Clinical trial NCT02229396: Phase 3 28-Week Study With 24-Week and 52-week Extension Phases to Evaluate Efficacy and Safety of Exenatide Once Weekly and Dapagliflozin Versus Exenatide and Dapagliflozin Matching Placebo
Official title: A 28-week, Multicenter, Randomized, Double-Blind, Active-Controlled, Phase 3 Study With a 24-week Extension Phase Followed by a 52-week Extension Phase to Evaluate the Efficacy and Safety of Simultaneous Administration of Exenatide Once Weekly 2 mg and Dapagliflozin Once Daily 10 mg Compared to Exenatide Once Weekly 2 mg Alone and Dapagliflozin Once Daily 10 mg Alone in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus
Keywords: Diabetes Mellitus
Exenatide
Dapagliflozin
Diabetes medication
Treatment efficacy
Placebo
Metabolism
Cardiovascular metabolic
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2014-09-01
Enrollment: 695
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study D5553C0003 is a 28-week, randomized, double-blind, active-controlled, multicenter, Phase 3 efficacy and safety study with 24-week and 52-week extension phases of simultaneous administration of exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg once daily (QD) compared to EQW 2 mg alone and dapagliflozin 10 mg QD alone in patients with Type 2 diabetes who have inadequate glycemic control on metformin.


Eligibility criteria: Inclusion criteria

* Has a diagnosis of T2DM.
* Has HbA1c of 8.0% to 12.0%, inclusive, at Visit 1 and Visit 2.
* Treated with a stable dose of metformin ≥1500 mg/day for at least 2 months prior to Screening.

Exclusion criteria

* FPG ≥280 mg/dL (15.6 mmol/L).
* Serum calcitonin concentration ≥40 pg/mL (≥40 ng/L) at Visit 1 (Screening)
* Clinically significant abnormal free T4 values or patients needing initiation or adjustment of thyroid treatment according to the investigator.
* Abnormal thyroid stimulating hormone (TSH) value at Screening will be further evaluated by free T4.Patients with clinically significant abnormal free T4 values will be excluded.
* Known active proliferative retinopathy.
* History of, or currently have, acute or chronic pancreatitis, or have triglyceride concentrations ≥500 mg/dL (≥5.65 mmol/L) at Visit 1
* History or presence of inflammatory bowel disease or other severe GI diseases, particularly those which may impact gastric emptying, such as gastroparesis or pyloric stenosis.
* History of gastric bypass surgery or gastric banding surgery, or either procedure is planned during the time period of the study. Current use of gastric balloons is also excluded.

Primary outcomes:
measure: Change in HbA1c From Baseline to Week 28
timeFrame: Baseline to Week 28
Secondary outcomes:
measure: Change in Body Weight From Baseline to Week 28
timeFrame: Baseline to Week 28
measure: Change in Fasting Plasma Glucose From Baseline to Week 28
timeFrame: Baseline to Week 28
measure: Change From Baseline to Week 28 in 2-hour Postprandial Glucose After a Standard Meal Tolerance Test
timeFrame: Baseline to Week 28
measure: Percentage of Patients Achieving Weight Loss ≥5.0% at Week 28
timeFrame: Baseline to Week 28
measure: Change in Fasting Plasma Glucose From Baseline to Week 2
timeFrame: Baseline to Week 2
measure: Percentage of Patients Achieving HbA1c <7% at Week 28
timeFrame: Baseline to Week 28
measure: Change in Systolic Blood Pressure From Baseline to Week 28
timeFrame: Baseline to Week 28
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Huntsville
country: United States
facility: Research Site
state: Alabama
city: Tuscumbia
country: United States
facility: Research Site
state: Alabama
city: Glendale
country: United States
facility: Research Site
state: Arizona
city: Tempe
country: United States
facility: Research Site
state: Arizona
city: Anaheim
country: United States
facility: Research Site
state: California
city: Chula Vista
country: United States
facility: Research Site
state: California
city: El Cajon
country: United States
facility: Research Site
state: California
city: Fresno
country: United States
facility: Research Site
state: California
city: La Mesa
country: United States
facility: Research Site
state: California
city: Long Beach
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Mission Hills
country: United States
facility: Research Site
state: California
city: Montclair
country: United States
facility: Research Site
state: California
city: Oceanside
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: Tustin
country: United States
facility: Research Site
state: California
city: Van Nuys
country: United States
facility: Research Site
state: California
city: Boynton Beach
country: United States
facility: Research Site
state: Florida
city: Clearwater
country: United States
facility: Research Site
state: Florida
city: Coral Gables
country: United States
facility: Research Site
state: Florida
city: Fort Lauderdale
country: United States
facility: Research Site
state: Florida
city: Hialeah
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: North Miami Beach
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Williston
country: United States
facility: Research Site
state: Florida
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Avon
country: United States
facility: Research Site
state: Indiana
city: Evansville
country: United States
facility: Research Site
state: Indiana
city: Franklin
country: United States
facility: Research Site
state: Indiana
city: Muncie
country: United States
facility: Research Site
state: Indiana
city: Newton
country: United States
facility: Research Site
state: Kansas
city: Monroe
country: United States
facility: Research Site
state: Louisiana
city: Hazelwood
country: United States
facility: Research Site
state: Missouri
city: Bellevue
country: United States
facility: Research Site
state: Nebraska
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Haddon Heights
country: United States
facility: Research Site
state: New Jersey
city: Burlington
country: United States
facility: Research Site
state: North Carolina
city: Greensboro
country: United States
facility: Research Site
state: North Carolina
city: Mooresville
country: United States
facility: Research Site
state: North Carolina
city: Morehead City
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Vandalia
country: United States
facility: Research Site
state: Ohio
city: Medford
country: United States
facility: Research Site
state: Oregon
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Charleston
country: United States
facility: Research Site
state: South Carolina
city: Greer
country: United States
facility: Research Site
state: South Carolina
city: Spartanburg
country: United States
facility: Research Site
state: South Carolina
city: Summerville
country: United States
facility: Research Site
state: South Carolina
city: Dakota Dunes
country: United States
facility: Research Site
state: South Dakota
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Pearland
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Tomball
country: United States
facility: Research Site
state: Texas
city: Clinton
country: United States
facility: Research Site
state: Utah
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Burke
country: United States
facility: Research Site
state: Virginia
city: Manassas
country: United States
facility: Research Site
state: Virginia
city: Richmond
country: United States
facility: Research Site
state: Virginia
city: Baja
country: Hungary
facility: Research Site
city: Balatonfüred
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budaörs
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Eger
country: Hungary
facility: Research Site
city: Godollo
country: Hungary
facility: Research Site
city: Gyula
country: Hungary
facility: Research Site
city: Gödöllő
country: Hungary
facility: Research Site
city: Kecskemét
country: Hungary
facility: Research Site
city: Komárom
country: Hungary
facility: Research Site
city: Létavértes
country: Hungary
facility: Research Site
city: Nyíregyháza
country: Hungary
facility: Research Site
city: Pécs
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
facility: Research Site
city: Szekszárd
country: Hungary
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Oświęcim
country: Poland
facility: Research Site
city: Parczew
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Torun
country: Poland
facility: Research Site
city: Zgierz
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Baia Mare
country: Romania
facility: Research Site
city: Bucuresti
country: Romania
facility: Research Site
city: Bucuresti
country: Romania
facility: Research Site
city: Bucuresti
country: Romania
facility: Research Site
city: Galati
country: Romania
facility: Research Site
city: Oradea
country: Romania
facility: Research Site
city: Oradea
country: Romania
facility: Research Site
city: Oradea
country: Romania
facility: Research Site
city: Ploiesti
country: Romania
facility: Research Site
city: Timișoara
country: Romania
facility: Research Site
city: Banska Bystrica
country: Slovakia
facility: Research Site
city: Bardejov
country: Slovakia
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Dolny Kubin
country: Slovakia
facility: Research Site
city: Kosice
country: Slovakia
facility: Research Site
city: Levice
country: Slovakia
facility: Research Site
city: Levice
country: Slovakia
facility: Research Site
city: Lucenec
country: Slovakia
facility: Research Site
city: Nitra
country: Slovakia
facility: Research Site
city: Pezinok
country: Slovakia
facility: Research Site
city: Sturovo
country: Slovakia
facility: Research Site
city: Trebišov
country: Slovakia
facility: Research Site
city: Bloemfontein
country: South Africa
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Kempton Park
country: South Africa
facility: Research Site
city: Middelburg
country: South Africa
facility: Research Site
city: Parow
country: South Africa
facility: Research Site
city: Port Elizabeth
country: South Africa
facility: Research Site
city: Pretoria
country: South Africa
facility: Research Site
Study officials:
References:
citation: Jabbour SA, Frias JP, Ahmed A, Hardy E, Choi J, Sjostrom CD, Guja C. Efficacy and Safety Over 2 Years of Exenatide Plus Dapagliflozin in the DURATION-8 Study: A Multicenter, Double-Blind, Phase 3, Randomized Controlled Trial. Diabetes Care. 2020 Oct;43(10):2528-2536. doi: 10.2337/dc19-1350. Epub 2020 Aug 18.
citation: Guja C, Frias JP, Suchower L, Hardy E, Marr G, Sjostrom CD, Jabbour SA. Safety and Efficacy of Exenatide Once Weekly in Participants with Type 2 Diabetes and Stage 2/3 Chronic Kidney Disease. Diabetes Ther. 2020 Jul;11(7):1467-1480. doi: 10.1007/s13300-020-00815-z. Epub 2020 Apr 18.
citation: Jabbour SA, Frias JP, Hardy E, Ahmed A, Wang H, Ohman P, Guja C. Safety and Efficacy of Exenatide Once Weekly Plus Dapagliflozin Once Daily Versus Exenatide or Dapagliflozin Alone in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Monotherapy: 52-Week Results of the DURATION-8 Randomized Controlled Trial. Diabetes Care. 2018 Oct;41(10):2136-2146. doi: 10.2337/dc18-0680. Epub 2018 Aug 6.
citation: Frias JP, Guja C, Hardy E, Ahmed A, Dong F, Ohman P, Jabbour SA. Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8): a 28 week, multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes Endocrinol. 2016 Dec;4(12):1004-1016. doi: 10.1016/S2213-8587(16)30267-4. Epub 2016 Sep 16.