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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00082381




Registration number
NCT00082381
Ethics application status
Date submitted
6/05/2004
Date registered
11/05/2004
Date last updated
7/04/2015

Titles & IDs
Public title
Effect of AC2993 Compared With Insulin Glargine in Patients With Type 2 Diabetes Also Using Combination Therapy With Sulfonylurea and Metformin
Scientific title
Effect of AC2993 (Synthetic Exendin-4) Compared With Insulin Glargine in Patients With Type 2 Diabetes Also Using Combination Therapy With Sulfonylurea and Metformin
Secondary ID [1] 0 0
H8O-MC-GWAA
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Type 2 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Exenatide (AC2993)
Treatment: Drugs - Insulin glargine

Experimental: Exenatide Arm - exenatide subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 22 weeks

Active comparator: Insulin Glargine Arm - subcutaneous injection, once daily; forced titration to target blood glucose level


Treatment: Drugs: Exenatide (AC2993)
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 22 weeks

Treatment: Drugs: Insulin glargine
subcutaneous injection, once daily; forced titration to target blood glucose level
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in Glycosylated Hemoglobin (HbA1c)
Timepoint [1] 0 0
Baseline, week 26
Secondary outcome [1] 0 0
Percentage of Patients Achieving HbA1c <=7%
Timepoint [1] 0 0
26 weeks
Secondary outcome [2] 0 0
Change in Body Weight
Timepoint [2] 0 0
Baseline, week 26
Secondary outcome [3] 0 0
Change in Fasting Serum Glucose
Timepoint [3] 0 0
Baseline, week 26
Secondary outcome [4] 0 0
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
Timepoint [4] 0 0
Baseline, week 26
Secondary outcome [5] 0 0
Percentage of Patients With Hypoglycemic Events
Timepoint [5] 0 0
26 weeks
Secondary outcome [6] 0 0
Change in Rate of Hypoglycemic Events
Timepoint [6] 0 0
Baseline, week 26

Eligibility
Key inclusion criteria
* Patients have been treated with a stable dose of one of the following for at least 3 months prior to screening: 1. 1500 to 2550 mg/day immediate-release metformin (or 1500 to 2000 mg/day extended-release metformin) and at least an optimally effective dose of a sulfonylurea, or 2. a fixed-dose sulfonylurea/metformin combination therapy with the same sulfonylurea and metformin requirements as for the individual components.
* HbA1c between 7.0% and 10.0%, inclusive.
* History of stable body weight (not varying by >10% for at least three months prior to screening).
* Female patients are not breastfeeding, and female patients of childbearing potential (not surgically sterilized and between menarche and 1-year postmenopause)
Minimum age
30 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patients are investigator site personnel directly affiliated with the study, or are immediate family of investigator site personnel directly affiliated with the study.
* Patients are employed by Lilly or Amylin.
* Patients have participated in this study previously or any other study using AC2993 or GLP-1 analogs.
* Patients have participated in an interventional medical, surgical, or pharmaceutical study within 30 days prior to screening. This criterion includes drugs that have not received regulatory approval for any indication at the time of study entry.
* Patients have had greater than three episodes of severe hypoglycemia within 6 months prior to screening.
* Patients are undergoing therapy for a malignancy, other than basal cell or squamous cell skin cancer.
* Patients have cardiac disease that is Class III or IV, according to the New York Heart Association criteria.
* Patients have a known allergy or hypersensitivity to insulin glargine, AC2993, or excipients contained in these agents.
* Patients have characteristics contraindicating metformin or sulfonylurea use, according to product-specific label, in the opinion of the investigator.
* Patients have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine >=1.5 mg/dL for males and >=1.3 mg/dL for females.
* Patients have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransferase/serum glutamicpyruvic transaminase greater than three times the upper limit of the reference range.
* Patients have known hemoglobinopathy or chronic anemia.
* Patients are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 weeks immediately prior to screening.
* Patients have used any prescription drug to promote weight loss within 3 months prior to screening.
* Patients have any other condition (including known drug or alcohol abuse or psychiatric disorder) that precludes them from following and completing the protocol, in the opinion of the investigator.
* Patients fail to satisfy the investigator of suitability to participate for any other reason.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2003
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2008
Sample size
Target
Accrual to date
Final
551
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Australian Clinical Research Centre - Miranda
Recruitment hospital [2] 0 0
Royal North Shore Hospital - St. Leonards
Recruitment hospital [3] 0 0
Clinical Trial and Research Unit - Wollongong
Recruitment hospital [4] 0 0
Royal Brisbane Hospital - Brisbane
Recruitment hospital [5] 0 0
Royal Adelaid Hospital - Adelaid
Recruitment hospital [6] 0 0
Repatriation General Hospital - Daw Park
Recruitment hospital [7] 0 0
SA Endocrine Clinical Research - Keswick
Recruitment hospital [8] 0 0
Eastern Health (Box Hill Hospital) - Box Hill
Recruitment hospital [9] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [10] 0 0
Freemantle Hospital - Freemantle
Recruitment postcode(s) [1] 0 0
2228 - Miranda
Recruitment postcode(s) [2] 0 0
2065 - St. Leonards
Recruitment postcode(s) [3] 0 0
2500 - Wollongong
Recruitment postcode(s) [4] 0 0
4029 - Brisbane
Recruitment postcode(s) [5] 0 0
5000 - Adelaid
Recruitment postcode(s) [6] 0 0
5041 - Daw Park
Recruitment postcode(s) [7] 0 0
5035 - Keswick
Recruitment postcode(s) [8] 0 0
3128 - Box Hill
Recruitment postcode(s) [9] 0 0
3050 - Parkville
Recruitment postcode(s) [10] 0 0
- Freemantle
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
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Florida
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Illinois
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United States of America
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Maryland
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United States of America
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Missouri
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Nevada
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New Hampshire
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New Mexico
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New York
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North Carolina
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Pennsylvania
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Tennessee
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Texas
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United States of America
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Utah
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United States of America
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Washington
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Belgium
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Endegem
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Belgium
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Gent
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Belgium
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Leuven
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Belgium
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Liege
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Belgium
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Merksem
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Belgium
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Sint Gillis Waas
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Brazil
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Curitiba
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Brazil
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Fortaleza
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Brazil
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Porto Alegre
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Finland
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Helsinki
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Finland
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Jyvaskyla
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Finland
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Oulu
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Germany
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Aschaffenburg
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Germany
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Bosenheim
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Germany
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Dortmund
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Germany
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Hamburg
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Germany
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Homburg/Saar
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Germany
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Mainz
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Germany
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Neuss
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Germany
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Neuwied
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Bilthoven
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Nieuwegein
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Stadskanaal
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Westeinde
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Bergen
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Jessheim
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Oslo
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Rud
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Norway
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Stravanger
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Poland
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Bydgoszcz
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Poland
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Czestochowa
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Poland
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Krakow
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Lodz
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Lublin
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Poland
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Mielec
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Poland
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Warszawa
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Portugal
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Almada
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Portugal
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Coimbra
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Portugal
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Lisboa
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Portugal
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Porto
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Puerto Rico
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Bayamon
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Manati
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Ponce
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Rio Piedras
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San Juan
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Yabucoa
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Spain
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Alicante
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Spain
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Madrid
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Spain
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Sevilla
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Spain
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Valencia
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Sweden
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Goteborg
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Sweden
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Helsingborg
Country [69] 0 0
Sweden
State/province [69] 0 0
Lund
Country [70] 0 0
Sweden
State/province [70] 0 0
Stockholm

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Eli Lilly and Company
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a multicenter, comparator-controlled, open-label, randomized, two-arm, parallel trial to compare the effect of exenatide twice daily and insulin glargine on glycemic control, as measured by hemoglobin A1c (HbA1c).
Trial website
https://clinicaltrials.gov/study/NCT00082381
Trial related presentations / publications
Heine RJ, Van Gaal LF, Johns D, Mihm MJ, Widel MH, Brodows RG; GWAA Study Group. Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med. 2005 Oct 18;143(8):559-69. doi: 10.7326/0003-4819-143-8-200510180-00006.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Chief Medical Officer, MD
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00082381