Safety and Efficacy of Exenatide Once Weekly Injection Versus Metformin, Dipeptidyl Peptidase-4 Inhibitor, or Thiazolidinedione as Monotherapy in Drug-Naive Patients With Type 2 Diabetes (DURATION-4)

Type 2 Diabetes Mellitus Clinical Trial

Official title:

Safety and Efficacy of Exenatide Once Weekly Injection Versus Metformin, Dipeptidyl Peptidase-4 Inhibitor, or Thiazolidinedione as Monotherapy in Drug-Naive Patients With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00676338
• Other study ID #: H8O-MC-GWCH (DURATION - 4)
• Status: Completed
• Phase: Phase 3
• First received: May 9, 2008
• Last updated: March 20, 2015
• Start date: November 2008
• Est. completion date: January 2011

Study information

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

Clinical Trial Summary

This study will compare the effects of 2.0 mg exenatide once weekly injection as monotherapy to 3 active comparators(metformin, dipeptidyl peptidase-4 inhibitor, and thiazolidinedione) in drug naive patients with type 2 diabetes treated with diet and exercise.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 820
• Est. completion date: January 2011
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• have type 2 diabetes and are treated with diet and exercise alone.

• at least 18 years of age.

• HbA1c between 7.1% and 11.0%, inclusive.

• Body mass index (BMI) of 23 kg/m2 to 45 kg/m2, inclusive.

• Have a history of stable body weight (not varying by >5% for at least 3 months prior to screening).

Exclusion Criteria:

• Have 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

• 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 history of severe GI disorder (e.g., gastroparesis)

• Have a history of acute or chronic pancreatitis.

• 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 with any antidiabetic agent for more than 7 days within 3 months prior to screening.

• Have had an organ transplant.

• Have previously completed or discontinued study drug in this study, 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: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• exenatide once weekly
subcutaneous injection, 2mg, once weekly plus placebo oral once daily
• metformin
oral, 1000-2500mg, daily plus placebo once weekly subcutaneous injection
• sitagliptin
oral, 100 mg, daily plus placebo once weekly subcutaneous injection
• pioglitazone
oral, 30-45mg, daily plus placebo once weekly subcutaneous injection

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Mar del Plata
Belgium	Research Site	Leuven
Belgium	Research Site	Marchovelette
Belgium	Research Site	Tessenderlo
Brazil	Research Site	Brasilia
Brazil	Research Site	Campinas
Brazil	Research Site	Curitiba
Brazil	Research Site	Fortaleza
Brazil	Research Site	Joinville
Brazil	Research SIte	Porto Alegre
Brazil	Research Site	Recife
Brazil	Research Site	Sao Paolo
Canada	Research Site	Coquitlam	British Columbia
Canada	Research Site	Gatineu	Quebec
Canada	Research Site	Mississauga
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Penticton	British Columbia
Canada	Research Site	Petitcodiac
Canada	Research Site	Pointe-Claire
Canada	Research Site	Regina
Canada	Research Site	Saint John
France	Research Site	Chateaugiron
France	Research Site	Murs Erigne
France	Research Site	Nantes
France	Research Site	Vieux Conde
Germany	Research Site	Dresden
Germany	Research Site	Mainz
Germany	Research Site	Muenster
Germany	Research Site	Rodgau
Hungary	Research Site	Budapest
Hungary	Research Site	Gyula
Hungary	Research Site	Hodmezovasarhely
Hungary	Research Site	Pecs
India	Research Site	Ahmedabad
India	Research Site	Bangalore
India	Research Site	Channai
India	Research Site	Cochin
India	Research Site	Mumbai
India	Research Site	New Dehli
India	Research SIte	Pune
Israel	Research Site	Holon
Israel	Research SIte	Tel-Hashomer
Italy	Research Site	Firenze
Italy	Research Site	Milano
Italy	Research Site	Siena
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Jeonju
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Sungnam
Mexico	Research Site	Chihuahua
Mexico	Research Site	Guadalajara
Mexico	Research Site	Monterrey
Poland	Research Site	Lublin
Poland	Research Site	Szczecin
Poland	Research Site	Wroclaw
Puerto Rico	Research Site	Manati
Puerto Rico	Research Site	Toa Baja
Romania	Research Site	Galati
Romania	Research Site	Oradea
Romania	Research Site	Targu Mures
Russian Federation	Research Site	Arkhangelsk
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Rostov-on-Don
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Stavropol
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Trebisov
South Africa	Research Site	Johannesburg
South Africa	Research Site	Kempton Park
South Africa	Research Site	Midrand
South Africa	Research Site	Soweto
Spain	Research Site	Alicante
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Sevilla
Turkey	Research Site	Ankara
Turkey	Research Site	Istanbul
Turkey	Research Site	Sisli-Istanbul
United Kingdom	Research Site	Bath
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	Frome
United Kingdom	Research Site	Guildford
United Kingdom	Research Site	Hull
United Kingdom	Research Site	Sheffield
United Kingdom	Research Site	Swansea
United States	Research Site	Atlanta	Georgia
United States	Research Site	Austin	Texas
United States	Research Site	Billings	Montana
United States	Research Site	Buena Park	California
United States	Research Site	Danville	Pennsylvania
United States	Research Site	Des Moines	Iowa
United States	Research Site	El Paso	Texas
United States	Research Site	Grand Rapids	Michigan
United States	Research Site	Jacksonville	Florida
United States	Research Site	Los Angeles	California
United States	Research Site	Meridian	Idaho
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	New Branufels	Texas
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Toms River	New Jersey
United States	Research Site	Valencia	California
United States	Research Site	Wilke Barre	Pennsylvania
United States	Research Site	Wilmington	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  France,  Germany,  Hungary,  India,  Israel,  Italy,  Korea, Republic of,  Mexico,  Poland,  Puerto Rico,  Romania,  Russian Federation,  Slovakia,  South Africa,  Spain,  Turkey,  United Kingdom, 

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
Primary	Percentage of Patients Achieving HbA1c <=7% at Week 26	Percentage of patients achieving HbA1c <=7% at Week 26 (for patients with baseline HbA1c >7%).	Baseline, Week 26	No
Secondary	Change in Fasting Serum Glucose (FSG) From Baseline to Week 26	Change in FSG from baseline to Week 26.	Baseline, Week 26	No
Secondary	Change in Body Weight From Baseline to Week 26	Change in Body Weight from baseline to Week 26.	Baseline, Week 26	No
Secondary	Change in Fasting Total Cholesterol (TC) From Baseline to Week 26	Change in Fasting TC from baseline to Week 26.	Baseline, Week 26	No
Secondary	Change in Fasting High-Density Lipoprotein (HDL) From Baseline to Week 26	Change in Fasting HDL from baseline to Week 26.	Baseline, Week 26	No
Secondary	Ratio of Fasting Triglycerides at Week 26 to Baseline	Ratio of Fasting Triglycerides (measured in mmol/L) at Week 26 to baseline. Log(Post-baseline Triglycerides) - log(Baseline Triglycerides); change from baseline to Week 26 is presented as ratio of endpoint to baseline.	Baseline, Week 26	No
Secondary	Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events	Major hypoglycemia is defined as any event that has symptoms consistent with hypoglycemia resulting in loss of consciousness or seizure that shows prompt recovery in response to administration of glucagon or glucose, or documented hypoglycemia (blood glucose <3.0 mmol/L [54 mg/dL]) requiring the assistance of another person because of severe impairment in consciousness or behavior (whether or not symptoms of hypoglycemia are detected by the patient). Mean event rate = total number of events for all subjects in a treatment regimen / the total number of subject years of exposure for all subjects in that treatment. Standard error = square root of (total number of events / (subject years of exposure)**2).	Baseline to Week 26	Yes
Secondary	Assessment on Event Rate of Treatment-Emergent Minor Hypoglycemic Events	Minor hypoglycemia is defined as a sign or symptom associated with hypoglycemia that is either self-treated by the patient or resolves on its own AND has a concurrent finger stick blood glucose <3.0 mmol/L (54 mg/dL) and not classified as major hypoglycemia. Mean event rate = total number of events for all subjects in a treatment regimen / the total number of subject years of exposure for all subjects in that treatment. Standard error = square root of (total number of events / (subject years of exposure)**2).	Baseline to Week 26	Yes
Secondary	Change in Systolic Blood Pressure From Baseline to Week 26.	Change in Systolic Blood Pressure from baseline to Week 26.	Baseline, Week 26	Yes
Secondary	Change in Diastolic Blood Pressure From Baseline to Week 26.	Change in Diastolic Blood Pressure from baseline to Week 26.	Baseline, Week 26	Yes