Effect of AC2993 Compared With Insulin Glargine in Patients With Type 2 Diabetes Also Using Combination Therapy With Sulfonylurea and Metformin

Diabetes Mellitus, Type 2 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00082381
• Other study ID #: H8O-MC-GWAA
• Status: Completed
• Phase: Phase 3
• First received: May 6, 2004
• Last updated: March 19, 2015
• Start date: June 2003
• Est. completion date: July 2008

Study information

• Verified date: March 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 551
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2

Intervention

Drug:
• Exenatide (AC2993)
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 22 weeks
• Insulin glargine
subcutaneous injection, once daily; forced titration to target blood glucose level

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Finland,  Germany,  Netherlands,  Norway,  Poland,  Portugal,  Puerto Rico,  Spain,  Sweden, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Glycosylated Hemoglobin (HbA1c)	Change in HbA1c from baseline to week 26	Baseline, week 26	No
Secondary	Percentage of Patients Achieving HbA1c <=7%	Percentage of patients in each arm who had HbA1c >7% at baseline and had HbA1c <=7% at week 26 (percentage = [number of subjects with HbA1c <=7% at week 26 divided by number of subjects with HbA1c >7% at baseline] * 100%).	26 weeks	No
Secondary	Change in Body Weight	Change in body weight from baseline to week 26	Baseline, week 26	No
Secondary	Change in Fasting Serum Glucose	Change in fasting serum glucose from baseline to week 26	Baseline, week 26	No
Secondary	Change in 7-point Self-monitored Blood Glucose (SMBG) Profile	Change in 7-point (pre-breakfast, 2 hour post breakfast, pre-lunch, 2 hour post lunch, pre-dinner, 2 hour post dinner, 0300 hours) SMBG profile from baseline to week 26	Baseline, week 26	No
Secondary	Percentage of Patients With Hypoglycemic Events	Percentage of patients who experienced at least one episode of hypoglycemia at any point during the 26 week Parent Study (incidence of hypoglycemia = number of patients who experienced at least one episode of hypoglycemia at any point during the 26 week Parent Study divided by the total number of patients who participated in the 26 week Parent Study	26 weeks	No
Secondary	Change in Rate of Hypoglycemic Events	Change in rate of hypoglycemic events per 30 days per patient from baseline to week 26	Baseline, week 26	No