzacoalcos
country: Mexico
facility: Research Site
city: Mexico
country: Mexico
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
city: Carolina
country: Puerto Rico
facility: Research Site
city: Hato Rey
country: Puerto Rico
facility: Research Site
city: Ponce
country: Puerto Rico
facility: Research Site
city: San Juan
country: Puerto Rico
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Guildford
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: Livingston
country: United Kingdom
facility: Research Site
city: Middlesbrough
country: United Kingdom
facility: Research Site
city: Swansea
country: United Kingdom
facility: Research Site
city: Torquay
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Buse JB, Han J, Miller S, MacConell L, Pencek R, Wintle M. Addition of exenatide BID to insulin glargine: a post-hoc analysis of the effect on glycemia and weight across a range of insulin titration. Curr Med Res Opin. 2014 Jul;30(7):1209-18. doi: 10.1185/03007995.2014.896329. Epub 2014 Mar 18.
citation: Zinman B, Philis-Tsimikas A, Cariou B, Handelsman Y, Rodbard HW, Johansen T, Endahl L, Mathieu C; NN1250-3579 (BEGIN Once Long) Trial Investigators. Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes: a 1-year, randomized, treat-to-target trial (BEGIN Once Long). Diabetes Care. 2012 Dec;35(12):2464-71. doi: 10.2337/dc12-1205. Epub 2012 Oct 5.
citation: Pencek R, Blickensderfer A, Li Y, Brunell SC, Anderson PW. Exenatide twice daily: analysis of effectiveness and safety data stratified by age, sex, race, duration of diabetes, and body mass index. Postgrad Med. 2012 Jul;124(4):21-32. doi: 10.3810/pgm.2012.07.2567.
citation: Rosenstock J, Shenouda SK, Bergenstal RM, Buse JB, Glass LC, Heilmann CR, Kwan AY, MacConell LA, Hoogwerf BJ. Baseline factors associated with glycemic control and weight loss when exenatide twice daily is added to optimized insulin glargine in patients with type 2 diabetes. Diabetes Care. 2012 May;35(5):955-8. doi: 10.2337/dc11-1434. Epub 2012 Mar 19.
citation: Buse JB, Bergenstal RM, Glass LC, Heilmann CR, Lewis MS, Kwan AY, Hoogwerf BJ, Rosenstock J. Use of twice-daily exenatide in Basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial. Ann Intern Med. 2011 Jan 18;154(2):103-12. doi: 10.7326/0003-4819-154-2-201101180-00300. Epub 2010 Dec 6.