Safety of Exenatide Once Weekly in Patients With Type 2 Diabetes Mellitus Treated With Thiazolidinedione Alone or Thiazolidinedione in Combination With Metformin

A Phase 3 study testing exenatide in people with Type 2 Diabetes, run by AstraZeneca at 26 sites in 5 countries.

Completed

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

Trial summary

This study will examine the safety of exenatide once weekly (2.0 mg) in approximately 134 patients receiving treatment with thiazolidinedione alone or thiazolidinedione in combination with metformin. Patients are expected to be treated with exenatide once weekly for at least 52 weeks. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Type 2 Diabetes
What is being tested?: exenatide
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 134 participants
Where: 26 sitesin 5 countries
Study dates: Oct 2008to Nov 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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Have type 2 diabetes
At least 18 years of age at screening.
Have HbA1c of 7.1% to 10.0%, inclusive, at screening.
Have a body mass index (BMI) of 25 kg/m2 to 45 kg/m2, inclusive.
Have been treated with a stable dose of TZD (≥4 mg/day rosiglitazone or ≥30 mg/day pioglitazone) for at least 120 days prior to Visit 1 OR Have been treated with a stable dose of TZD (≥4 mg/day rosiglitazone or ≥30 mg/day pioglitazone) for at least 120 days PLUS a stable dose of metformin for at least 90 days prior to Visit 1.
Have a history of stable body weight (not varying by >10% for at least 3 months prior to screening).

Show all 12Show fewer

If female of child-bearing potential (not surgically sterilized and between menarche and 1-year postmenopause) only.
Are not breastfeeding.
Test negative for pregnancy at the time of screening based on a serum pregnancy test.
Intend not to become pregnant during the study.
Have practiced a reliable method of birth control (e.g., use of oral contraceptives or approved hormonal implant; diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices; partner with vasectomy; or abstinence) for at least 6 weeks prior to screening.
Agree to continue to use a reliable method of birth control (see above) during the study.

Who cannot join

Have had a clinically significant history of cardiac disease or presence of active cardiac disease within the year prior to inclusion in the study, including myocardial infarction, clinically significant arrhythmia, unstable angina, coronary artery bypass surgery, angioplasty.
Is expected to require coronary artery bypass surgery or angioplasty during the course of the study.
Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis
Have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine ≥135 μmol/L for males and ≥110 μmol/L for females.
Have active or untreated malignancy, or have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years.
Have known hemoglobinopathy or chronic anemia (hemoglobin concentration <11.5 g/dL [115 g/L] for males, <10.5 g/dL [105 g/L] for females).

Show all 20Show fewer

Have clinically significant history or presence of severe gastrointestinal disease, particularly those which may impact gastric emptying, such as gastroparesis, pyloric stenosis, or gastric bypass surgery.
Have a history of pancreatitis.
Have had greater than three episodes of major hypoglycemia within 6 months prior to screening.
Have any contraindication for the OAD(s) which they use, according to local label requirements.
Are known to have active proliferative retinopathy.
Are receiving chronic (>2 weeks) systemic glucocorticoid therapy (excluding topical or inhaled preparations) or have received systemic glucocorticoid therapy for >2 weeks within the 4 weeks immediately preceding screening.
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 screening.
Have previously been treated with glucagon-like peptide 1 analogs or liraglutide.
Have been treated for longer than 2 weeks with any of the following excluded medications within 3 months prior to screening: Insulin; Sulfonylureas; Alpha-glucosidase inhibitors (e.g., Glyset® [miglitol] or Precose® [acarbose]); Meglitinides (e.g., Prandin® [repaglinide] or Starlix® [nateglinide]); Dipeptidyl peptidase (DPP)-4 inhibitors (e.g., Januvia™ [sitagliptin], Galvus® [vildagliptin]); Symlin® (pramlintide acetate).
Have had an organ transplant.
Have donated blood within 30 days of screening.
Have previously completed or withdrawn from this study or any other study investigating exenatide once weekly.
Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
Are currently participating in an interventional medical, surgical, or pharmaceutical study (a study in which an experimental, drug, medical, or surgical treatment is given). Patients completing the final visit of a study examining safety/efficacy of exenatide BID may enter this study on the same day if they meet other eligibility criteria.

Trial locations and contacts

26 sites in 5 countries.

Country

City, postcode or hospital

26 sites in 5 countries

United States11 sites

Research Site
Atlanta, Georgia
Research Site
Bowling Green, Kentucky
Research Site
Chattanooga, Tennessee
Research Site
Concord, California
Research Site
Corvallis, Oregon
Research Site
Fresno, California
Research Site
Idaho Falls, Idaho
Research Site
La Mesa, California
Research Site
Memphis, Tennessee
Research Site
Mesa, Arizona
Research Site
Tempe, Arizona

Other trials in United States

Romania6 sites

Research Site
Baia Mare
Research Site
Brasov
Research Site
Bucharesti
Research Site
Craiova
Research Site
Iași
Research Site
Suceava

Other trials in Romania

Canada4 sites

Research Site
Ajax, Ontario
Research Site
Cambridge, Ontario
Research Site
New Westminster, British Columbia
Research Site
Windsor, Ontario

Other trials in Canada

Mexico3 sites

Research Site
Chihuahua City, Chiuahua
Research Site
Distrito Federal
Research Site
Monterrey, Nuevo León

Other trials in Mexico

South Africa2 sites

Research Site
Johannesburg
Research Site
Pretoria

Other trials in South Africa

About this study

Conditions: Type 2 Diabetes
Being tested: exenatide
Keywords: Amylin, Lilly, exenatide once weekly, thiazolidinedione, metformin
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.

exenatideDrug
subcutaneous injection, 2.0mcg, once weekly

Study groups in NCT00753896
Study group	Role	What they receive
1	Experimental	Not described Receives: Drug: exenatide

What is being measured

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

Percentage of Patients Experiencing Adverse Events
Percentage of patients experiencing treatment-emergent adverse events over 52 weeks
Measured: Baseline to Week 52
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. Mean event rate = total number of events for all subjects in a treatment regimen / the total number of subject years of exposure for all subjects in that treatment. Standard error = square root of (total number of events / (subject years of exposure)**2).
Measured: Baseline to Week 52

Secondary outcomes (9)

Change in HbA1c From Baseline to Week 52
Change in HbA1c from baseline to endpoint
Measured: Baseline, Week 52
Percentage of Patients Achieving HbA1c <=7% at Week 52
Percentage of patients achieving HbA1c <=7% at endpoint (for patients with HbA1c >7% at baseline)
Measured: Baseline, Week 52
Percentage of Patients Achieving HbA1c <=6.5% at Week 52
Percentage of patients achieving HbA1c <=6.5% at endpoint (for patients with HbA1c >6.5% at baseline)
Measured: Baseline, Week 52
Change in Fasting Serum Glucose From Baseline to Week 52
Change in fasting serum glucose from baseline to endpoint
Measured: Baseline, Week 52
Change in Body Weight From Baseline to Week 52
Change in body weight from baseline to endpoint
Measured: Baseline, Week 52
Change in Total Cholesterol From Baseline to Week 52
Change in Total Cholesterol from baseline to endpoint
Measured: Baseline, Week 52
Change in High-density Lipoprotein (HDL) From Baseline to Week 52
Change in HDL from baseline to endpoint
Measured: Baseline, Week 52
Change in Triglycerides From Baseline to Week 52
Change in Triglycerides from baseline to endpoint
Measured: Baseline, Week 52
Change in Blood Pressure From Baseline to Week 52
Change in Systolic and Diastolic Blood Pressure from baseline to endpoint
Measured: Baseline, Week 52

Timeline

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

Oct 2008Nov 2009

First posted17 Sep 2008 (estimated)
Study startOct 2008
Primary completionJul 2009
Study completionNov 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 (1)Papers the sponsor has linked to this study.
Other trials for Type 2 DiabetesStudies 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 134 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00753896
Sponsor's protocol ID: H8O-MC-GWDC
Status last verified: Mar 2015
First submitted: 15 Sep 2008
Last updated: 21 Apr 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Norwood P, Liutkus JF, Haber H, Pintilei E, Boardman MK, Trautmann ME. Safety of exenatide once weekly in patients with type 2 diabetes mellitus treated with a thiazolidinedione alone or in combination with metformin for 2 years. Clin Ther. 2012 Oct;34(10):2082-90. doi: 10.1016/j.clinthera.2012.09.007. Epub 2012 Sep 29.
PubMed 23031623

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?

See locations

Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)

All Type 2 Diabetes trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Safety of Exenatide Once Weekly in Patients With Type 2 Diabetes Mellitus Treated With Thiazolidinedione Alone or Thiazolidinedione in Combination With Metformin
ClinicalTrials.gov ID: NCT00753896
Acronym / sponsor ID: H8O-MC-GWDC
Conditions: Type 2 Diabetes
Keywords: Amylin, Lilly, exenatide once weekly, thiazolidinedione, metformin
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 134 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Eli Lilly and Company
Study start: Oct 2008
Primary completion: Jul 2009 (actual)
Study completion: Nov 2009 (actual)
First posted: 17 Sep 2008 (estimated)
Results: Posted 20 Mar 2012

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: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
1	Experimental	Drug: exenatide

Who may qualify

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

Key inclusion criteria (12 listed)

Have type 2 diabetes
At least 18 years of age at screening.
Have HbA1c of 7.1% to 10.0%, inclusive, at screening.
Have a body mass index (BMI) of 25 kg/m2 to 45 kg/m2, inclusive.
Have been treated with a stable dose of TZD (≥4 mg/day rosiglitazone or ≥30 mg/day pioglitazone) for at least 120 days prior to Visit 1 OR Have been treated with a stable dose of TZD (≥4 mg/day rosiglitazone or ≥30 mg/day pioglitazone) for at least 120 days PLUS a stable dose of metformin for at least 90 days prior to Visit 1.

Key exclusion criteria (20 listed)

Have had a clinically significant history of cardiac disease or presence of active cardiac disease within the year prior to inclusion in the study, including myocardial infarction, clinically significant arrhythmia, unstable angina, coronary artery bypass surgery, angioplasty.
Is expected to require coronary artery bypass surgery or angioplasty during the course of the study.
Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis
Have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine ≥135 μmol/L for males and ≥110 μmol/L for females.
Have active or untreated malignancy, or have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years.

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
exenatidesubcutaneous injection, 2.0mcg, once weekly	Drug	1

Primary outcome

Percentage of Patients Experiencing Adverse Events
Time frame: Baseline to Week 52
Percentage of patients experiencing treatment-emergent adverse events over 52 weeks
Assessment of Event Rate of Treatment-Emergent Hypoglycemic Events
Time frame: Baseline to Week 52
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. Mean event rate = total number of events for all subjects in a treatment regimen / the total number of subject years of exposure for all subjects in that treatment. Standard error = square root of (total number of events / (subject years of exposure)**2).

9 secondary outcomes

Change in HbA1c From Baseline to Week 52
Time frame: Baseline, Week 52
Percentage of Patients Achieving HbA1c <=7% at Week 52
Time frame: Baseline, Week 52
Percentage of Patients Achieving HbA1c <=6.5% at Week 52
Time frame: Baseline, Week 52
Change in Fasting Serum Glucose From Baseline to Week 52
Time frame: Baseline, Week 52
Change in Body Weight From Baseline to Week 52
Time frame: Baseline, Week 52
Change in Total Cholesterol From Baseline to Week 52
Time frame: Baseline, Week 52
Change in High-density Lipoprotein (HDL) From Baseline to Week 52
Time frame: Baseline, Week 52
Change in Triglycerides From Baseline to Week 52
Time frame: Baseline, Week 52
Change in Blood Pressure From Baseline to Week 52
Time frame: Baseline, Week 52

Results and safety

Results posted to the registry on 20 Mar 2012, 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 Once Weekly	134	118

Primary outcome: Percentage of Patients Experiencing Adverse Events

Time frame: Baseline to Week 52. Number. Unit: percentage of patients

Measure	Exenatide Once Weekly n = 134
Value	73.1

Population analysed: All enrolled patients who had taken at least one dose of study drug. Sample size based on FDA recommendation for safety exposure: a minimum of 100 patients completing at least 52 weeks of treatment is sought to assess long-term safety associated with exposure to exenatide once weekly.

Primary outcome: Assessment of Event Rate of Treatment-Emergent Hypoglycemic Events

Time frame: Baseline to Week 52. Mean (Standard Error). Unit: events per subject-year

Measure	Exenatide Once Weekly n = 134
Major Hypoglycemia	0.00 (0.000)
Minor Hypoglycemia	0.02 (0.014)

9 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Exenatide Once Weekly	9 of 134 (6.7%)	67 of 134 (50%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 23031623Norwood P, Liutkus JF, Haber H, Pintilei E, Boardman MK, Trautmann ME. Safety of exenatide once weekly in patients with type 2 diabetes mellitus treated with a thiazolidinedione alone or in combination with metformin for 2 years. Clin Ther. 2012 Oct;34(10):2082-90. doi: 10.1016/j.clinthera.2012.09.007. Epub 2012 Sep 29.

Related trials for Type 2 Diabetes

Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)

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

26 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing exenatide in people with Type 2 Diabetes, run by AstraZeneca at 26 sites in 5 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 12 inclusion and 20 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 21 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 26 sites in United States, Romania, Canada, Mexico, South Africa. 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 20 Mar 2012). 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?

Percentage of Patients Experiencing Adverse Events (time frame: Baseline to Week 52). 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 NCT00753896, which also lists 1 linked publication.

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 21 Apr 2015.