Safety and Efficacy of Exenatide Once Weekly Versus Liraglutide in Subjects With Type 2 Diabetes

Type 2 Diabetes Mellitus Clinical Trial

Official title:

Safety and Efficacy of Exenatide Once Weekly Versus Liraglutide in Subjects With Type 2 Diabetes and Inadequate Glycemic Control Treated With Lifestyle Modification and Oral Antidiabetic Medications

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01029886
• Other study ID #: H8O-MC-GWDE
• Status: Completed
• Phase: Phase 3
• First received: December 8, 2009
• Last updated: March 20, 2015
• Start date: January 2010
• Est. completion date: April 2011

Study information

• Verified date: March 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaAustralia: Therapeutic Goods Administration (TGA)Austria: Agency for Health and Food Safety, Federal Office for Safety in Health CareBelgium: Federal Agency for Medicines and Health Products, FAMHPCanada: Health CanadaCzech Republic: State Institute for Drug ControlFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesGreece: National Organization for MedicinesHungary: National Institute of PharmacyIndia: Ministry of Health: Drug Control General of India (DCGI)Israel: Israeli Health Ministry Pharmaceutical AdministrationItaly: The Italian Medicines AgencyMexico: National Institute of Public Health, Health SecretariatPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRomania: National Medicines AgencySlovakia: State Institute for Drug ControlSouth Africa: Medicines Control CouncilSouth Korea: Korea Food and Drug Administration (KFDA)Spain: Agencia Española del Medicamento y Productos SanitariosTaiwan: Department of Health
• Study type: Interventional

Clinical Trial Summary

No head to head comparisons between exenatide once weekly and liraglutide have been performed. Therefore, the purpose of this study is to compare exenatide once weekly to once-daily liraglutide with regard to HbA1c, body weight, subject-reported outcomes, and other clinical benefits. The study includes a 26-week treatment period and a safety follow-up visit 10 weeks after the final study drug dose.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 912
• Est. completion date: April 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosed with type 2 diabetes

• Have suboptimal glycemic control as evidenced by an HbA1c measurement at study start 7.1% and 11.0%, inclusive

• Have a body mass index (BMI) =45 kg/m^2

• Have been treated with lifestyle modification (diet and exercise) and with one of the following single oral antidiabetic agents (OADs) or combinations of OADs administered at maximum tolerated dose:

• metformin

• SU

• metformin plus an SU

• metformin plus pioglitazone

Exclusion Criteria:

• Have any contraindication, allergy, or hypersensitivity for the study drug (exenatide once weekly or liraglutide), exenatide twice daily, the OAD(s) being used, or the excipients contained in these agents

• If taking metformin and have a contraindication to metformin use

• Have been treated within 8 weeks of study start with systemic glucocorticoid therapy by oral, intravenous, intra-articular, or intramuscular route

• 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 study start

• Have taken any of the following excluded medications for more than 1 week within the 3 months prior to study start, or have taken any of the following excluded medications within 1 month prior to study start:

• Insulin

• Alpha-glucosidase inhibitors (e.g., Glyser® [miglitol] or Precose® [acarbose])

• Meglitinides (e.g., Prandin® [repaglinide] or Starlix® [nateglinide])

• Avandia® (rosiglitazone)

• Dipeptidyl peptidase (DPP)-4 inhibitors (e.g., Januvia™ [sitagliptin], Galvus® [vildagliptin], Onglyza™ [saxagliptin])

• Symlin® (pramlintide acetate)

• Have donated blood within 30 days prior to study start or have had a blood transfusion or severe blood loss within 3 months prior to study start

• Have at any time, including a clinical trial, taken exenatide once weekly, exenatide twice daily, liraglutide, or any other GLP-1 receptor agonist or GLP-1 analog

• Are currently enrolled in, or discontinued within the last 3 months or longer if required by local guidelines, from a clinical trial involving use of an investigational drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study

• Have previously been screen-failed from this study for any reason

• If a subject discontinues metformin, sulfonylurea, or pioglitazone prior to screening, the subject can be included if they discontinued the medication (whether alone or as component of combined medication) according to a specific schedule.

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, 2mg, once weekly
• liraglutide
subcutaneous injection, forced titration to 1.8mg, once daily

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research site	Mendoza
Argentina	Research Site	Rosario
Australia	Research Site	Box Hill
Australia	Research Site	Geelong
Australia	Research Site	Keswick
Austria	Research Site	Vienna
Belgium	Research site	Bonheiden
Belgium	Research Site	Edegem
Belgium	Research Site	Genk
Belgium	Research Site	Leuven
Belgium	Research Site	Liege
Canada	Research Site	Charlottetown
Canada	Research Site	Gatineau
Canada	Research Site	Ottawa
Canada	Research Site	Sherbrooke
Canada	Research Site	Vancouver
Canada	Research Site	Victoria
Canada	Research Site	Windsor
Canada	Research Site	Winnipeg
Czech Republic	Research Site	Brandys nad Labem
Czech Republic	Research Site	Prague 2
Czech Republic	Research Site	Prerov
France	Research Site	Grenoble
France	Research Site	Le Creuzot
France	Research Site	Marseille
France	Research Site	Marseille Cedex 5
France	Research Site	Marseille Cedex 9
France	Research Site	Paris
France	Research Site	Poitiers
France	Research Site	Reims Cedex
France	Research Site	Strasbourg
Germany	Research Site	Bad Staffelstein
Germany	Research Site	Beckum
Germany	Research Site	Biberach
Germany	Research Site	Datteln
Germany	Research Site	Dresden
Germany	Research Site	Essen
Germany	Research Site	Ludwigshafen
Germany	Research Site	Mainz
Germany	Research Site	Meissen
Germany	Research Site	Muenster
Germany	Research Site	Regensburg
Germany	Research Site	Riesa
Germany	Research Site	Stuttgart
Greece	Research Site	Athens
Greece	Research Site	Cholargos
Greece	Research Site	Patras
Hungary	Research Site	Bekescsaba
Hungary	Research Site	Budapest
Hungary	Research Site	Mako
Hungary	Research Site	Mosonmagyarovar
Hungary	Research Site	Nagykanizsa
Hungary	Research Site	Szekesfehervar
India	Research Site	Aligarh
India	Research Site	Bangalore
India	Research Site	Chennai
India	Research Site	Coimbatore
India	Research Site	Hyderabad
India	Research Site	Indore
India	Research Site	Karnal/Haryana
India	Research site	Karnataka
India	Research Site	Mumbai
India	Research Site	Pune
Israel	Research Site	Beer Sheva
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Raanana
Italy	Research Site	Bari
Italy	Research Site	Cagliari
Italy	Research Site	Catanzaro
Italy	Research Site	Chieti
Italy	Research Site	Napoli
Italy	Research Site	Roma
Italy	Research Site	Treviglio
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Ulsan
Mexico	Research Site	Guadalajara
Mexico	Research Site	Mexico
Mexico	Research Site	Monterrey
Poland	Research Site	Bialystok
Poland	Research Site	Krakow
Poland	Research Site	Lodz
Poland	Research Site	Poznan
Poland	Research site	Rzeszow
Poland	Research Site	Warszawa
Romania	Research site	Bucuresti
Romania	Research site	Galati
Romania	Research site	Iasi
Romania	Research site	Oradea
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Kosice
Slovakia	Research Site	Malacky
Slovakia	Research Site	Martin
South Africa	Research Site	Halfway House
South Africa	Research Site	Johannesburg
South Africa	Research Site	Kempton Park
South Africa	Research Site	Parktown
South Africa	Research Site	Pretoria
Spain	Research Site	Alcira
Spain	Research Site	Alicante
Spain	Research Site	Bilbao
Spain	Research Site	Madrid
Spain	Research Site	Majadahonda
Spain	Research Site	Teruel
Taiwan	Research Site	Changhua
Taiwan	Research Site	Jhonghe
Taiwan	Research Site	Sindian
Taiwan	Research Site	Taichung
Taiwan	Research Site	Yung-Kang, Tainan

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Eli Lilly and Company

Countries where clinical trial is conducted

Argentina,  Australia,  Austria,  Belgium,  Canada,  Czech Republic,  France,  Germany,  Greece,  Hungary,  India,  Israel,  Italy,  Korea, Republic of,  Mexico,  Poland,  Romania,  Slovakia,  South Africa,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c From Baseline to Week 26	Change in HbA1c from baseline to the treatment endpoint at 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 treatment endpoint at Week 26.	Baseline, Week 26	No
Secondary	Change in Fasting Serum Glucose From Baseline to Week 26	Change in fasting serum glucose from baseline to the treatment endpoint at Week 26.	Baseline, Week 26	No
Secondary	Change in Body Weight From Baseline to Week 26	Change in body weight from baseline to the treatment endpoint at Week 26.	Baseline, Week 26	No
Secondary	Change in Total Cholesterol From Baseline to Week 26	Change in total cholesterol from baseline to the treatment endpoint at Week 26.	Baseline, Week 26	No
Secondary	Change in High-Density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26	Change in HDL-C from baseline to the treatment endpoint at Week 26.	Baseline, Week 26	No
Secondary	Ratio of Fasting Triglycerides at Week 26 to Baseline	Ratio of fasting triglycerides (measured in mmol/L) treatment endpoint at Week 26 to baseline. Log(Postbaseline fasting triglycerides) - log(Baseline fasting triglycerides); change from baseline to the treatment endpoint at Week 26 is presented as ratio of Week 26 to baseline.	Baseline, Week 26	No
Secondary	Change in Systolic Blood Pressure (SBP) From Baseline to Week 26	Change in SBP from baseline to the treatment endpoint at Week 26.	Baseline, Week 26	No
Secondary	Change in Diastolic Blood Pressure (DBP) From Baseline to Week 26	Change in DBP from baseline to the treatment endpoint at Week 26.	Baseline, Week 26	No
Secondary	Assessment of Event Rate of Treatment-emergent Hypoglycemic Events	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 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. Event rate per subject year was calculated for each subject: (number of events observed from a subject/exposure from a subject)*365.25 where exposure = last post-baseline visit date - baseline visit date. Mean and Standard Error were then derived from ITT.	Baseline to Week 26	Yes