Saxagliptin Compared to Glimepiride in Elderly Type 2 Diabetes Patients, With Inadequate Glycemic Control on Metformin

Type 2 Diabetes Mellitus Clinical Trial

— GENERATION  

Official title:

A 52-Week, Randomised, Double Blind, Active-Controlled, Multi-Centre Phase IIIb/IV Study to Evaluate the Efficacy and Tolerability of Saxagliptin Compared to Glimepiride in Elderly Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycaemic Control on Metformin Monotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01006603
• Other study ID #: D1680L00002
• Status: Completed
• Phase: Phase 4
• First received: October 31, 2009
• Last updated: September 27, 2013
• Start date: October 2009
• Est. completion date: June 2012

Study information

• Verified date: September 2013
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food SafetyDenmark: Danish Dataprotection AgencyDenmark: Danish Medicines AgencyDenmark: Ethics CommitteeFinland: Ethics CommitteeFinland: Finnish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: Institutional Ethical CommitteeGermany: Ethics CommissionGermany: Federal Institute for Drugs and Medical DevicesGreece: Ethics CommitteeGreece: Ministry of Health and WelfareGreece: National Organization of MedicinesItaly: Ethics CommitteeItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthNorway: Data Protection AuthorityNorway: Norwegian Medicines AgencyNorway:National Committee for Medical and Health Research EthicsSpain: Comité Ético de Investigación ClínicaSpain: Spanish Agency of MedicinesSweden: Medical Products AgencySweden: Regional Ethical Review BoardUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: National Health ServiceUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy and tolerability of saxagliptin compared to glimepiride in elderly patients with type 2 diabetes mellitus who have inadequate glycaemic control on metformin monotherapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 957
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• Provision of informed consent prior to any study specific procedures

• Established clinical diagnosis of type 2 diabetes. Treatment with a stable metformin monotherapy, for at least 8 weeks prior to Visit 1

• HbA1c =7.0% and =9.0%

Exclusion Criteria:

• Type 1 diabetes, history of diabetic ketoacidosis or hyperosmolar non-ketonic coma. Current use of any injectable or oral antihyperglycemic agent excluding metformin.

• Renal impairment as defined by a creatinine clearance <60 mL/min

• Individuals who, in the opinion of the investigator, in which participation in this study may pose a significant risk to the patient and could render the patient unable to successfully complete the 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
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Saxagliptin
5 mg, oral tablet, once daily
• Glimepiride
1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily

Locations

Country	Name	City	State
Austria	Research Site	Feldbach
Austria	Research Site	Graz
Austria	Research Site	Salzburg
Austria	Research Site	Vienna
Austria	Research Site	Wien
Denmark	Research Site	Aalborg
Denmark	Research Site	Ans by
Denmark	Research Site	Kjellerup
Denmark	Research Site	Kolding
Denmark	Research Site	Norresundby
Denmark	Research Site	Roskilde
Denmark	Research Site	Roslev
Denmark	Research Site	Vaerlose
Denmark	Research Site	Viborg
Denmark	Research Site	Viby J
Finland	Research Site	Harjavalta
Finland	Research Site	Helsinki
Finland	Research Site	Kuopio
Finland	Research Site	Kuusankoski
Finland	Research Site	Lahti
Finland	Research Site	Oulu
Finland	Research Site	Seinajoki
Finland	Research Site	Sipoo
Finland	Research Site	Tampere
Finland	Research Site	Turku
Finland	Research Site	Vantaa
Finland	Research Site	Vimpeli
France	Research Site	Chatellerault
France	Research Site	La Rochelle
France	Research Site	La Seyne Sur Mer
France	Research Site	Laval
France	Research Site	Seysses
France	Research Site	Strasbourg
France	Research Site	Tierce
Germany	Research Site	Augsburg
Germany	Research Site	Darmstadt
Germany	Research Site	Dresden
Germany	Research Site	Essen
Germany	Research Site	Gelnhausen
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg	HH
Germany	Research Site	Magdeburg
Germany	Research Site	Mayen
Germany	Research Site	Munchen
Germany	Research Site	Neumunster
Germany	Research Site	Nurnberg
Germany	Research Site	Pirna
Germany	Research Site	Ratzeburg
Germany	Research Site	Reinfeld
Germany	Research Site	Sulzbach
Greece	Research Site	Athens
Greece	Research Site	Nikea
Greece	Research Site	Thessaloniki
Hungary	Research Site	ACS
Hungary	Research Site	Balatonfured
Hungary	Research Site	Budapest
Hungary	Research Site	ERD
Hungary	Research Site	Gyongyos
Hungary	Research Site	Komarom
Italy	Research Site	Chieti
Italy	Research Site	Milano	MI
Italy	Research Site	Napoli
Italy	Research Site	Padova	PD
Italy	Research Site	Palermo	PA
Italy	Research Site	Pordenone	PN
Italy	Research Site	Reggio Emilia	RE
Italy	Research Site	Roma
Italy	Research Site	Viterbo
Mexico	Research Site	Durango
Mexico	Research Site	Guadalajara	Jalisco
Mexico	Research Site	Monterrey	Nuevo Leon
Norway	Research Site	Aksdal
Norway	Research Site	Alesund
Norway	Research Site	Elverum
Norway	Research Site	Halden
Norway	Research Site	Hamar
Norway	Research Site	Kirkenaer
Norway	Research Site	Kongsvinger
Norway	Research Site	Larvik
Norway	Research Site	Lierskogen
Norway	Research Site	Nord-lenangen
Norway	Research Site	Oslo
Norway	Research Site	ROA
Norway	Research Site	Sandvika
Norway	Research Site	Skedsmokorset
Norway	Research Site	Sorumsand
Norway	Research Site	Svelvik
Norway	Research Site	Trondheim
Norway	Research Site	Ulset
Spain	Research Site	A Coruna	Galicia
Spain	Research Site	Alicante	Comunidad Valenciana
Spain	Research Site	Begonte (lugo)	Galicia
Spain	Research Site	Getafe	Comunidad de Madrid
Spain	Research Site	Madrid	Comunidad de Madrid
Spain	Research Site	Oviedo	Asturias
Spain	Research Site	San Sebastian de Los Reyes	Comunidad de Madrid
Spain	Research Site	Sevilla	Andalucia
Spain	Research Site	Zamora	Castilla Y Leon
Sweden	Research Site	Finspang
Sweden	Research Site	Gavle
Sweden	Research Site	Goteborg
Sweden	Research Site	Jarfalla
Sweden	Research Site	Jonkoping
Sweden	Research Site	Lessebo
Sweden	Research Site	Lund
Sweden	Research Site	Odeshog
Sweden	Research Site	Pitea
Sweden	Research Site	Rattvik
Sweden	Research Site	Stockholm
Sweden	Research Site	Trollhattan
Sweden	Research Site	Vastervik
United Kingdom	Research Site	Annan	Dumfries and Galloway
United Kingdom	Research Site	Ayrshire
United Kingdom	Research Site	Barnstaple	Devon
United Kingdom	Research Site	Bath
United Kingdom	Research Site	Bradford-on-avon	Wiltshire
United Kingdom	Research Site	Canterbury	Kent
United Kingdom	Research Site	Cumbernauld
United Kingdom	Research Site	Dundee
United Kingdom	Research Site	Fowey	Cornwall
United Kingdom	Research Site	Frome	Somerset
United Kingdom	Research Site	Hamilton
United Kingdom	Research Site	Middlesex
United Kingdom	Research Site	Motherwell
United Kingdom	Research Site	Nr Penzance	Cornwall
United Kingdom	Research Site	Penzance	Cornwall
United Kingdom	Research Site	Plymouth	Devon
United Kingdom	Research Site	Somerset
United Kingdom	Research Site	Trowbridge	Wiltshire
United Kingdom	Research Site	Wellingborough
United Kingdom	Research Site	Whitstable	Kent

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Bristol-Myers Squibb

Countries where clinical trial is conducted

Austria,  Denmark,  Finland,  France,  Germany,  Greece,  Hungary,  Italy,  Mexico,  Norway,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients Reaching HbA1c <7% After 52 Weeks of Treatment Without Confirmed or Severe Hypoglycaemia.	Defined as obtained on or before the 8th day after the last dosing day, as determined by central laboratory. Safety analysis set.; Confirmed hypoglycaemia defined as: any event defined as either a symptomatic event with blood glucose level <3 mmol/L (<54 mg/dL) and no need for external assistance, or an asymptomatic blood glucose measurement <3 mmol/L (<54 mg/dL).; Major (or severe) hypoglycaemia defined as: symptomatic events requiring external assistance due to severe impairment in consciousness or behaviour, with or without blood glucose level <3 mmol/L (<54 mg/dL), but with prompt recovery after glucose or glucagon administration. These events may be associated with sufficient neuroglycopenia to induce seizure or coma. Plasma glucose measurements may not be available during such an event, but neurological recovery, attributable to the restoration of plasma glucose to normal, was considered sufficient evidence that the event was induced by a low plasma glucose concentration.	From week 0 to week 52.	Yes
Secondary	Proportion of Patients Having Experienced at Least One Hypoglycaemic Event (Confirmed or Severe) Over the 52-week Double-blind Treatment Period.	Hypoglyceamic event defined as, Confirmed hypoglycaemia: any event defined as either a symptomatic event with blood glucose level <3 mmol/L (<54 mg/dL) and no need for external assistance, or an asymptomatic blood glucose measurement <3 mmol/L (<54 mg/dL).; Major (or severe) hypoglycaemia: symptomatic events requiring external assistance due to severe impairment in consciousness or behaviour, with or without blood glucose level <3 mmol/L (<54 mg/dL), but with prompt recovery after glucose or glucagon administration. These events may be associated with sufficient neuroglycopenia to induce seizure or coma. Plasma glucose measurements may not be available during such an event, but neurological recovery, attributable to the restoration of plasma glucose to normal, was considered sufficient evidence that the event was induced by a low plasma glucose concentration. Safety analysis set.	From week 0 to week 52.	Yes
Secondary	Change From Baseline to Week 52 in HbA1c.	Measured as the difference between the last on-treatment value (defined as obtained before or on the 8th day after the last dosing date), and the last pre-randomisation HbA1c value, as determined by central laboratory. Full analysis set.	From week 0 to week 52.	No
Secondary	Proportion of Patients Achieving a Therapeutic Glycaemic Response at Week 52 Defined as HbA1c <7.0%	Proportion of patients with their last on-treatment value (defined as obtained before or on the 8th day after the last dosing date), as determined by central laboratory, below the specified limits. Full analysis set.	From week 0 to week 52	No
Secondary	Change From Baseline to Week 52 in Fasting Plasma Glucose (FPG)	Measured as the difference between the last on-treatment value (defined as obtained before or on the first day after the last dosing date)and the last pre-randomisation fasting plasma glucose value, as determined by central laboratory. Full analysis set.	From week 0 to week 52	No
Secondary	Change From Baseline to Week 52 in Insulin	Measured as the difference between the last on-treatment value (defined as obtained before or on the first day after the last dosing date) and the last pre-randomisation fasting plasma insulin value, as determined by central laboratory. Full analysis set.	From week 0 to week 52	No
Secondary	Change From Baseline to Week 52 in ß-cell Function (as Measured by Homeostasis Model Assessment-ß [HOMA-ß]	ß-cell function as estimated by the homeostasis model assessment (HOMA) model. Value is derived from FPG and fasting insulin; fasting insulin values below 2.074 µU/mL or above 57.595 µU/mL and FPG values below 3 mmol/L or above 25 mmol/L are excluded (as restricted by the calculation method used). Full analysis set.	From week 0 to week 52	No