Type 2 Diabetes MellitusPhase 4GENERATIONNCT01006603
Saxagliptin Compared to Glimepiride in Elderly Type 2 Diabetes Patients, With Inadequate Glycemic Control on Metformin
A Phase 4 study testing Saxagliptin and Glimepiride in people with Type 2 Diabetes Mellitus, run by AstraZeneca at 131 sites in 13 countries.
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. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- Saxagliptin and Glimepiride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 957 participants
- Where
- 131 sitesin 13 countries
- Study dates
- Oct 2009to Jun 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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%
Who cannot join
- 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
Trial locations and contacts
131 sites in 13 countries.
131 sites in 13 countries
United Kingdom20 sites
Research Site
Annan, Dumfries and Galloway
Research Site
Ayrshire
Research Site
Barnstaple, Devon
Research Site
Bath
Research Site
Bradford on Avon, Wiltshire
Research Site
Canterbury, Kent
Research Site
Cumbernauld
Research Site
Dundee
Research Site
Fowey, Cornwall
Research Site
Frome, Somerset
Research Site
Hamilton
Research Site
Middlesex
Research Site
Motherwell
Research Site
Nr Penzance, Cornwall
Research Site
Penzance, Cornwall
Research Site
Plymouth, Devon
Research Site
Somerset
Research Site
Trowbridge, Wiltshire
Research Site
Wellingborough
Research Site
Whitstable, Kent
Norway18 sites
Research Site
Aksdal
Research Site
Ålesund
Research Site
Elverum
Research Site
Halden
Research Site
Hamar
Research Site
Kirkenær
Research Site
Kongsvinger
Research Site
Larvik
Research Site
Lierskogen
Research Site
Nordlenangen
Research Site
Oslo
Research Site
Røa
Research Site
Sandvika
Research Site
Skedsmokorset
Research Site
Sørumsand
Research Site
Svelvik
Research Site
Trondheim
Research Site
Ulset
Germany16 sites
Research Site
Augsburg
Research Site
Darmstadt
Research Site
Dresden
Research Site
Essen
Research Site
Gelnhausen
Research Site
Hamburg, Free and Hanseatic City of Hamburg
Research Site
Hamburg
Research Site
Magdeburg
Research Site
Mayen
Research Site
München
Research Site
Neumünster
Research Site
Nuremberg
Research Site
Pirna
Research Site
Ratzeburg
Research Site
Reinfeld
Research Site
Sulzbach
Sweden13 sites
Research Site
Finspång
Research Site
Gävle
Research Site
Gothenburg
Research Site
Jarfalla
Research Site
Jönköping, Sweden
Research Site
Lessebo
Research Site
Lund
Research Site
Ödeshög
Research Site
Piteå
Research Site
Rättvik
Research Site
Stockholm
Research Site
Trollhättan
Research Site
Västervik
Finland12 sites
Research Site
Harjavalta
Research Site
Helsinki
Research Site
Kuopio
Research Site
Kuusankoski
Research Site
Lahti, Finland
Research Site
Oulu
Research Site
Seinäjoki
Research Site
Sipoo
Research Site
Tampere
Research Site
Turku
Research Site
Vantaa, Finland
Research Site
Vimpeli
Denmark10 sites
Research Site
Aalborg
Research Site
Ans
Research Site
Kjellerup
Research Site
Kolding
Research Site
Nørresundby
Research Site
Roskilde
Research Site
Roslev
Research Site
Værløse
Research Site
Viborg
Research Site
Viby J
Italy9 sites
Research Site
Chieti
Research Site
Milan, MI
Research Site
Naples
Research Site
Padova, PD
Research Site
Palermo, PA
Research Site
Pordenone, PN
Research Site
Reggio Emilia, RE
Research Site
Roma
Research Site
Viterbo
Spain9 sites
Research Site
A Coruña, Galicia
Research Site
Alicante, Valencia
Research Site
Begonte (lugo), Galicia
Research Site
Getafe, Madrid
Research Site
Madrid, Madrid
Research Site
Oviedo, Principality of Asturias
Research Site
San Sebastián de los Reyes, Madrid
Research Site
Seville, Andalusia
Research Site
Zamora, Castille and León
France7 sites
Research Site
Châtellerault
Research Site
La Rochelle
Research Site
La Seyne-sur-Mer
Research Site
Laval
Research Site
Seysses
Research Site
Strasbourg
Research Site
Tiercé
Hungary6 sites
Research Site
Ács
Research Site
Balatonfüred
Research Site
Budapest
Research Site
Érd
Research Site
Gyöngyös
Research Site
Komárom
Austria4 sites
Research Site
Feldbach
Research Site
Graz
Research Site
Salzburg
Research Site
Vienna
Greece4 sites
Research Site
Athens, Greece
Research Site
Athens
Research Site
Nikaia
Research Site
Thessaloniki
Mexico3 sites
Research Site
Durango, Durango
Research Site
Guadalajara, Jalisco
Research Site
Monterrey, Nuevo León
About this study
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
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.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- Saxagliptin, Glimepiride
- Keywords
- Type 2 Diabetes Mellitus, elderly patients, saxagliptin, randomised, double-blind
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SaxagliptinDrug
Also called Onglyza
5 mg, oral tablet, once daily
GlimepirideDrug
Also called Amaryl
1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Saxagliptin 5 mg Receives: Drug: Saxagliptin |
| 2 | Active comparator | Glimepiride 1 - 6 mg Receives: Drug: Glimepiride |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From week 0 to week 52.
Secondary outcomes (6)
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.
Measured: From week 0 to week 52.
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.
Measured: From week 0 to week 52.
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.
Measured: From week 0 to week 52
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.
Measured: From week 0 to week 52
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.
Measured: From week 0 to week 52
Change From Baseline to Week 52 in β-cell Function (as Measured by Homeostasis Model Assessment-β [HOMA-β]
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.
Measured: From week 0 to week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2009 (estimated)
- Study startOct 2009
- Primary completionJun 2012
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 957 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01006603
- Sponsor's protocol ID
- D1680L00002
- Acronym
- GENERATION
- Status last verified
- Sep 2013
- First submitted
- 31 Oct 2009
- Last updated
- 28 Nov 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Perl S, Cook W, Wei C, Ohman P, Hirshberg B. Effects of Glimepiride versus Saxagliptin on beta-Cell Function and Hypoglycemia: A Post Hoc Analysis in Older Patients with Type 2 Diabetes Inadequately Controlled with Metformin. Clin Ther. 2016 Dec;38(12):2578-2588. doi: 10.1016/j.clinthera.2016.10.006. Epub 2016 Nov 4.
PubMed 27823868Schernthaner G, Duran-Garcia S, Hanefeld M, Langslet G, Niskanen L, Ostgren CJ, Malvolti E, Hardy E. Efficacy and tolerability of saxagliptin compared with glimepiride in elderly patients with type 2 diabetes: a randomized, controlled study (GENERATION). Diabetes Obes Metab. 2015 Jul;17(7):630-8. doi: 10.1111/dom.12461. Epub 2015 Apr 7.
PubMed 25761977
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01006603
- Acronym / sponsor ID
- GENERATION / D1680L00002
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- Type 2 Diabetes Mellitus, elderly patients, saxagliptin, randomised, double-blind
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 957 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Study start
- Oct 2009
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 3 Nov 2009 (estimated)
- Results
- Posted 28 Nov 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: SaxagliptinSaxagliptin 5 mg |
| 2 | Active comparator | Drug: GlimepirideGlimepiride 1 - 6 mg |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (3 listed)
- 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%
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SaxagliptinAlso: Onglyza5 mg, oral tablet, once daily | Drug | 1 |
| GlimepirideAlso: Amaryl1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily | Drug | 2 |
Primary outcome
Proportion of Patients Reaching HbA1c <7% After 52 Weeks of Treatment Without Confirmed or Severe Hypoglycaemia.
Time frame: From week 0 to week 52.
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.
6 secondary outcomes
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.
Change From Baseline to Week 52 in HbA1c.
Time frame: From week 0 to week 52.
Proportion of Patients Achieving a Therapeutic Glycaemic Response at Week 52 Defined as HbA1c <7.0%
Time frame: From week 0 to week 52
Change From Baseline to Week 52 in Fasting Plasma Glucose (FPG)
Time frame: From week 0 to week 52
Change From Baseline to Week 52 in Insulin
Time frame: From week 0 to week 52
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27823868Perl S, Cook W, Wei C, Ohman P, Hirshberg B. Effects of Glimepiride versus Saxagliptin on beta-Cell Function and Hypoglycemia: A Post Hoc Analysis in Older Patients with Type 2 Diabetes Inadequately Controlled with Metformin. Clin Ther. 2016 Dec;38(12):2578-2588. doi: 10.1016/j.clinthera.2016.10.006. Epub 2016 Nov 4.
- Derived from this study: PubMed 25761977Schernthaner G, Duran-Garcia S, Hanefeld M, Langslet G, Niskanen L, Ostgren CJ, Malvolti E, Hardy E. Efficacy and tolerability of saxagliptin compared with glimepiride in elderly patients with type 2 diabetes: a randomized, controlled study (GENERATION). Diabetes Obes Metab. 2015 Jul;17(7):630-8. doi: 10.1111/dom.12461. Epub 2015 Apr 7.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
131 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Saxagliptin and Glimepiride in people with Type 2 Diabetes Mellitus, run by AstraZeneca at 131 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 131 sites in United Kingdom, Norway, Germany, Sweden, Finland and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Patients Reaching HbA1c <7% After 52 Weeks of Treatment Without Confirmed or Severe Hypoglycaemia. (time frame: From week 0 to week 52.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01006603, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2013.