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)

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00641056
• Other study ID #: H8O-MC-GWBR (DURATION - 3)
• Status: Completed
• Phase: Phase 3
• First received: March 17, 2008
• Last updated: May 21, 2015
• Start date: April 2008
• Est. completion date: November 2009

Study information

• Verified date: May 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 467
• Est. completion date: November 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Exenatide Once Weekly
subcutaneous injection, 2.0mcg, once weekly
• Insulin Glargine
subcutaneous injection, variable dose, QD

Locations

Country	Name	City	State
Australia	Research Site	Adelaide	South Australia
Australia	Research Site	Box Hill	Victoria
Australia	Research Site	Geelong	Victoria
Australia	Research Site	Herston	Queensland
Australia	Research Site	Keswick	South Australia
Australia	Research Site	Wollongong	New South Wales
Belgium	Research Site	Brussels
Belgium	Research Site	Edegem
Czech Republic	Research Site	Melnik
Czech Republic	Research Site	Praha
Czech Republic	Research Site	Stodulky
Denmark	Research Site	Aalborg
Denmark	Research Site	Arhus C
Denmark	Research Site	Herlev
Denmark	Research Site	Koge
France	Research Site	Angers
France	Research Site	Corbeil Essoness
France	Research Site	Nancy
France	Research Site	Nanterre
France	Research Site	Toulouse
Germany	Research Site	Bad Mergentheim
Germany	Research Site	Dresden
Germany	Research Site	Essen
Germany	Research Site	Falkensee
Germany	Research Site	Fulda
Germany	Research Site	Hamburg-Othmarschen
Germany	Research Site	Munster
Germany	Research Site	Rothenburg an der fulda
Germany	Research Site	Speyer
Greece	Research Site	Athens
Greece	Research Site	Thessaloniki
Hungary	Research Site	Budapest
Hungary	Research Site	Eger
Hungary	Research Site	Gyula
Hungary	Research Site	Pecs
Korea, Republic of	Research Site	Gyeonggi-Do
Korea, Republic of	Research Site	Seoul
Mexico	Research Site	Merida
Mexico	Research Site	Mexico City
Mexico	Research Site	Tampico
Mexico	Research Site	Tijuana
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Gouda
Netherlands	Research Site	Hoogeveen
Netherlands	Research Site	Rotterdam
Netherlands	Research Site	Zwijndrecht
Netherlands	Research Site	Zwolle
Puerto Rico	Research Site	Caguas
Puerto Rico	Research Site	Yabucoa
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Rostov-on-Don
Russian Federation	Research Site	St. Petersburg
Spain	Research Site	Alicante
Spain	Research Site	Alzira-Valencia
Spain	Research Site	Barcelona
Spain	Research Site	Bilbao
Spain	Research Site	Madrid
Spain	Research Site	Malaga
Spain	Research Site	Teruel
Taiwan	Research Site	Chia-Yi
Taiwan	Research Site	Tainan County
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan
United States	Research Site	Ada	Oklahoma
United States	Research Site	Dayton	Ohio
United States	Research Site	Escondido	California
United States	Research Site	Honolulu	Hawaii
United States	Research Site	Idaho Falls	Idaho
United States	Research Site	Jacksonville	Florida
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Orlando	Florida
United States	Research Site	San Antonio	Texas
United States	Research Site	Spokane	Washington
United States	Research Site	St. Louis	Missouri
United States	Research Site	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Czech Republic,  Denmark,  France,  Germany,  Greece,  Hungary,  Korea, Republic of,  Mexico,  Netherlands,  Puerto Rico,  Russian Federation,  Spain,  Taiwan, 

References & Publications (1)

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. 201 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c From Baseline to Week 26	Change in HbA1c from baseline to Week 26	Baseline, Week 26	No
Secondary	Percentage of Patients Achieving HbA1c <=7.0% at Week 26	Percentage of patients achieving HbA1c <=7.0% at Week 26 (for patients with HbA1c >7% at baseline)	Baseline, Week 26	No
Secondary	Percentage of Patients Achieving HbA1c <=6.5% at Week 26	Percentage of patients achieving HbA1c <=6.5% at Week 26 (for patients with HbA1c >6.5% at baseline)	Baseline, Week 26	No
Secondary	Change in Fasting Serum Glucose (FSG) From Baseline to Week 26	Change in FSG (mmol/L) from Baseline to Week 26	Baseline, Week 26	No
Secondary	Change in Body Weight (BW) From Baseline to Week 26	Change in BW (kg) from Baseline to Week 26	Baseline, Week 26	No
Secondary	Change in Total Cholesterol From Baseline to Week 26	Change in Total Cholesterol (mmol/L) from Baseline to Week 26	Baseline, Week 26	No
Secondary	Change in High-density Lipoprotein Cholesterol (HDL) From Baseline to Week 26	Change in HDL (mmol/L) from Baseline to Week 26	Baseline, Week 26	No
Secondary	Ratio of Triglycerides at Week 26 to Baseline	Ratio of Triglycerides (measured in mmol/L) at Week 26 to Baseline. Log (Postbaseline Triglycerides) - log (Baseline Triglycerides); change from baseline to endpoint is presented as ratio of endpoint to baseline.	Baseline, Week 26	No
Secondary	Change in Blood Pressure From Baseline to Week 26	Change in Systolic Blood Pressure (mmHg) and Diastolic Blood Pressure (mmHg) from Baseline to Week 26	Baseline, Week 26	No
Secondary	Assessment on Event Rate of Treatment-emergent Hypoglycemic Episodes	Major hypoglycemia: any episode with symptoms consistent with hypoglycemia that resulted in loss of consciousness or seizure with prompt recovery in response to administration of glucagon or glucose or documented hypoglycemia (blood glucose <3.0 mmol/L [54 mg/dL]) and required the assistance of another person. Minor hypoglycemia: any time a patient felt that he or she was experiencing a sign or symptom of hypoglycemia that was self-treated or resolved on its own and had a blood glucose level <3.0 mmol/L (54 mg/dL) and not classified as major hypoglycemia.	Baseline to Week 26	Yes