Clinical trial NCT00082381: Effect of AC2993 Compared With Insulin Glargine in Patients With Type 2 Diabetes Also Using Combination Therapy With Sulfonylurea and Metformin
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Keywords: Diabetes
Insulin glargine
comparator
Amylin
Lilly
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2004-05-11
Enrollment: 551
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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)

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.

Primary outcomes:
measure: Change in Glycosylated Hemoglobin (HbA1c)
timeFrame: Baseline, week 26
Secondary outcomes:
measure: Percentage of Patients Achieving HbA1c <=7%
timeFrame: 26 weeks
measure: Change in Body Weight
timeFrame: Baseline, week 26
measure: Change in Fasting Serum Glucose
timeFrame: Baseline, week 26
measure: Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
timeFrame: Baseline, week 26
measure: Percentage of Patients With Hypoglycemic Events
timeFrame: 26 weeks
measure: Change in Rate of Hypoglycemic Events
timeFrame: Baseline, week 26
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Radiant Research-San Diego
state: California
city: San Mateo
country: United States
facility: Dorothy L. and James E. Frank Diabetes Research Institute
state: California
city: Fort Myers
country: United States
facility: Internal Medicine Associates Department of Research
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Miami
country: United States
facility: Baptist Diabetes Associates
state: Florida
city: West Palm Beach
country: United States
facility: Metabolic Research Institute, Inc.
state: Florida
city: Springfield
country: United States
facility: Springfield Diabetes & Endocrine Center
state: Illinois
city: Frederick
country: United States
facility: Frederick Primary Care Associates
state: Maryland
city: St. Louis
country: United States
facility: Radiant Research, Inc.
state: Missouri
city: Las Vegas
country: United States
facility: Lovelace Scientific Resources, Inc.
state: Nevada
city: Hampton
country: United States
facility: Diabetes, Endocrine & Nutrition
state: New Hampshire
city: Albuquerque
country: United States
facility: Lovelace Scientific Resources
state: New Mexico
city: Westfield
country: United States
facility: Great Lakes Medical Research
state: New York
city: Yonkers
country: United States
facility: DOCS, Beth Israel Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Piedmont Medical Research Associates
state: North Carolina
city: Philadelphia
country: United States
facility: Jon Shapiro, MD
state: Pennsylvania
city: Knoxville
country: United States
facility: Endocrinology Consultants of East Tennessee
state: Tennessee
city: Arlington
country: United States
facility: Israel Hartman, MD
state: Texas
city: San Antonio
country: United States
facility: Diabetes & Glandular Research Associates, P.A.
state: Texas
city: Ogden
country: United States
facility: Jack Wahlen, MD
state: Utah
city: Renton
country: United States
facility: Rainier Clinical Research Center, Inc.
state: Washington
city: Miranda
country: Australia
facility: Australian Clinical Research Centre
state: New South Wales
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Wollongong
country: Australia
facility: Clinical Trial and Research Unit
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Brisbane Hospital
state: Queensland
city: Adelaid
country: Australia
facility: Royal Adelaid Hospital
state: South Australia
city: Daw Park
country: Australia
facility: Repatriation General Hospital
state: South Australia
city: Keswick
country: Australia
facility: SA Endocrine Clinical Research
state: South Australia
city: Box Hill
country: Australia
facility: Eastern Health (Box Hill Hospital)
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Freemantle
country: Australia
facility: Freemantle Hospital
state: Western Australia
city: Endegem
country: Belgium
facility: UZ Antwerpen
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Gasthuisberg
city: Liege
country: Belgium
facility: CHU Sart Tilman
city: Merksem
country: Belgium
facility: A.Z. Jan Palfijn
city: Sint Gillis Waas
country: Belgium
facility: Sint Niklaasstraat
city: Curitiba
country: Brazil
facility: Hospital Nossa Senhora das Gracas
city: Fortaleza
country: Brazil
facility: Centro Integrado de Diabetes e Hipertensao
city: Fortaleza
country: Brazil
facility: Centro de Pesquisas em Diabetes e Doencas Endocrino Metabolicas/HUWC/UFC
city: Porto Alegre
country: Brazil
facility: Santa Casa de Misericordia de Porto Alegre
city: Helsinki
country: Finland
facility: Eiran Sairaala c/o9 Clires
city: Jyvaskyla
country: Finland
facility: Torikeskuksen Laakariasema, Yliopistonkatu
city: Oulu
country: Finland
facility: Oulu Deakoness Institution
city: Aschaffenburg
country: Germany
facility: Diabetologische Schwerpunktpraxis
city: Bosenheim
country: Germany
facility: Diabetologische Scherpunktpraxis
city: Dortmund
country: Germany
facility: Diabetologische Schwerpunktpraxis
city: Hamburg
country: Germany
facility: Krankenhaus Bethanien
city: Homburg/Saar
country: Germany
facility: Universitatskliniken des Saarlandes
city: Mainz
country: Germany
facility: IKFE GmbH
city: Neuss
country: Germany
facility: Profil Institut fur Stoffwechselforschung GmbH
city: Neuwied
country: Germany
facility: Diabetologische Schwerpunktpraxis
city: Bilthoven
country: Netherlands
facility: Diabetes Centrum Bilthoven
city: Brunssum
country: Netherlands
facility: Atrium Medisch Centrum Brunssum
city: Nieuwegein
country: Netherlands
facility: Sint Antonius Ziekenhuis Nieuwegein
city: Stadskanaal
country: Netherlands
facility: Refaja ziekenhuis
city: Westeinde
country: Netherlands
facility: Medisch Centrum
city: Bergen
country: Norway
facility: Markeveien Spesialistpraksis
city: Jessheim
country: Norway
facility: Spesiallegetjenesten AS
city: Oslo
country: Norway
facility: Betanien Spesialistsenter
city: Rud
country: Norway
facility: Sykehuset Asker of Baerum HF
city: Stravanger
country: Norway
facility: Forskningsstiftelsen Hjertelaget
city: Bydgoszcz
country: Poland
facility: Bydgoskie Centrum Diabetologii i Endokrynologii
city: Czestochowa
country: Poland
facility: Oddzial Chorob Wewnetrznych
city: Krakow
country: Poland
facility: NZOZ "Diab-Endo-Met"
city: Lodz
country: Poland
facility: Poradnia Diabetologiczna
city: Lublin
country: Poland
facility: Poradnia Diabetologiczna
city: Mielec
country: Poland
facility: Oddzial Chorob Wewnetrznych
city: Warszawa
country: Poland
facility: Oddzial Chorob Wewnetrznych i Diabetologii
city: Warszawa
country: Poland
facility: Wojewodzka Poradnia dla Chorych na Cukrzyce
city: Almada
country: Portugal
facility: Hospital Garcia de Orta-Servico de Endocrinologia
city: Coimbra
country: Portugal
facility: Centro Hospitalar de Coimbra
city: Lisboa
country: Portugal
facility: Associacao Protectora dos Diabeticos de Portugal
city: Porto
country: Portugal
facility: Hospital Geral de Santo Antonio
city: Bayamon
country: Puerto Rico
facility: Universidad Central del Caribe
city: Manati
country: Puerto Rico
facility: Hospital Alejandro Otero Lopez
city: Ponce
country: Puerto Rico
facility: Dr. Luis Ruiz
city: Rio Piedras
country: Puerto Rico
facility: RCMI-Clinical Research Center
city: San Juan
country: Puerto Rico
facility: San Juan Health Center
city: Yabucoa
country: Puerto Rico
facility: Centro de Endocrinologia del Este
city: Alicante
country: Spain
facility: Hospital Vega Baja
city: Madrid
country: Spain
facility: Hospital Doce de Octubre
city: Madrid
country: Spain
facility: Hospital Gral de Mostoles
city: Sevilla
country: Spain
facility: Hospital Virgen de Valme
city: Valencia
country: Spain
facility: Hospital la Ribera, Alzira
city: Goteborg
country: Sweden
facility: Lundberglaboratoriet for diabetesforskning
city: Helsingborg
country: Sweden
facility: Medicinska kliniken
city: Lund
country: Sweden
facility: Kliniska Forskningsenheren
city: Stockholm
country: Sweden
facility: Diabetesmottagningen, Intermedicinska kliniken
city: Stockholm
country: Sweden
facility: CME, M71
city: Stockholm
country: Sweden
facility: Enheten for metabol kontroll
Study officials:
affiliation: Eli Lilly and Company
name: Chief Medical Officer, MD
role: STUDY_DIRECTOR
References:
citation: 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.
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.
citation: 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.