Clinical trial NCT00641056: Efficacy of Exenatide Once Weekly and Once-Daily Insulin Glargine in Patients With Type 2 Diabetes Treated With Metformin Alone or in Combination With Sulfonylurea (DURATION - 3)
Official title: Efficacy of Once-Weekly Exenatide Long-Acting Release and Once-Daily Insulin Glargine in Patients With Type 2 Diabetes Treated With Metformin Alone or in Combination With Sulfonylurea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Keywords: diabetes
exenatide
exenatide once weekly
metformin
sulfonylurea
insulin glargine
Amylin
Lilly
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2008-03-21
Enrollment: 467
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: The purpose of this study is to compare the effects of 2.0 mg exenatide once weekly and insulin glargine, titrated to glucose targets using the algorithm described by Yki- Järvinen et al.(2007), with respect to glycemic improvements, body weight, fasting lipids, safety, and tolerability.


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.

Primary outcomes:
measure: Change in HbA1c From Baseline to Week 26
timeFrame: Baseline, Week 26
Secondary outcomes:
measure: Percentage of Patients Achieving HbA1c <=7.0% at Week 26
timeFrame: Baseline, Week 26
measure: Percentage of Patients Achieving HbA1c <=6.5% at Week 26
timeFrame: Baseline, Week 26
measure: Change in Fasting Serum Glucose (FSG) From Baseline to Week 26
timeFrame: Baseline, Week 26
measure: Change in Body Weight (BW) From Baseline to Week 26
timeFrame: Baseline, Week 26
measure: Change in Total Cholesterol From Baseline to Week 26
timeFrame: Baseline, Week 26
measure: Change in High-density Lipoprotein Cholesterol (HDL) From Baseline to Week 26
timeFrame: Baseline, Week 26
measure: Ratio of Triglycerides at Week 26 to Baseline
timeFrame: Baseline, Week 26
measure: Change in Blood Pressure From Baseline to Week 26
timeFrame: Baseline, Week 26
measure: Assessment on Event Rate of Treatment-emergent Hypoglycemic Episodes
timeFrame: Baseline to Week 26
Other outcomes:
Locations:
city: Escondido
country: United States
facility: Research Site
state: California
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: West Palm Beach
country: United States
facility: Research Site
state: Florida
city: Honolulu
country: United States
facility: Research Site
state: Hawaii
city: Idaho Falls
country: United States
facility: Research Site
state: Idaho
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: St. Louis
country: United States
facility: Research Site
state: Missouri
city: Dayton
country: United States
facility: Research Site
state: Ohio
city: Ada
country: United States
facility: Research Site
state: Oklahoma
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Spokane
country: United States
facility: Research Site
state: Washington
city: Wollongong
country: Australia
facility: Research Site
state: New South Wales
city: Herston
country: Australia
facility: Research Site
state: Queensland
city: Adelaide
country: Australia
facility: Research Site
state: South Australia
city: Keswick
country: Australia
facility: Research Site
state: South Australia
city: Box Hill
country: Australia
facility: Research Site
state: Victoria
city: Geelong
country: Australia
facility: Research Site
state: Victoria
city: Brussels
country: Belgium
facility: Research Site
city: Edegem
country: Belgium
facility: Research Site
city: Melnik
country: Czech Republic
facility: Research Site
city: Praha
country: Czech Republic
facility: Research Site
city: Stodulky
country: Czech Republic
facility: Research Site
city: Aalborg
country: Denmark
facility: Research Site
city: Arhus C
country: Denmark
facility: Research Site
city: Herlev
country: Denmark
facility: Research Site
city: Koge
country: Denmark
facility: Research Site
city: Angers
country: France
facility: Research Site
city: Corbeil Essoness
country: France
facility: Research Site
city: Nancy
country: France
facility: Research Site
city: Nanterre
country: France
facility: Research Site
city: Toulouse
country: France
facility: Research Site
city: Bad Mergentheim
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Falkensee
country: Germany
facility: Research Site
city: Fulda
country: Germany
facility: Research Site
city: Hamburg-Othmarschen
country: Germany
facility: Research Site
city: Munster
country: Germany
facility: Research Site
city: Rothenburg an der fulda
country: Germany
facility: Research Site
city: Speyer
country: Germany
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Eger
country: Hungary
facility: Research Site
city: Gyula
country: Hungary
facility: Research Site
city: Pecs
country: Hungary
facility: Research Site
city: Gyeonggi-Do
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Merida
country: Mexico
facility: Research Site
city: Mexico City
country: Mexico
facility: Research Site
city: Tampico
country: Mexico
facility: Research Site
city: Tijuana
country: Mexico
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Gouda
country: Netherlands
facility: Research Site
city: Hoogeveen
country: Netherlands
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Research Site
city: Zwijndrecht
country: Netherlands
facility: Research Site
city: Zwolle
country: Netherlands
facility: Research Site
city: Caguas
country: Puerto Rico
facility: Research Site
city: Yabucoa
country: Puerto Rico
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Rostov-on-Don
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Alicante
country: Spain
facility: Research Site
city: Alzira-Valencia
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Bilbao
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Teruel
country: Spain
facility: Research Site
city: Chia-Yi
country: Taiwan
facility: Research Site
city: Tainan County
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
Study officials:
affiliation: Eli Lilly and Company
name: Chief Medical Officer, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: Diamant M, Van Gaal L, Guerci B, Stranks S, Han J, Malloy J, Boardman MK, Trautmann ME. Exenatide once weekly versus insulin glargine for type 2 diabetes (DURATION-3): 3-year results of an open-label randomised trial. Lancet Diabetes Endocrinol. 2014 Jun;2(6):464-73. doi: 10.1016/S2213-8587(14)70029-4. Epub 2014 Apr 4.
citation: Grimm M, Han J, Weaver C, Griffin P, Schulteis CT, Dong H, Malloy J. Efficacy, safety, and tolerability of exenatide once weekly in patients with type 2 diabetes mellitus: an integrated analysis of the DURATION trials. Postgrad Med. 2013 May;125(3):47-57. doi: 10.3810/pgm.2013.05.2660.
citation: Meloni AR, DeYoung MB, Han J, Best JH, Grimm M. Treatment of patients with type 2 diabetes with exenatide once weekly versus oral glucose-lowering medications or insulin glargine: achievement of glycemic and cardiovascular goals. Cardiovasc Diabetol. 2013 Mar 23;12:48. doi: 10.1186/1475-2840-12-48.
citation: Fineman MS, Mace KF, Diamant M, Darsow T, Cirincione BB, Booker Porter TK, Kinninger LA, Trautmann ME. Clinical relevance of anti-exenatide antibodies: safety, efficacy and cross-reactivity with long-term treatment. Diabetes Obes Metab. 2012 Jun;14(6):546-54. doi: 10.1111/j.1463-1326.2012.01561.x. Epub 2012 Feb 10.
citation: Diamant M, Van Gaal L, Stranks S, Northrup J, Cao D, Taylor K, Trautmann M. Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial. Lancet. 2010 Jun 26;375(9733):2234-43. doi: 10.1016/S0140-6736(10)60406-0.