Diabetes Mellitus, Type 2Phase 3NCT00135330
An Evaluation of Exenatide and Rosiglitazone in Subjects With Type 2 Diabetes Mellitus
A Phase 3 study testing exenatide and rosiglitazone in people with Diabetes Mellitus, Type 2, run by AstraZeneca at 19 sites in United States.
Trial summary
This protocol is designed to evaluate the metabolic effects of adding exenatide, rosiglitazone, or both to an existing regimen of metformin in subjects with inadequate glycemic control. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- exenatide and rosiglitazone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 137 participants
- Where
- 19 sitesUnited States
- Study dates
- Oct 2005to Jul 2008
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HbA1c of 6.8% to 10.0%, inclusive.
- Body mass index (BMI) of 25 kg/m^2 to 40 kg/m^2, inclusive.
Who cannot join
- Have participated in this study previously, or have received exenatide, pramlintide acetate, GLP-1 analogs, or dipeptidyl peptidase-IV (DPP-IV) inhibitors
- Have participated in an interventional, medical, surgical, or pharmaceutical study (a study in which an experimental, drug, medical, or surgical treatment was given) within 30 days of study start. This criterion includes drugs that have not received regulatory approval for any indication at the time of study start.
- Treated with any of the following medications:
- Thiazolidinedione within 5 months of screening;
- Sulfonylurea within 3 months of screening;
- Metformin/sulfonylurea combination therapy within 3 months of screening;
Show all 16Show fewer
- Alpha-glucosidase inhibitor within 3 months of screening;
- Meglitinide within 3 months of screening;
- Insulin for more than 1 week within the 3 months prior to screening.
- Symlin (pramlintide acetate) injection or Byetta (exenatide) injection at any time
- Chronic (more than 2 weeks) or recent (within 4 weeks of study start) use of a drug that directly affects gastrointestinal motility
- Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within the 4 weeks immediately preceding study start
- Regular use of a medication with addictive potential such as an opiate, narcotic, or tranquilizer
- Systemic antineoplastic agent
- Systemic transplantation medication
- Drugs for weight loss, including over-the-counter medications, within the 4 months prior to study start
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
United States19 sites
Research Site
Atlanta, Georgia
Research Site
Boston, Massachusetts
Research Site
Cincinnati, Ohio
Research Site
Honolulu, Hawaii
Research Site
Indianapolis, Indiana
Research Site
Jacksonville, Florida
Research Site
League City, Texas
Research Site
Minneapolis, Minnesota
Research Site
New Braunfels, Texas
Research Site
Orlando, Florida
Research Site
Phoenix, Arizona
Research Site
Pittsfield, Massachusetts
Research Site
Renton, Washington
Research Site
Rochester, Minnesota
Research Site
San Antonio, Texas
Research Site
San Francisco, California
Research Site
Spokane, Washington
Research Site
Syracuse, New York
Research Site
The Bronx, New York
About this study
Official title: An Evaluation of the Metabolic Effects of Exenatide, Rosiglitazone, and Exenatide Plus Rosiglitazone in Subjects With Type 2 Diabetes Mellitus Treated With Metformin
This protocol is designed to evaluate the metabolic effects of adding exenatide, rosiglitazone, or both to an existing regimen of metformin in subjects with inadequate glycemic control.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- exenatide, rosiglitazone
- Keywords
- diabetes, exenatide, rosiglitazone, 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.
exenatideDrug
Also called Byetta
subcutaneous injection, 5mcg or 10mcg, twice a day
rosiglitazoneDrug
Also called Avandia
oral tablet, 2mg or 4mg, twice a day
| Study group | Role | What they receive |
|---|---|---|
| Exenatide Arm | Experimental | Not described Receives: Drug: exenatide |
| Exenatide plus Rosiglitazone Arm | Experimental | Not described Receives: Drug: exenatide; Drug: rosiglitazone |
| Rosiglitazone Arm | Experimental | Not described Receives: Drug: rosiglitazone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in ASIiAUC During a Hyperglycemic Clamp Test.
Change in insulin incremental area under the concentration-time curve (ASIiAUC) from baseline to week 20. ASIiAUC is a measure of beta-cell function.
Measured: 20 weeks
Secondary outcomes (28)
Change in AUC for Glucose During a Meal Challenge Test (MCT).
Change in AUC(15-180 min) for glucose during a MCT baseline to week 20.
Measured: Week 20
Change in Insulin Sensitivity Index as Measured by M-value.
Change of M-Value (mg/kg-min) during hyperinsulinemic euglycemic clamp test from baseline to week 20.
Measured: Week 20
Change in Insulin AUC in the First Stage From Baseline to Endpoint.
Change in insulin AUC in the first stage(uIU-min/ml) from baseline to week 20. "First stage" represents the first 10 minutes after reaching a steady state during a hyperglycemic clamp test.
Measured: Week 20
Change in Insulin iAUC From Baseline to Endpoint.
Change in insulin iAUC in the first stage(uIU-min/ml) from baseline to week 20. "First stage" represents the first 10 minutes after reaching a steady state during a hyperglycemic clamp test.
Measured: Week 20
Ratio (Value at Endpoint Divided by Value at Baseline) of AUC for Insulin During a Meal Challenge Test (MCT).
Ratio (value at endpoint divided by value at baseline) of AUC (15-180 min) for insulin (uIU-min/ml) during MCT.
Measured: Week 20
Change in AUC for C-peptide During a Meal Challenge Test (MCT).
Ratio (value at endpoint divided by value at baseline) of AUC(15-180 min) for C-peptide (nmol-min/L) during a MCT from baseline to week 20.
Measured: Week 20
Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT).
Change in incremental for postprandial glucose (mmol/L) during a MCT from baseline to week 20.
Measured: Week 20
Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT).
Change in incremental for postprandial insulin (mmol/L) during meal challenge test (MCT) from baseline to week 20.
Measured: Week 20
Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT).
Change in incremental for postprandial C-peptide (mmol/L) during MCT from baseline to week 20.
Measured: Week 20
Change in HbA1c
Change in HbA1c from baseline to week 20.
Measured: Week 20
Change in Fasting Serum Glucose Concentration.
Change in fasting serum glucose concentration from baseline to week 20.
Measured: Week 20
Change in Fasting C-peptide
Change in fasting C-peptide from baseline to week 20.
Measured: Week 20
Change in Fasting Insulin
Change in fasting insulin from baseline to week 20.
Measured: Week 20
Change in Fasting Proinsulin
Ratio (endpoint value divided by baseline value) for fasting proinsulin, comparing endpoint (week 20) to baseline
Measured: Week 20
Change in Body Weight
Change in body weight from baseline to week 20.
Measured: Week 20
Change in Fasting Total Cholesterol.
Change in fasting total cholestrol from baseline to week 20.
Measured: Week 20
Change in Fasting HDL Cholesterol
Change in fasting high-density lipoprotein (HDL) cholesterol from baseline to week 20.
Measured: Week 20
Change in Fasting LDL Cholesterol
Change in fasting low-density lipoprotein (LDL) cholesterol from baseline to week 20.
Measured: Week 20
Change in Fasting Triglycerides
Ratio (endpint value divided by baseline value) of fasting triglycerides from baseline to week 20.
Measured: Week 20
Change in Percent Body Fat During a Meal Challenge Test (MCT)
Change in percent body fat from baseline to week 20, as assessed during an MCT
Measured: 20 weeks
Change in Body Fat Mass During a Meal Challenge Test (MCT)
Change in body fat mass form baseline to week 20, as assessed during an MCT
Measured: 20 weeks
Change in Lean Body Mass During a Meal Challenge Test (MCT)
Change in lean body mass from baseline to week 20, as assessed during an MCT
Measured: 20 weeks
Change in Waist Circumference
Change in waist circumference from baseline to week 20
Measured: 20 weeks
Change in Hip Circumference
Change in hip circumference form baseline to week 20
Measured: 20 weeks
Change in Waist-to-hip Ratio
Change in waist-to-hip ratio (waist circumference divided by hip circumference) from baseline to week 20
Measured: 20 weeks
Incidence of Hypoglycemia Events
Number of subjects experiencing hypoglycemia at any point during the study
Measured: 20 weeks
Hypoglycemia Rate Per 30 Days Per Patient
Average number of episodes of hypoglycemia per 30 days per patient
Measured: 20 weeks
Pedal Edema Score
Pedal edema scores experienced by each patient throughout the study ("1+" indicates a patient experienced a pedal edema score of 1 , 2, or 3; "2+" indicates a patient experienced a pedal edema score of 2 or 3, etc.)
Scale:
- Slight pitting, no visible distortion, disappears rapidly
- A somewhat deeper pit than in 1+, but again no readily detectable distortion, and it disappears in 10 - 15 seconds
- The pit is noticeably deep and may last more than a minute; the dependent extremity looks fuller and swollen
- The pit is very deep, lasts as long as 2 - 5 minutes, and the dependent extremity is grossly distorted
Measured: 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2005 (estimated)
- Study startOct 2005
- Primary completionJul 2008
- Study completionJul 2008
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 Diabetes Mellitus, Type 2Studies 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
- 137 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Eli Lilly and Company
- Responsible party
- Sponsor
- Investigators
- James Malone, MD, Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00135330
- Sponsor's protocol ID
- H8O-US-GWAY
- Status last verified
- Mar 2015
- First submitted
- 24 Aug 2005
- Last updated
- 7 Apr 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Fineman MS, Mace KF, Diamant M, Darsow T, Cirincione BB, Booker Porter TK, Kinninger LA, Trautmann ME. Clinical relevance of anti-exenatide antibodies: safety, efficacy and cross-reactivity with long-term treatment. Diabetes Obes Metab. 2012 Jun;14(6):546-54. doi: 10.1111/j.1463-1326.2012.01561.x. Epub 2012 Feb 10.
PubMed 22236356DeFronzo RA, Triplitt C, Qu Y, Lewis MS, Maggs D, Glass LC. Effects of exenatide plus rosiglitazone on beta-cell function and insulin sensitivity in subjects with type 2 diabetes on metformin. Diabetes Care. 2010 May;33(5):951-7. doi: 10.2337/dc09-1521. Epub 2010 Jan 27.
PubMed 20107105
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
- An Evaluation of the Metabolic Effects of Exenatide, Rosiglitazone, and Exenatide Plus Rosiglitazone in Subjects With Type 2 Diabetes Mellitus Treated With Metformin
- ClinicalTrials.gov ID
- NCT00135330
- Acronym / sponsor ID
- H8O-US-GWAY
- Conditions
- Diabetes Mellitus, Type 2
- Keywords
- diabetes, exenatide, rosiglitazone, Amylin, Lilly
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 137 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Eli Lilly and Company
- Study start
- Oct 2005
- Primary completion
- Jul 2008 (actual)
- Study completion
- Jul 2008 (actual)
- First posted
- 26 Aug 2005 (estimated)
- Results
- Posted 28 Aug 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This protocol is designed to evaluate the metabolic effects of adding exenatide, rosiglitazone, or both to an existing regimen of metformin in subjects with inadequate glycemic control.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Exenatide Arm | Experimental | Drug: exenatide |
| Exenatide plus Rosiglitazone Arm | Experimental | Drug: exenatide, Drug: rosiglitazone |
| Rosiglitazone Arm | Experimental | Drug: rosiglitazone |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- HbA1c of 6.8% to 10.0%, inclusive.
- Body mass index (BMI) of 25 kg/m^2 to 40 kg/m^2, inclusive.
Key exclusion criteria (16 listed)
- Have participated in this study previously, or have received exenatide, pramlintide acetate, GLP-1 analogs, or dipeptidyl peptidase-IV (DPP-IV) inhibitors
- Have participated in an interventional, medical, surgical, or pharmaceutical study (a study in which an experimental, drug, medical, or surgical treatment was given) within 30 days of study start. This criterion includes drugs that have not received regulatory approval for any indication at the time of study start.
- Treated with any of the following medications:
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 |
|---|---|---|
| exenatideAlso: Byettasubcutaneous injection, 5mcg or 10mcg, twice a day | Drug | Exenatide Arm, Exenatide plus Rosiglitazone Arm |
| rosiglitazoneAlso: Avandiaoral tablet, 2mg or 4mg, twice a day | Drug | Exenatide plus Rosiglitazone Arm, Rosiglitazone Arm |
Primary outcome
Change in ASIiAUC During a Hyperglycemic Clamp Test.
Time frame: 20 weeks
Change in insulin incremental area under the concentration-time curve (ASIiAUC) from baseline to week 20. ASIiAUC is a measure of beta-cell function.
28 secondary outcomes
Change in AUC for Glucose During a Meal Challenge Test (MCT).
Time frame: Week 20
Change in Insulin Sensitivity Index as Measured by M-value.
Time frame: Week 20
Change in Insulin AUC in the First Stage From Baseline to Endpoint.
Time frame: Week 20
Change in Insulin iAUC From Baseline to Endpoint.
Time frame: Week 20
Ratio (Value at Endpoint Divided by Value at Baseline) of AUC for Insulin During a Meal Challenge Test (MCT).
Time frame: Week 20
Change in AUC for C-peptide During a Meal Challenge Test (MCT).
Time frame: Week 20
Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT).
Time frame: Week 20
Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT).
Time frame: Week 20
Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT).
Time frame: Week 20
Change in HbA1c
Time frame: Week 20
Change in Fasting Serum Glucose Concentration.
Time frame: Week 20
Change in Fasting C-peptide
Time frame: Week 20
Change in Fasting Insulin
Time frame: Week 20
Change in Fasting Proinsulin
Time frame: Week 20
Change in Body Weight
Time frame: Week 20
Change in Fasting Total Cholesterol.
Time frame: Week 20
Change in Fasting HDL Cholesterol
Time frame: Week 20
Change in Fasting LDL Cholesterol
Time frame: Week 20
Change in Fasting Triglycerides
Time frame: Week 20
Change in Percent Body Fat During a Meal Challenge Test (MCT)
Time frame: 20 weeks
Change in Body Fat Mass During a Meal Challenge Test (MCT)
Time frame: 20 weeks
Change in Lean Body Mass During a Meal Challenge Test (MCT)
Time frame: 20 weeks
Change in Waist Circumference
Time frame: 20 weeks
Change in Hip Circumference
Time frame: 20 weeks
Change in Waist-to-hip Ratio
Time frame: 20 weeks
Incidence of Hypoglycemia Events
Time frame: 20 weeks
Hypoglycemia Rate Per 30 Days Per Patient
Time frame: 20 weeks
Pedal Edema Score
Time frame: 20 weeks
Results and safety
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 22236356Fineman MS, Mace KF, Diamant M, Darsow T, Cirincione BB, Booker Porter TK, Kinninger LA, Trautmann ME. Clinical relevance of anti-exenatide antibodies: safety, efficacy and cross-reactivity with long-term treatment. Diabetes Obes Metab. 2012 Jun;14(6):546-54. doi: 10.1111/j.1463-1326.2012.01561.x. Epub 2012 Feb 10.
- Derived from this study: PubMed 20107105DeFronzo RA, Triplitt C, Qu Y, Lewis MS, Maggs D, Glass LC. Effects of exenatide plus rosiglitazone on beta-cell function and insulin sensitivity in subjects with type 2 diabetes on metformin. Diabetes Care. 2010 May;33(5):951-7. doi: 10.2337/dc09-1521. Epub 2010 Jan 27.
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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.
James Malone, MD study director
Eli Lilly and Company
19 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 and rosiglitazone in people with Diabetes Mellitus, Type 2, run by AstraZeneca at 19 sites in United States.
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 2 inclusion and 16 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 19 sites in United States. 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 28 Aug 2009). 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 ASIiAUC During a Hyperglycemic Clamp Test. (time frame: 20 weeks). 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 NCT00135330, 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.