{"protocolSection":{"identificationModule":{"nctId":"NCT00603239","orgStudyIdInfo":{"id":"H8O-MC-GWCG"},"organization":{"fullName":"AstraZeneca","class":"INDUSTRY"},"briefTitle":"Safety and Efficacy of Exenatide in Patients With Type 2 Diabetes Using a Thiazolidinedione or a Thiazolidinedione and Metformin","officialTitle":"Safety and Efficacy of Exenatide in Patients With Type 2 Diabetes Using a Thiazolidinedione or a Thiazolidinedione and Metformin"},"statusModule":{"statusVerifiedDate":"2015-03","overallStatus":"COMPLETED","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2008-01"},"primaryCompletionDateStruct":{"date":"2009-07","type":"ACTUAL"},"completionDateStruct":{"date":"2009-07","type":"ACTUAL"},"studyFirstSubmitDate":"2008-01-17","studyFirstSubmitQcDate":"2008-01-28","studyFirstPostDateStruct":{"date":"2008-01-29","type":"ESTIMATED"},"resultsFirstSubmitDate":"2010-07-20","resultsFirstSubmitQcDate":"2010-08-12","resultsFirstPostDateStruct":{"date":"2010-09-02","type":"ESTIMATED"},"lastUpdateSubmitDate":"2015-03-19","lastUpdatePostDateStruct":{"date":"2015-04-07","type":"ESTIMATED"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"SPONSOR"},"leadSponsor":{"name":"AstraZeneca","class":"INDUSTRY"},"collaborators":[{"name":"Eli Lilly and Company","class":"INDUSTRY"}]},"oversightModule":{"oversightHasDmc":false},"descriptionModule":{"briefSummary":"This study will assess safety and efficacy of exenatide in combination with a thiazolidinedione (TZD) and a TZD plus metformin over 26 weeks in adult patients with type 2 diabetes who have not achieved adequate glycemic control."},"conditionsModule":{"conditions":["Type 2 Diabetes Mellitus"],"keywords":["diabetes","exenatide","metformin","thiazolidinedione","Byetta","Amylin","Lilly"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE3"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"PARALLEL","primaryPurpose":"TREATMENT","maskingInfo":{"masking":"DOUBLE","whoMasked":["PARTICIPANT","INVESTIGATOR"]}},"enrollmentInfo":{"count":165,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"Exenatide twice daily (BID)","type":"EXPERIMENTAL","interventionNames":["Drug: exenatide"]},{"label":"Placebo","type":"PLACEBO_COMPARATOR","interventionNames":["Drug: placebo"]}],"interventions":[{"type":"DRUG","name":"exenatide","description":"subcutaneous injection, 5 mcg or 10 mcg, twice a day (BID)","armGroupLabels":["Exenatide twice daily (BID)"],"otherNames":["Byetta"]},{"type":"DRUG","name":"placebo","description":"subcutaneous injection, volume equivalent to 5 mcg or 10 mcg of active drug, twice a day","armGroupLabels":["Placebo"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Change in Glycosylated Hemoglobin (HbA1c)","description":"Change in HbA1c from baseline to endpoint after 26 weeks of treatment (i.e., HbA1c at endpoint minus HbA1c at baseline)","timeFrame":"baseline and 26 weeks"}],"secondaryOutcomes":[{"measure":"Percentage of Patients Achieving HbA1c <= 7%","description":"Percentage of intent-to-treat (ITT) patients who had HbA1c \\> 7% at baseline that decreased to \\<= 7% at endpoint (Week 26 or early discontinuation)","timeFrame":"26 weeks"},{"measure":"Percentage of Patients Achieving HbA1c <= 6.5%","description":"Percentage of ITT patients who had achieved HbA1c \\<= 6.5% at endpoint (Week 26 or early discontinuation)","timeFrame":"26 weeks"},{"measure":"Change in Fasting Serum Glucose (FSG)","description":"Change in FSG from baseline to endpoint (26 weeks)","timeFrame":"baseline and 26 weeks"},{"measure":"Change in Body Weight","description":"Change in body weight from baseline to endpoint (26 weeks)","timeFrame":"baseline and 26 weeks"},{"measure":"Change in Waist Circumference","description":"Change in waist circumference from baseline to endpoint (26 weeks)","timeFrame":"baseline and 26 weeks"},{"measure":"Change in Beta-cell Function","description":"Change in homeostatic model assessment-beta cell (HOMA-B) from baseline to endpoint (Week 26) (outcome measure is presented as the ratio of endpoint HOMA-B divided by baseline HOMA-B). HOMA-B is a measure of pancreatic beta-cell function.","timeFrame":"baseline and 26 weeks"},{"measure":"Change in Insulin Sensitivity.","description":"Change in homeostatic model assessment-insulin sensitivity (HOMA-S) from baseline to endpoint (26 weeks) (outcome measure is presented as the ratio of endpoint HOMA-S divided by baseline HOMA-S).","timeFrame":"baseline and 26 weeks"},{"measure":"Number of Subjects Who Experienced an Episode of Minor Hypoglycemia","description":"Overall number of subjects who experienced an episode of minor hypoglycemia.","timeFrame":"26 weeks"},{"measure":"Change in Impact of Weight on Quality of Life (IWQOL)-Lite Score","description":"IWQOL-Lite analysis of change from baseline to endpoint (26 weeks). IWQOL-Lite is a 31-item questionnaire, assessing the domains of physical function, self-esteem, sexual life, public distress, and work. Response categories for each item range from 1 = \"never true\" to 5 = \"always true.\"","timeFrame":"baseline and 26 weeks"},{"measure":"Change in Euroqol - 5 Domain Quality of Life (EQ-5D) Score","description":"EQ-5D Score - change from baseline to endpoint (26 weeks). EQ-5D is a 5-item questionnaire used to characterize current health states. The tool and accompanying visual analog scale (VAS) assess 5 domains of quality of life, including mobility, self-care, usual activity, pain, and anxiety/depression. Weights are used to score the responses to the 5 domains, with 3 options possible in each domain: extreme problems, some/moderate problems, or no problems. Scores range from 0 to 1, with a score of 1 representing a perfect health state.","timeFrame":"baseline and 26 weeks"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n* Diagnosed with type 2 diabetes\n* If treated with a thiazolidinedione (TZD) alone, the TZD dose must have been stable for at least 120 days\n* The dose of TZD must be: Rosiglitazone (≥4 mg/day) or pioglitazone (≥30 mg/day)\n* The metformin dose has been stable for at least 90 days\n* Have suboptimal glycemic control as evidenced by an HbA1c between 7.1% and 10.0%, inclusive.\n* Have a body mass index (BMI): 25 kg/m2 \\< BMI \\< 45 kg/m2.\n\nExclusion Criteria:\n\n* Have participated in this study previously or any other study using exenatide (AC2993/LY2148568) or glucagon-like peptide-1 (GLP-1) analogs, or have been previously treated with exenatide or GLP-1 analogs\n* 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 screening. This criterion includes drugs that have not received regulatory approval for any indication at the time of study entry.\n* Have been treated with exogenous insulin for more than 1 week within the 2 months prior to screening\n* Used drugs for weight loss (e.g., orlistat, rimonabant, sibutramine, or similar over-the-counter medications) within 3 months prior to screening.\n* Are currently treated with any of the following excluded medications:\n\n  * Sulfonylurea or meglitinide derivatives (e.g., repaglinide or nateglinide) within 3 months prior to screening\n  * Alpha-glucosidase inhibitor (e.g., miglitol or acarbose) within 3 months of screening\n  * Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g., sitagliptin or vildagliptin) within 3 months prior to screening\n  * Pramlintide acetate injection within 3 months prior to screening\n  * Drugs that directly affect gastrointestinal motility, including, but not limited to: Metoclopramide, cisapride, and chronic macrolide antibiotics\n  * 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","healthyVolunteers":false,"sex":"ALL","minimumAge":"18 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Chief Medical Officer, MD","affiliation":"Eli Lilly and Company","role":"STUDY_DIRECTOR"}],"locations":[{"facility":"Research Site","city":"Birmingham","state":"Alabama","country":"United States","geoPoint":{"lat":33.52066,"lon":-86.80249}},{"facility":"Research Site","city":"Concord","state":"California","country":"United States","geoPoint":{"lat":37.97798,"lon":-122.03107}},{"facility":"Research Site","city":"Fresno","state":"California","country":"United States","geoPoint":{"lat":36.74773,"lon":-119.77237}},{"facility":"Research Site","city":"Denver","state":"Colorado","country":"United States","geoPoint":{"lat":39.73915,"lon":-104.9847}},{"facility":"Research Site","city":"Las Vegas","state":"Nevada","country":"United States","geoPoint":{"lat":36.17497,"lon":-115.13722}},{"facility":"Research Site","city":"Mogadore","state":"Ohio","country":"United States","geoPoint":{"lat":41.04645,"lon":-81.39789}},{"facility":"Research Site","city":"Corvallis","state":"Oregon","country":"United States","geoPoint":{"lat":44.56457,"lon":-123.26204}},{"facility":"Research Site","city":"New Westminster","state":"British Columbia","country":"Canada","geoPoint":{"lat":49.20678,"lon":-122.91092}},{"facility":"Research Site","city":"Winnipeg","state":"Manitoba","country":"Canada","geoPoint":{"lat":49.8844,"lon":-97.14704}},{"facility":"Research Site","city":"Ajax","state":"Ontario","country":"Canada","geoPoint":{"lat":43.85012,"lon":-79.03288}},{"facility":"Research Site","city":"Cambridge","state":"Ontario","country":"Canada","geoPoint":{"lat":43.3601,"lon":-80.31269}},{"facility":"Research Site","city":"Windsor","state":"Ontario","country":"Canada","geoPoint":{"lat":42.30008,"lon":-83.01654}},{"facility":"Research Site","city":"Chihuahua City","state":"Chihuahua","country":"Mexico","geoPoint":{"lat":28.63528,"lon":-106.08889}},{"facility":"Research Site","city":"Celaya","state":"Guanajuato","country":"Mexico","geoPoint":{"lat":20.52181,"lon":-100.81399}},{"facility":"Research Site","city":"Mexico City","state":"Mexico City","country":"Mexico","geoPoint":{"lat":19.42847,"lon":-99.12766}},{"facility":"Research Site","city":"Monterrey","state":"Nuevo León","country":"Mexico","geoPoint":{"lat":25.68435,"lon":-100.31721}},{"facility":"Research Site","city":"Mexico City","country":"Mexico","geoPoint":{"lat":19.42847,"lon":-99.12766}},{"facility":"Research Site","city":"Baia Mare","country":"Romania","geoPoint":{"lat":47.65729,"lon":23.56808}},{"facility":"Research Site","city":"Brasov","country":"Romania","geoPoint":{"lat":45.64861,"lon":25.60613}},{"facility":"Research Site","city":"Bucharest","country":"Romania","geoPoint":{"lat":44.43225,"lon":26.10626}},{"facility":"Research Site","city":"Dolj","country":"Romania"},{"facility":"Research Site","city":"Iași","country":"Romania","geoPoint":{"lat":47.16667,"lon":27.6}},{"facility":"Research Site","city":"Suceava","country":"Romania","geoPoint":{"lat":47.63333,"lon":26.25}},{"facility":"Research Site","city":"Johannesburg","country":"South Africa","geoPoint":{"lat":-26.20227,"lon":28.04363}},{"facility":"Research Site","city":"Pretoria","country":"South Africa","geoPoint":{"lat":-25.74486,"lon":28.18783}}]},"referencesModule":{"references":[{"pmid":"20977576","type":"RESULT","citation":"Liutkus J, Rosas Guzman J, Norwood P, Pop L, Northrup J, Cao D, Trautmann M. A placebo-controlled trial of exenatide twice-daily added to thiazolidinediones alone or in combination with metformin. Diabetes Obes Metab. 2010 Dec;12(12):1058-65. doi: 10.1111/j.1463-1326.2010.01251.x."},{"pmid":"22913891","type":"DERIVED","citation":"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."}]}},"resultsSection":{"participantFlowModule":{"preAssignmentDetails":"A total of 165 patients, experiencing inadequate glycemic control using a thiazolidinedione (TZD) alone or in combination with metformin, following a 2-week placebo lead-in period, were randomly assigned in a proportion of 2:1 to add exenatide (111 patients) or placebo (54 patients) to their current therapy regimen.","groups":[{"id":"FG000","title":"Exenatide Twice Daily (BID)","description":"Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks"},{"id":"FG001","title":"Placebo","description":"Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks"}],"periods":[{"title":"Overall Study","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"111"},{"groupId":"FG001","numSubjects":"54"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"96"},{"groupId":"FG001","numSubjects":"50"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"15"},{"groupId":"FG001","numSubjects":"4"}]}],"dropWithdraws":[{"type":"Adverse Event","reasons":[{"groupId":"FG000","numSubjects":"4"},{"groupId":"FG001","numSubjects":"1"}]},{"type":"Entry criteria not met","reasons":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"1"}]},{"type":"Loss of glucose control","reasons":[{"groupId":"FG000","numSubjects":"3"},{"groupId":"FG001","numSubjects":"0"}]},{"type":"Lost to Follow-up","reasons":[{"groupId":"FG000","numSubjects":"2"},{"groupId":"FG001","numSubjects":"1"}]},{"type":"Physician Decision","reasons":[{"groupId":"FG000","numSubjects":"2"},{"groupId":"FG001","numSubjects":"0"}]},{"type":"Protocol Violation","reasons":[{"groupId":"FG000","numSubjects":"2"},{"groupId":"FG001","numSubjects":"0"}]},{"type":"Subject decision","reasons":[{"groupId":"FG000","numSubjects":"2"},{"groupId":"FG001","numSubjects":"1"}]}]}]},"baselineCharacteristicsModule":{"groups":[{"id":"BG000","title":"Exenatide Twice Daily (BID)","description":"Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks"},{"id":"BG001","title":"Placebo","description":"Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks"},{"id":"BG002","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"111"},{"groupId":"BG001","value":"54"},{"groupId":"BG002","value":"165"}]}],"measures":[{"title":"Age, Categorical","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"<=18 years","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Between 18 and 65 years","measurements":[{"groupId":"BG000","value":"97"},{"groupId":"BG001","value":"47"},{"groupId":"BG002","value":"144"}]},{"title":">=65 years","measurements":[{"groupId":"BG000","value":"14"},{"groupId":"BG001","value":"7"},{"groupId":"BG002","value":"21"}]}]}]},{"title":"Age, Continuous","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"54.93","spread":"8.27"},{"groupId":"BG001","value":"54.12","spread":"9.36"},{"groupId":"BG002","value":"54.67","spread":"8.62"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"44"},{"groupId":"BG001","value":"23"},{"groupId":"BG002","value":"67"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"67"},{"groupId":"BG001","value":"31"},{"groupId":"BG002","value":"98"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Change in Glycosylated Hemoglobin (HbA1c)","description":"Change in HbA1c from baseline to endpoint after 26 weeks of treatment (i.e., HbA1c at endpoint minus HbA1c at baseline)","populationDescription":"The number of participants was determined based on sample size calculations using parameter estimates from prior study H8O-MC-GWAP (NCT00099320), with change from baseline HbA1c as the primary efficacy measure. Primary analysis is reported for intent to treat population (ITT), last observation carried forward (LOCF).","reportingStatus":"POSTED","paramType":"LEAST_SQUARES_MEAN","dispersionType":"Standard Error","unitOfMeasure":"Percentage","timeFrame":"baseline and 26 weeks","groups":[{"id":"OG000","title":"Exenatide Twice Daily (BID)","description":"Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks"},{"id":"OG001","title":"Placebo","description":"Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"110"},{"groupId":"OG001","value":"54"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"-0.84","spread":"0.20"},{"groupId":"OG001","value":"-0.10","spread":"0.23"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"groupDescription":"Null hypothesis = Change from baseline in HbA1c is equal between the two treatment groups. Greater than 99% power to detect a difference between treatment groups of 0.88% in change in HbA1c from baseline using a 2-sided t-test at a significance level of 0.05.","testedNonInferiority":false,"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":"<0.001","pValueComment":"No adjustments were made (alpha = 0.05).","statisticalMethod":"ANCOVA","statisticalComment":"No adjustments for multiplicity were made.","ciPctValue":"95"}]},{"type":"SECONDARY","title":"Percentage of Patients Achieving HbA1c <= 7%","description":"Percentage of intent-to-treat (ITT) patients who had HbA1c \\> 7% at baseline that decreased to \\<= 7% at endpoint (Week 26 or early discontinuation)","populationDescription":"Based on primary efficacy sample size calculations. Analyses performed on ITT patient population.","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"percentage of participants","timeFrame":"26 weeks","groups":[{"id":"OG000","title":"Exenatide Twice Daily (BID)","description":"Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks"},{"id":"OG001","title":"Placebo","description":"Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"104"},{"groupId":"OG001","value":"52"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"49.0"},{"groupId":"OG001","value":"36.5"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"groupDescription":"Null hypothesis = Proportion of subjects with HbA1c \\<= 7% is equal between the two treatment groups.","testedNonInferiority":false,"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":"0.113","pValueComment":"No adjustments (alpha = 0.05).","statisticalMethod":"CMH test","statisticalComment":"No adjustment for multiplicity.","ciPctValue":"95"}]},{"type":"SECONDARY","title":"Percentage of Patients Achieving HbA1c <= 6.5%","description":"Percentage of ITT patients who had achieved HbA1c \\<= 6.5% at endpoint (Week 26 or early discontinuation)","populationDescription":"Based on primary efficacy sample size calculations. Analyses performed on ITT patient population.","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"percentage of participants","timeFrame":"26 weeks","groups":[{"id":"OG000","title":"Exenatide Twice Daily (BID)","description":"Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks"},{"id":"OG001","title":"Placebo","description":"Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"110"},{"groupId":"OG001","value":"54"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"33.6"},{"groupId":"OG001","value":"13.0"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"groupDescription":"Null hypothesis = Proportion of subjects achieving HbA1c \\<= 6.5% is equal between the two treatment groups.","testedNonInferiority":false,"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":"0.004","pValueComment":"No adjustments (alpha = 0.05).","statisticalMethod":"CMH test","statisticalComment":"No adjustment for multiplicity.","ciPctValue":"95"}]},{"type":"SECONDARY","title":"Change in Fasting Serum Glucose (FSG)","description":"Change in FSG from baseline to endpoint (26 weeks)","populationDescription":"Based on primary efficacy sample size calculations. Analyses performed on ITT patient population.","reportingStatus":"POSTED","paramType":"LEAST_SQUARES_MEAN","dispersionType":"Standard Error","unitOfMeasure":"mmol/L","timeFrame":"baseline and 26 weeks","groups":[{"id":"OG000","title":"Exenatide Twice Daily (BID)","description":"Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks"},{"id":"OG001","title":"Placebo","description":"Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"103"},{"groupId":"OG001","value":"53"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"-0.65","spread":"0.46"},{"groupId":"OG001","value":"0.37","spread":"0.52"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"groupDescription":"Null hypothesis = Change from baseline in FSG is equal between the two treatment groups.","testedNonInferiority":false,"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":"0.009","pValueComment":"No adjustments (alpha = 0.05).","statisticalMethod":"ANCOVA","statisticalComment":"No adjustment for multiplicity.","ciPctValue":"95"}]},{"type":"SECONDARY","title":"Change in Body Weight","description":"Change in body weight from baseline to endpoint (26 weeks)","populationDescription":"Based on primary efficacy sample size calculations. Analyses performed on ITT patient population.","reportingStatus":"POSTED","paramType":"LEAST_SQUARES_MEAN","dispersionType":"Standard Error","unitOfMeasure":"kg","timeFrame":"baseline and 26 weeks","groups":[{"id":"OG000","title":"Exenatide Twice Daily (BID)","description":"Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks"},{"id":"OG001","title":"Placebo","description":"Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"111"},{"groupId":"OG001","value":"54"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"-1.43","spread":"0.61"},{"groupId":"OG001","value":"-0.75","spread":"0.70"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"groupDescription":"Null hypothesis = Change from baseline to endpoint in body weight is equal between the two treatment groups.","testedNonInferiority":false,"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":"0.176","pValueComment":"No adjustments (alpha = 0.05).","statisticalMethod":"ANCOVA","statisticalComment":"No adjustment for multiplicity.","ciPctValue":"95"}]},{"type":"SECONDARY","title":"Change in Waist Circumference","description":"Change in waist circumference from baseline to endpoint (26 weeks)","populationDescription":"Based on primary efficacy sample size calculations. Analyses performed on ITT patient population.","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Deviation","unitOfMeasure":"cm","timeFrame":"baseline and 26 weeks","groups":[{"id":"OG000","title":"Exenatide Twice Daily (BID)","description":"Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks"},{"id":"OG001","title":"Placebo","description":"Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"109"},{"groupId":"OG001","value":"53"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"-2.26","spread":"3.83"},{"groupId":"OG001","value":"-1.85","spread":"3.75"}]}]}]},{"type":"SECONDARY","title":"Change in Beta-cell Function","description":"Change in homeostatic model assessment-beta cell (HOMA-B) from baseline to endpoint (Week 26) (outcome measure is presented as the ratio of endpoint HOMA-B divided by baseline HOMA-B). HOMA-B is a measure of pancreatic beta-cell function.","populationDescription":"Based on primary efficacy sample size calculations. Analyses performed on ITT patient population.","reportingStatus":"POSTED","paramType":"GEOMETRIC_MEAN","dispersionType":"Standard Error","unitOfMeasure":"ratio","timeFrame":"baseline and 26 weeks","groups":[{"id":"OG000","title":"Exenatide Twice Daily (BID)","description":"Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks"},{"id":"OG001","title":"Placebo","description":"Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"95"},{"groupId":"OG001","value":"49"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"1.08","spread":"0.12"},{"groupId":"OG001","value":"0.84","spread":"0.11"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"groupDescription":"Null hypothesis = Change form baseline in HOMA-B is equal between the two treatment groups.","testedNonInferiority":false,"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":"0.009","pValueComment":"No adjustments (alpha = 0.05).","statisticalMethod":"ANCOVA","statisticalComment":"No adjustment for multiplicity.","ciPctValue":"95"}]},{"type":"SECONDARY","title":"Change in Insulin Sensitivity.","description":"Change in homeostatic model assessment-insulin sensitivity (HOMA-S) from baseline to endpoint (26 weeks) (outcome measure is presented as the ratio of endpoint HOMA-S divided by baseline HOMA-S).","populationDescription":"Based on primary efficacy sample size calculations. Analyses performed on ITT patient population.","reportingStatus":"POSTED","paramType":"LEAST_SQUARES_MEAN","dispersionType":"Standard Error","unitOfMeasure":"ratio","timeFrame":"baseline and 26 weeks","groups":[{"id":"OG000","title":"Exenatide Twice Daily (BID)","description":"Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks"},{"id":"OG001","title":"Placebo","description":"Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"95"},{"groupId":"OG001","value":"49"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"1.09","spread":"0.11"},{"groupId":"OG001","value":"1.07","spread":"0.13"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"groupDescription":"Null hypothesis = Change from baseline in HOMA-S is equal between the two treatment groups.","testedNonInferiority":false,"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":"0.794","pValueComment":"No adjustments (alpha = 0.05).","statisticalMethod":"ANCOVA","statisticalComment":"No adjustment for multiplicity.","ciPctValue":"95"}]},{"type":"SECONDARY","title":"Number of Subjects Who Experienced an Episode of Minor Hypoglycemia","description":"Overall number of subjects who experienced an episode of minor hypoglycemia.","populationDescription":"Based on primary efficacy sample size calculations. Analyses performed on ITT patient population.","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"Participants","timeFrame":"26 weeks","groups":[{"id":"OG000","title":"Exenatide Twice Daily (BID)","description":"Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks"},{"id":"OG001","title":"Placebo","description":"Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"111"},{"groupId":"OG001","value":"54"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"4"},{"groupId":"OG001","value":"1"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"groupDescription":"Null hypothesis = Incidence of minor hypoglycemia episodes is equal between the two treatment groups.","testedNonInferiority":false,"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":"1.00","pValueComment":"No adjustments (alpha = 0.05).","statisticalMethod":"Fisher Exact","statisticalComment":"No adjustment for multiplicity.","ciPctValue":"95"}]},{"type":"SECONDARY","title":"Change in Impact of Weight on Quality of Life (IWQOL)-Lite Score","description":"IWQOL-Lite analysis of change from baseline to endpoint (26 weeks). IWQOL-Lite is a 31-item questionnaire, assessing the domains of physical function, self-esteem, sexual life, public distress, and work. Response categories for each item range from 1 = \"never true\" to 5 = \"always true.\"","populationDescription":"Based on primary efficacy sample size calculations. Analyses performed on ITT patient population.","reportingStatus":"POSTED","paramType":"LEAST_SQUARES_MEAN","dispersionType":"Standard Error","unitOfMeasure":"units on a scale","timeFrame":"baseline and 26 weeks","groups":[{"id":"OG000","title":"Exenatide Twice Daily (BID)","description":"Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks"},{"id":"OG001","title":"Placebo","description":"Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"108"},{"groupId":"OG001","value":"53"}]}],"classes":[{"title":"Change in Total Score","categories":[{"measurements":[{"groupId":"OG000","value":"-1.56","spread":"2.21"},{"groupId":"OG001","value":"0.11","spread":"2.49"}]}]},{"title":"Change in Physical Function component","categories":[{"measurements":[{"groupId":"OG000","value":"-3.84","spread":"3.06"},{"groupId":"OG001","value":"-1.05","spread":"3.43"}]}]},{"title":"Change in Self-Esteem component","categories":[{"measurements":[{"groupId":"OG000","value":"0.20","spread":"2.92"},{"groupId":"OG001","value":"-0.54","spread":"3.28"}]}]},{"title":"Change in Sexual Life component","categories":[{"measurements":[{"groupId":"OG000","value":"0.12","spread":"5.52"},{"groupId":"OG001","value":"5.01","spread":"6.12"}]}]},{"title":"Change in Public Distress component","categories":[{"measurements":[{"groupId":"OG000","value":"-0.48","spread":"2.61"},{"groupId":"OG001","value":"-0.28","spread":"2.92"}]}]},{"title":"Change in Work component","categories":[{"measurements":[{"groupId":"OG000","value":"-0.91","spread":"2.41"},{"groupId":"OG001","value":"0.08","spread":"2.71"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"groupDescription":"Null hypothesis = Change from baseline in IWQOL-Lite Total Score is equal between the two treatment groups. This statistical analysis is for the Total Score only.","testedNonInferiority":false,"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":"0.342","pValueComment":"No adjustments (alpha = 0.05).","statisticalMethod":"ANCOVA","statisticalComment":"No adjustment for multiplicity.","ciPctValue":"95"}]},{"type":"SECONDARY","title":"Change in Euroqol - 5 Domain Quality of Life (EQ-5D) Score","description":"EQ-5D Score - change from baseline to endpoint (26 weeks). EQ-5D is a 5-item questionnaire used to characterize current health states. The tool and accompanying visual analog scale (VAS) assess 5 domains of quality of life, including mobility, self-care, usual activity, pain, and anxiety/depression. Weights are used to score the responses to the 5 domains, with 3 options possible in each domain: extreme problems, some/moderate problems, or no problems. Scores range from 0 to 1, with a score of 1 representing a perfect health state.","populationDescription":"Based on primary efficacy sample size calculations. Analyses performed on ITT patient population.","reportingStatus":"POSTED","paramType":"LEAST_SQUARES_MEAN","dispersionType":"Standard Error","unitOfMeasure":"units on a scale","timeFrame":"baseline and 26 weeks","groups":[{"id":"OG000","title":"Exenatide Twice Daily (BID)","description":"Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks"},{"id":"OG001","title":"Placebo","description":"Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"108"},{"groupId":"OG001","value":"53"}]}],"classes":[{"title":"Change in Health State Score","categories":[{"measurements":[{"groupId":"OG000","value":"0.79","spread":"3.54"},{"groupId":"OG001","value":"-2.94","spread":"3.97"}]}]},{"title":"Change in Mobility component","categories":[{"measurements":[{"groupId":"OG000","value":"0.14","spread":"0.15"},{"groupId":"OG001","value":"0.15","spread":"0.17"}]}]},{"title":"Change in Self Care component","categories":[{"measurements":[{"groupId":"OG000","value":"0.08","spread":"0.14"},{"groupId":"OG001","value":"0.03","spread":"0.16"}]}]},{"title":"Change Usual Activities component","categories":[{"measurements":[{"groupId":"OG000","value":"0.17","spread":"0.15"},{"groupId":"OG001","value":"0.19","spread":"0.17"}]}]},{"title":"Change in Pain/Discomfort component","categories":[{"measurements":[{"groupId":"OG000","value":"0.29","spread":"0.16"},{"groupId":"OG001","value":"0.23","spread":"0.18"}]}]},{"title":"Change in Anxiety/Depression component","categories":[{"measurements":[{"groupId":"OG000","value":"-0.10","spread":"0.16"},{"groupId":"OG001","value":"-0.26","spread":"0.18"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"groupDescription":"Null hypothesis = Change from baseline in EQ-5D score is equal between the two treatment groups. This statistical analysis is for the EQ-5D Health State Score only.","testedNonInferiority":false,"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":"0.186","pValueComment":"No adjustments (alpha = 0.05)","statisticalMethod":"ANCOVA","statisticalComment":"No adjustment for multiplicity.","ciPctValue":"95"}]}]},"adverseEventsModule":{"frequencyThreshold":"5","timeFrame":"Adverse events were collected from baseline to endpoint, regardless of relationship to study drug. Events were captured as actual terms and coded to MedDRA,version 12.0.","eventGroups":[{"id":"EG000","title":"Exenatide Twice Daily (BID)","description":"Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 22 weeks","seriousNumAffected":1,"seriousNumAtRisk":111,"otherNumAffected":22,"otherNumAtRisk":111},{"id":"EG001","title":"Placebo","description":"Placebo equivalent volume to exenatide 5 mcg for 4 weeks, follwed by placebo equivalent volume to exenatide 10 mcg twice daily for 22 weeks","seriousNumAffected":0,"seriousNumAtRisk":54,"otherNumAffected":1,"otherNumAtRisk":54}],"seriousEvents":[{"term":"Ischaemic stroke","organSystem":"Nervous system disorders","sourceVocabulary":"MedDRA 12.0","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":111},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":54}]}],"otherEvents":[{"term":"Nausea","organSystem":"Gastrointestinal disorders","sourceVocabulary":"MedDRA 12.0","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":13,"numAtRisk":111},{"groupId":"EG001","numAffected":1,"numAtRisk":54}]},{"term":"Vomiting","organSystem":"Gastrointestinal disorders","sourceVocabulary":"MedDRA 12.0","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":9,"numAtRisk":111},{"groupId":"EG001","numAffected":0,"numAtRisk":54}]}]},"moreInfoModule":{"certainAgreement":{"piSponsorEmployee":false,"restrictionType":"GT60","restrictiveAgreement":true},"pointOfContact":{"title":"Peter Ohman, Medical Science Director","organization":"AstraZeneca","email":"ClinicalTrialTransparency@astrazeneca.com"}}},"derivedSection":{"miscInfoModule":{"versionHolder":"2026-10-09"},"conditionBrowseModule":{"meshes":[{"id":"D003924","term":"Diabetes Mellitus, Type 2"},{"id":"D003920","term":"Diabetes Mellitus"}],"ancestors":[{"id":"D044882","term":"Glucose Metabolism Disorders"},{"id":"D008659","term":"Metabolic Diseases"},{"id":"D009750","term":"Nutritional and Metabolic Diseases"},{"id":"D004700","term":"Endocrine System Diseases"}]},"interventionBrowseModule":{"meshes":[{"id":"D000077270","term":"Exenatide"}],"ancestors":[{"id":"D010455","term":"Peptides"},{"id":"D000602","term":"Amino Acids, Peptides, and Proteins"},{"id":"D014688","term":"Venoms"},{"id":"D045424","term":"Complex Mixtures"},{"id":"D014118","term":"Toxins, Biological"},{"id":"D001685","term":"Biological Factors"}]}},"hasResults":true}