Type 2 Diabetes MellitusPhase 3NCT00434954

Effect of Exenatide Plus Metformin vs. Insulin Aspart Plus Metformin on Glycemic Control and Hypoglycemia in Patients With Type 2 Diabetes

A Phase 3 study testing exenatide twice daily (BID) and premixed insulin aspart twice daily (BID) in people with Type 2 Diabetes Mellitus, run by AstraZeneca at 39 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study in Germany is designed to compare the effects of twice-daily exenatide plus metformin and twice-daily premixed human insulin aspart plus metformin with respect to glycemic control, as measured by HbA1c, combined with the percentage of patients with at least one treatment-emergent hypoglycemic episode. Read more about this study

Who is it for?: Ages 18 to 90 years
Conditions the study is for: Type 2 Diabetes Mellitus
What is being tested?: exenatide twice daily (BID) and premixed insulin aspart twice daily (BID)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 494 participants
Where: 39 sitesGermany
Study dates: Feb 2007to Jun 2009
Phase: Phase 3
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 18 to 90 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Have been treated with diet and exercise and a stable, maximally tolerated dose of immediate-release or extended-release metformin, or the combination of metformin (any dosage) with sulfonylurea/meglitinides for at least 3 months prior to study start
Have not received thiazolidinediones, or alpha-glucosidase inhibitors for longer than 2 weeks within 3 months prior to study start, and have not received any insulin formulation for more than 14 days (other than in emergency situations) and within 14 days prior to study start
Have an HbA1c between 6.5% and 10.0%, inclusive
Have a body mass index (BMI) between 25 kg/m^2 and 40 kg/m^2, inclusive

Who cannot join

Have type 1 diabetes or known latent autoimmune diabetes in adults
Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 weeks prior to study start
Are receiving treatment for gastrointestinal disease with a drug directly affecting gastrointestinal motility (e.g., metoclopramide, cisapride, and chronic macrolide antibiotics)
Have used any prescription drug to promote weight loss within 3 months prior to study start
Have received treatment within 30 days prior to study start with a drug that has not received regulatory approval for any indication at the time of study entry
Have previously completed or withdrawn from this study or any other study investigating exenatide or GLP-1 analogs

Trial locations and contacts

39 sites in 1 country.

City, postcode or hospital

39 sites in 1 country

Germany39 sites

Research Site
Bad Mergentheim
Research Site
Berlin
Research Site
Bosenheim
Research Site
Burghausen
Research Site
Datteln
Research Site
Dresden
Research Site
Essen
Research Site
Friedrichsthal
Research Site
Hildesheim
Research Site
Hirschhorn
Research Site
Hohenmölsen
Research Site
Jena
Research Site
Lehrte
Research Site
Leipzig
Research Site
Ludwigsburg
Research Site
Mannheim
Research Site
Marburg
Research Site
Marktheidenfeld
Research Site
Meissen
Research Site
München
Research Site
Offenbach
Research Site
Oschatz
Research Site
Pohlheim
Research Site
Regensburg
Research Site
Riesa
Research Site
Rodgau
Research Site
Roding
Research Site
Rosenheim
Research Site
Schlüchtern
Research Site
Schwedt
Research Site
Sinsheim
Research Site
Speyer
Research Site
Unterhaching
Research Site
Völklingen
Research Site
Wallerfing
Research Site
Wangen
Research Site
Warburg
Research Site
Wiesbaden
Research Site
Wolfsburg

Other trials in Germany

About this study

Official title: Effect of Exenatide Plus Metformin vs. Premixed Human Insulin Aspart Plus Metformin on Glycemic Control and Hypoglycemia in Patients With Inadequate Control of Type 2 Diabetes on Oral Antidiabetic Treatment

Conditions: Type 2 Diabetes Mellitus
Being tested: exenatide twice daily (BID), premixed insulin aspart twice daily (BID)
Keywords: diabetes, exenatide, Byetta, Amylin, Lilly
Medical subject headings: Diabetes Mellitus, Type 2, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

exenatide twice daily (BID)Drug
Also called Byetta
subcutaneous injection (5 mcg or 10 mcg), twice a day
premixed insulin aspart twice daily (BID)Drug
subcutaneous injection (titrated appropriately), twice a day

Study groups in NCT00434954
Study group	Role	What they receive
Exenatide Twice Daily (BID)	Experimental	Not described Receives: Drug: exenatide twice daily (BID)
Premixed Insulin Aspart Twice Daily (BID)	Active comparator	Not described Receives: Drug: premixed insulin aspart twice daily (BID)

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Glycosylated Hemoglobin (HbA1c)
Change in HbA1c from baseline after 26 weeks of treatment (i.e., HbA1c at week 26 minus HbA1c at week 0)
Measured: Baseline and 26 weeks
Incidence of Hypoglycemia (Percentage of Participants With at Least One Hypoglycemic Episode)
Risk for first hypoglycemic episode (blood glucose <=3.9 mmol/L or severe episode) to occur up to week 26
Measured: 26 weeks

Secondary outcomes (10)

Percentage of Subjects Achieving HbA1c Target of < 6.5%
Percentage of subjects achieving HbA1c target of < 6.5% at the end of study (week 26) [i.e., number of subjects who achieved HbA1c < 6.5% divided by total number of subjects times 100%].
Measured: 26 weeks
Percentage of Subjects Achieving HbA1c Target of < 7.0%
Percentage of subjects achieving HbA1c target of < 7.0% at the end of study (week 26) [i.e., number of subjects who achieved HbA1c < 7.0% divided by total number of subjects times 100%].
Measured: 26 weeks
Incidence of Hypoglycemic Episodes [Blood Glucose <= 3.0 mmol/L or Severe] (Percentage of Subjects Who Experienced at Least One Treatment-emergent Hypoglycemic Episode During the 26-week Treatment Period)
Risk for the first hypoglycemic episode to occur up to Week 26 (percentage of subjects who experienced at least one treatment-emergent hypoglycemic episode during the 26-week treatment period)[ i.e., number of subjects experiencing at least one hypoglycemic episode divided by total number of subjects times 100%]
Measured: 26 weeks
Incidence of Nocturnal Hypoglycemia (Percentage of Subjects Who Experienced at Least One Episode of Nocturnal Hypoglycemia During the 26 Week Treatment Period)
Risk for first nocturnal (night-time) hypoglycemic episode to occur up to week 26 (percentage of subjects who experienced at least one episode of nocturnal hypoglycemia during the 26 week treatment period) [i.e., number of subjects who experienced nocturnal hypoglycemia divided by total number of subjects times 100%].
Measured: 26 weeks
7 Point Self-monitored Blood Glucose (SMBG) Profiles
7-point self-monitored blood glucose profiles at baseline and the end of the study, measured at 7 times during the day (pre-breakfast, 2 hours post-breakfast, pre-lunch, 2 hours post-lunch, pre-dinner, 2 hours post-dinner, and 3:00am).
Measured: Baseline and 26 weeks
Blood Lipid Levels
Total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol (calculated), and triglyceride levels at baseline (week 0) and the end of the study (week 26)
Measured: Baseline and 26 weeks
Change in Body Weight
Change in body weight from baseline after 26 weeks of treatment (i.e., body weight at week 26 minus body weight at week 0)
Measured: Baseline and 26 weeks
Change in Body Mass Index (BMI)
Change in BMI from baseline after 26 weeks of treatment (i.e., BMI at week 26 minus BMI at week 0)
Measured: Baseline and 26 weeks
Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ)
Total DTSQ treatment satisfaction score at baseline (week 0) and after 26 weeks of treatment (LOCF). Total DTSQ treatment satisfaction score is derived as sum score of the individual components 1 and 4-8 of the DTSQ questionnaire. Each component is scored on a scale of 0 (worst case) to 6 (best case). Higher values represent higher treatment satisfaction.
Measured: Baseline and 26 weeks
Patient Reported Outcomes: Quality of Life (SF-12)
SF-12 Physical and Mental Component Summary Scores at baseline (week 0) and after 26 weeks of treatment (LOCF). SF-12 Physical and Mental Component Summary Scores are normalized scores ranging from 0 (worst case) to 100 (best case), and are derived from responses to 12 questions. Scores > 50 indicate an above-average health status.
Measured: Baseline and 26 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2007Jun 2009

First posted14 Feb 2007 (estimated)
Study startFeb 2007
Primary completionJun 2009
Study completionJun 2009

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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 494 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00434954
Sponsor's protocol ID: H8O-SB-GWBN
Status last verified: Mar 2015
First submitted: 12 Feb 2007
Last updated: 7 Apr 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Pencek R, Blickensderfer A, Li Y, Brunell SC, Anderson PW. Exenatide twice daily: analysis of effectiveness and safety data stratified by age, sex, race, duration of diabetes, and body mass index. Postgrad Med. 2012 Jul;124(4):21-32. doi: 10.3810/pgm.2012.07.2567.
PubMed 22913891
Gallwitz B, Bohmer M, Segiet T, Molle A, Milek K, Becker B, Helsberg K, Petto H, Peters N, Bachmann O. Exenatide twice daily versus premixed insulin aspart 70/30 in metformin-treated patients with type 2 diabetes: a randomized 26-week study on glycemic control and hypoglycemia. Diabetes Care. 2011 Mar;34(3):604-6. doi: 10.2337/dc10-1900. Epub 2011 Feb 1.
PubMed 21285388

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Type 2 Diabetes Mellitus trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effect of Exenatide Plus Metformin vs. Premixed Human Insulin Aspart Plus Metformin on Glycemic Control and Hypoglycemia in Patients With Inadequate Control of Type 2 Diabetes on Oral Antidiabetic Treatment
ClinicalTrials.gov ID: NCT00434954
Acronym / sponsor ID: H8O-SB-GWBN
Conditions: Type 2 Diabetes Mellitus
Keywords: diabetes, exenatide, Byetta, Amylin, Lilly
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 494 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Eli Lilly and Company
Study start: Feb 2007
Primary completion: Jun 2009 (actual)
Study completion: Jun 2009 (actual)
First posted: 14 Feb 2007 (estimated)
Results: Posted 23 Aug 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Exenatide Twice Daily (BID)	Experimental	Drug: exenatide twice daily (BID)
Premixed Insulin Aspart Twice Daily (BID)	Active comparator	Drug: premixed insulin aspart twice daily (BID)

Who may qualify

Ages: 18 to 90 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Have been treated with diet and exercise and a stable, maximally tolerated dose of immediate-release or extended-release metformin, or the combination of metformin (any dosage) with sulfonylurea/meglitinides for at least 3 months prior to study start
Have not received thiazolidinediones, or alpha-glucosidase inhibitors for longer than 2 weeks within 3 months prior to study start, and have not received any insulin formulation for more than 14 days (other than in emergency situations) and within 14 days prior to study start
Have an HbA1c between 6.5% and 10.0%, inclusive
Have a body mass index (BMI) between 25 kg/m^2 and 40 kg/m^2, inclusive

Key exclusion criteria (6 listed)

Have type 1 diabetes or known latent autoimmune diabetes in adults
Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 weeks prior to study start
Are receiving treatment for gastrointestinal disease with a drug directly affecting gastrointestinal motility (e.g., metoclopramide, cisapride, and chronic macrolide antibiotics)
Have used any prescription drug to promote weight loss within 3 months prior to study start
Have received treatment within 30 days prior to study start with a drug that has not received regulatory approval for any indication at the time of study entry

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
exenatide twice daily (BID)Also: Byettasubcutaneous injection (5 mcg or 10 mcg), twice a day	Drug	Exenatide Twice Daily (BID)
premixed insulin aspart twice daily (BID)subcutaneous injection (titrated appropriately), twice a day	Drug	Premixed Insulin Aspart Twice Daily (BID)

Primary outcome

Change in Glycosylated Hemoglobin (HbA1c)
Time frame: Baseline and 26 weeks
Change in HbA1c from baseline after 26 weeks of treatment (i.e., HbA1c at week 26 minus HbA1c at week 0)
Incidence of Hypoglycemia (Percentage of Participants With at Least One Hypoglycemic Episode)
Time frame: 26 weeks
Risk for first hypoglycemic episode (blood glucose <=3.9 mmol/L or severe episode) to occur up to week 26

10 secondary outcomes

Percentage of Subjects Achieving HbA1c Target of < 6.5%
Time frame: 26 weeks
Percentage of Subjects Achieving HbA1c Target of < 7.0%
Time frame: 26 weeks
Incidence of Hypoglycemic Episodes [Blood Glucose <= 3.0 mmol/L or Severe] (Percentage of Subjects Who Experienced at Least One Treatment-emergent Hypoglycemic Episode During the 26-week Treatment Period)
Time frame: 26 weeks
Incidence of Nocturnal Hypoglycemia (Percentage of Subjects Who Experienced at Least One Episode of Nocturnal Hypoglycemia During the 26 Week Treatment Period)
Time frame: 26 weeks
7 Point Self-monitored Blood Glucose (SMBG) Profiles
Time frame: Baseline and 26 weeks
Blood Lipid Levels
Time frame: Baseline and 26 weeks
Change in Body Weight
Time frame: Baseline and 26 weeks
Change in Body Mass Index (BMI)
Time frame: Baseline and 26 weeks
Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ)
Time frame: Baseline and 26 weeks
Patient Reported Outcomes: Quality of Life (SF-12)
Time frame: Baseline and 26 weeks

Results and safety

Results posted to the registry on 23 Aug 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Exenatide Twice Daily	248	166
Premixed Insulin Aspart Twice Daily	246	175

Primary outcome: Change in Glycosylated Hemoglobin (HbA1c)

Time frame: Baseline and 26 weeks. Least squares mean (Standard Error). Unit: Percentage of glycosylated hemoglobin

Measure	Exenatide Twice Daily n = 181	Premixed Insulin Aspart Twice Daily n = 173
Value	-1.00 (0.05)	-1.14 (0.05)

Exenatide Twice Daily vs Premixed Insulin Aspart Twice Daily: Mean Difference (Net): 0.14 (95% CI -0.003 to 0.291), p = 0.055, Mixed effect model repeat measures(MMRM)

Population analysed: All randomized patients who were previously treated with metformin only and who received at least one dose of study drug (MET only, FAS) and had baseline and at least one post-baseline value available

Primary outcome: Incidence of Hypoglycemia (Percentage of Participants With at Least One Hypoglycemic Episode)

Time frame: 26 weeks. Number. Unit: Percentage of participants

Measure	Exenatide Twice Daily n = 181	Premixed Insulin Aspart Twice Daily n = 173
Value	8.0	20.5

Exenatide Twice Daily vs Premixed Insulin Aspart Twice Daily: p <0.05, Kaplan-Meier analysis

Population analysed: All randomized patients who were previously treated with metformin only and who received at least one dose of study drug (MET only, FAS)

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: 26 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Exenatide Twice Daily	9 of 247 (3.6%)	102 of 247 (41.3%)	Not reported
Premixed Insulin Aspart Twice Daily	8 of 233 (3.4%)	66 of 233 (28.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 22913891Pencek R, Blickensderfer A, Li Y, Brunell SC, Anderson PW. Exenatide twice daily: analysis of effectiveness and safety data stratified by age, sex, race, duration of diabetes, and body mass index. Postgrad Med. 2012 Jul;124(4):21-32. doi: 10.3810/pgm.2012.07.2567.
Derived from this study: PubMed 21285388Gallwitz B, Bohmer M, Segiet T, Molle A, Milek K, Becker B, Helsberg K, Petto H, Peters N, Bachmann O. Exenatide twice daily versus premixed insulin aspart 70/30 in metformin-treated patients with type 2 diabetes: a randomized 26-week study on glycemic control and hypoglycemia. Diabetes Care. 2011 Mar;34(3):604-6. doi: 10.2337/dc10-1900. Epub 2011 Feb 1.

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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.

Chief Medical Officer, MD study director

Eli Lilly and Company

39 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing exenatide twice daily (BID) and premixed insulin aspart twice daily (BID) in people with Type 2 Diabetes Mellitus, run by AstraZeneca at 39 sites in Germany.

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 4 inclusion and 6 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 7 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 39 sites in Germany. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 23 Aug 2010). 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?

Change in Glycosylated Hemoglobin (HbA1c) (time frame: Baseline and 26 weeks). The study lists 2 primary outcomes in all. 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 NCT00434954, 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 7 Apr 2015.