Clinical trial NCT00082407: Exenatide Compared With Twice-Daily Biphasic Insulin Aspart in Patients With Type 2 Diabetes Using Sulfonylurea and Metformin
Official title: Efficacy of Exenatide (AC2993, Synthetic Exendin-4, LY2148568) Compared With Twice-Daily Biphasic Insulin Aspart in Patients With Type 2 Diabetes Using Sulfonylurea and Metformin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Keywords: diabetes
exendin
Amylin
Lilly
insulin aspart
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2004-05-10
Enrollment: 505
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 Phase 3, multicenter, open-label, comparator-controlled trial comparing the effect of exenatide twice daily to twice daily biphasic insulin aspart on glycemic control, as measured by hemoglobin A1c (HbA1c).


Eligibility criteria: Inclusion Criteria:

* Patients have been treated with a stable dose of the following for at least 3 months prior to screening: 1. \>=1500 mg/day immediate-release metformin or extended-release metformin and at least an optimally effective dose for brand of 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 11.0%, inclusive.
* Patients have a body mass index \>25kg/m2 and \<40 kg/m2.
* Female patients are not breastfeeding, and female patients of childbearing potential test negative for pregnancy, do not intend to become pregnant during the study, and agree to continue using a reliable method of birth control

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 previously, in this or any other study, received exenatide or glucagon-like peptide-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 have less than 5 years of remission history from any malignancy (other than basal cell or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate 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 biphasic insulin aspart, exenatide, or excipients contained in these agents.
* Patients have characteristics contraindicating metformin or sulfonylurea use, according to product-specific label.
* Patients have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine \>=1.5 mg/dL for males and \>=1.2 mg/dL for females.
* Patients have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransferase/serum glutamic pyruvic transaminase greater than three times the upper limit of the reference range.
* Patients have known hemoglobinopathy or chronic anemia.
* Patients have active proliferative retinopathy or macular edema.
* Patients are receiving treatment for gastrointestinal disease with a drug directly affecting gastrointestinal motility, including but not limited to metoclopramide, cisapride, and chronic macrolide antibiotics.
* 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 been treated for longer than 2 weeks with any of the following excluded medications within 3 months prior to screening: insulin, thiazolidinediones, alpha-glucosidase inhibitors, meglitinides.
* 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 Glcosylated Hemoglobin (HbA1c)
timeFrame: baseline, week 52
Secondary outcomes:
measure: Percentage of Patients Achieving HbA1c <=7%
timeFrame: 52 weeks
measure: Change in Body Weight
timeFrame: baseline, week 52
measure: Change in Fasting Serum Glucose
timeFrame: baseline, week 52
measure: Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
timeFrame: baseline, week 52
measure: Percentage of Patients With Hypoglycemic Events
timeFrame: 52 weeks
measure: Change in Rate of Hypoglycemic Events
timeFrame: baseline, week 52
Other outcomes:
Locations:
city: Osijek
country: Croatia
facility: Clinical Hospital Osijek
city: Zagreb
country: Croatia
facility: Klinica bolnica Dubrava
city: Zagreb
country: Croatia
facility: Klinicki bolnicki centar Zagreb-Rebro
city: Zagreb
country: Croatia
facility: Opca bolnica "Sveti Duh"
city: Augsburg
country: Germany
facility: Internistische Gemeinschaftspraxis
city: Beckum
country: Germany
facility: Dr. Karlheinz Hehemann
city: Dortmund
country: Germany
facility: Dr. Klaus Busch
city: Giessen
country: Germany
facility: Medical Clinic and Policlinic 3
city: Hamburg
country: Germany
facility: Diabetologische Schwerpunktpraxis
city: Mainz
country: Germany
facility: IKFE GmbH
city: Munich
country: Germany
facility: Institut for diabetic research
city: Neuss
country: Germany
facility: Profil, Institut fur Stoffwechselstorungen
city: Neuwied
country: Germany
facility: Dr. Thomas Behnke
city: Oschatz
country: Germany
facility: Dr. Bernd Donaubauer
city: Osnabruck
country: Germany
facility: Marienhospital Osnabruck
city: Schkeuditz
country: Germany
facility: Dr. Joerg Steindorf
city: Wiesbaden
country: Germany
facility: Dr. Jerzi Jasinski
city: Athens
country: Greece
facility: "Polyclinic" General Hospital of Athens
city: Athens
country: Greece
facility: Department of Endocrinology
city: Athens
country: Greece
facility: Diabetes Center
city: Patras
country: Greece
facility: University Hospital of Patras
city: Thessaloniki
country: Greece
facility: 1st Internal Medicine Department "Papagergiou"
city: Catania
country: Italy
facility: Instituto di Endocrinologia
city: Florence
country: Italy
facility: Dipartimento di fisiopatologia clinica
city: Milan
country: Italy
facility: U.O. Medicina Generale
city: Padova
country: Italy
facility: Ospedale Civile di Padova
city: Palermo
country: Italy
facility: Policlinico Univarsitario P. Giaccone
city: Torino
country: Italy
facility: U.O. Universita di Malattie del Metabolismo e Diabetologia
city: Apeldoorn
country: Netherlands
facility: Gelre Ziekenhuizen
city: Arnhem
country: Netherlands
facility: Rijnstate Ziekenhuis
city: Eindhoven
country: Netherlands
facility: Maxima Medisch Centrum Location Eindhoven
city: Coimbra
country: Portugal
facility: Hospitais da Universidade de Coimbra
city: Leiria
country: Portugal
facility: Hospital de Santo Andre
city: Lisboa
country: Portugal
facility: Associacao Protectora dos Diabeticos de Portugal
city: Matosinhos
country: Portugal
facility: Hospital Pedro Hispano
city: Brasov
country: Romania
facility: Spitalul Judetean Brasov
city: Bucuresti
country: Romania
facility: Institutul de Diabet
city: Judet Timis
country: Romania
facility: Spitalul Clinic nr. 1 Judetean
city: Moscow
country: Russian Federation
facility: National Endocrinology Research Center
city: Moscow
country: Russian Federation
facility: Setchenov Moscow Medical Academy
city: Moscow
country: Russian Federation
facility: Moscow State Medical Stomatological
city: Moscow
country: Russian Federation
facility: Russian Medical Academy for Advanced Medical Studies, Ministry of Health
city: St. Petersburg
country: Russian Federation
facility: Hospital of St. Elizabeth's
city: St. Petersburg
country: Russian Federation
facility: City Clinical Hospital #2
city: St. Petersburg
country: Russian Federation
facility: Medical Military Academy
city: Ljubljana
country: Slovenia
facility: Univerzitetni klinicni center Ljubljana
city: Maribor
country: Slovenia
facility: Splosna bolnisnica Maribor
city: Alicante
country: Spain
facility: Hospital Vega Baja
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Palma de Mallorca
country: Spain
facility: Endocrinology Service (Planta Baja)
city: Sevilla
country: Spain
facility: Hospital Virgen de Valme
city: Teruel
country: Spain
facility: Hospital General de Teruel
city: Valencia
country: Spain
facility: Hospital la Ribera Alzira
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Hualien
country: Taiwan
facility: Tzu Chi General Hospital
city: Taichung
country: Taiwan
facility: Veteran General Hospital-Taichung
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Birmingham
country: United Kingdom
facility: Diabetes Research, Ward 34, Birmingham Heartlands Hospital
city: Blackburn
country: United Kingdom
facility: Diabetes Unit, Blackburn Royal Infirmary
city: Colchester
country: United Kingdom
facility: Colchester General Hospital
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
city: Hull
country: United Kingdom
facility: The Michael White Center for Diabetes and Endocrinology
city: Liverpool
country: United Kingdom
facility: Clinical Sciences Centre
city: Middlesbrough
country: United Kingdom
facility: Education Centre, James Cook University Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Wellcome Labs, Royal Victoria Infirmary
city: Nottingham
country: United Kingdom
facility: Queens Medical Centre
city: Oxford
country: United Kingdom
facility: Diabetes Trial Unit OCDEM, Churchill Hospital
city: Wrexham
country: United Kingdom
facility: Diabetes Unit, Gladsone Centre, Maelor Hospital
Study officials:
affiliation: Eli Lilly and Company
name: Chief Medical Officer, MD
role: STUDY_DIRECTOR
References:
citation: Nauck MA, Duran S, Kim D, Johns D, Northrup J, Festa A, Brodows R, Trautmann M. A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study. Diabetologia. 2007 Feb;50(2):259-67. doi: 10.1007/s00125-006-0510-2. Epub 2006 Dec 8.
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.