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

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01006603
First received: October 31, 2009
Last updated: September 27, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Saxagliptin
Drug: Glimepiride
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Proportion of Patients Reaching HbA1c <7% After 52 Weeks of Treatment Without Confirmed or Severe Hypoglycaemia. [ Time Frame: From week 0 to week 52. ] [ Designated as safety issue: Yes ]

    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.



Secondary Outcome Measures:
  • Proportion of Patients Having Experienced at Least One Hypoglycaemic Event (Confirmed or Severe) Over the 52-week Double-blind Treatment Period. [ Time Frame: From week 0 to week 52. ] [ Designated as safety issue: Yes ]

    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.


  • Change From Baseline to Week 52 in HbA1c. [ Time Frame: From week 0 to week 52. ] [ Designated as safety issue: No ]
    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.

  • Proportion of Patients Achieving a Therapeutic Glycaemic Response at Week 52 Defined as HbA1c <7.0% [ Time Frame: From week 0 to week 52 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to Week 52 in Fasting Plasma Glucose (FPG) [ Time Frame: From week 0 to week 52 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to Week 52 in Insulin [ Time Frame: From week 0 to week 52 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to Week 52 in β-cell Function (as Measured by Homeostasis Model Assessment-β [HOMA-β] [ Time Frame: From week 0 to week 52 ] [ Designated as safety issue: No ]
    β-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.


Enrollment: 957
Study Start Date: October 2009
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Saxagliptin 5 mg
Drug: Saxagliptin
5 mg, oral tablet, once daily
Other Name: Onglyza
Active Comparator: 2
Glimepiride 1 - 6 mg
Drug: Glimepiride
1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily
Other Name: Amaryl

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01006603

  Show 131 Study Locations
Sponsors and Collaborators
AstraZeneca
Bristol-Myers Squibb
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01006603     History of Changes
Other Study ID Numbers: D1680L00002
Study First Received: October 31, 2009
Results First Received: June 12, 2013
Last Updated: September 27, 2013
Health Authority: Austria: Agency for Health and Food Safety
Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency
Denmark: Ethics Committee
Finland: Ethics Committee
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Institutional Ethical Committee
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Greece: Ethics Committee
Greece: Ministry of Health and Welfare
Greece: National Organization of Medicines
Italy: Ethics Committee
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Norway: Data Protection Authority
Norway: Norwegian Medicines Agency
Norway:National Committee for Medical and Health Research Ethics
Spain: Comité Ético de Investigación Clínica
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Sweden: Regional Ethical Review Board
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
United Kingdom: Research Ethics Committee

Keywords provided by AstraZeneca:
Type 2 Diabetes Mellitus
elderly patients
saxagliptin
randomised
double-blind

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Glimepiride
Saxagliptin
Anti-Arrhythmia Agents
Cardiovascular Agents
Dipeptidyl-Peptidase IV Inhibitors
Enzyme Inhibitors
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Immunologic Factors
Immunosuppressive Agents
Incretins
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014