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

NCT ID: NCT02229396

Last Updated: 2018-12-31

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

695 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-09-04

Study Completion Date

2017-12-28

Brief Summary

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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.

Detailed Description

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Conditions

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Diabetes Mellitus

Keywords

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Diabetes Mellitus Exenatide Dapagliflozin Diabetes medication Treatment efficacy Placebo Metabolism Cardiovascular metabolic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Exenatide Once Weekly 2 mg and Dapagliflozin Once Daily 10 mg

Group Type EXPERIMENTAL

Exantide with Dapagliflozin

Intervention Type DRUG

2 mg weekly suspension injection and 10 mg Dapagliflozin

Exenatide Once Weekly 2 mg Alone

Group Type EXPERIMENTAL

Exentide

Intervention Type DRUG

2 mg

Dapagliflozin Once Daily 10 mg Alone

Group Type ACTIVE_COMPARATOR

Dapagliflozin

Intervention Type DRUG

10 mg once daily Dapagliflozin

Interventions

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Exantide with Dapagliflozin

2 mg weekly suspension injection and 10 mg Dapagliflozin

Intervention Type DRUG

Exentide

2 mg

Intervention Type DRUG

Dapagliflozin

10 mg once daily Dapagliflozin

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Birmingham, Alabama, United States

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Huntsville, Alabama, United States

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Tuscumbia, Alabama, United States

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Glendale, Arizona, United States

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Tempe, Arizona, United States

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Anaheim, California, United States

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Chula Vista, California, United States

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El Cajon, California, United States

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Fresno, California, United States

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La Mesa, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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Mission Hills, California, United States

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Montclair, California, United States

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Oceanside, California, United States

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San Diego, California, United States

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San Diego, California, United States

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Tustin, California, United States

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Van Nuys, California, United States

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Boynton Beach, Florida, United States

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Clearwater, Florida, United States

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Coral Gables, Florida, United States

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Fort Lauderdale, Florida, United States

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Hialeah, Florida, United States

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Jacksonville, Florida, United States

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Jacksonville, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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North Miami Beach, Florida, United States

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Orlando, Florida, United States

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Orlando, Florida, United States

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Tampa, Florida, United States

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Williston, Florida, United States

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Chicago, Illinois, United States

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Avon, Indiana, United States

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Evansville, Indiana, United States

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Franklin, Indiana, United States

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Muncie, Indiana, United States

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Newton, Kansas, United States

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Monroe, Louisiana, United States

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Hazelwood, Missouri, United States

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Bellevue, Nebraska, United States

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Las Vegas, Nevada, United States

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Haddon Heights, New Jersey, United States

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Burlington, North Carolina, United States

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Greensboro, North Carolina, United States

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Mooresville, North Carolina, United States

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Morehead City, North Carolina, United States

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Cincinnati, Ohio, United States

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Vandalia, Ohio, United States

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Medford, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Charleston, South Carolina, United States

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Greer, South Carolina, United States

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Spartanburg, South Carolina, United States

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Summerville, South Carolina, United States

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Dakota Dunes, South Dakota, United States

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Memphis, Tennessee, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Pearland, Texas, United States

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San Antonio, Texas, United States

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Tomball, Texas, United States

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Clinton, Utah, United States

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Salt Lake City, Utah, United States

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Burke, Virginia, United States

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Manassas, Virginia, United States

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Richmond, Virginia, United States

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Baja, , Hungary

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Balatonfüred, , Hungary

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Budaörs, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Debrecen, , Hungary

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Eger, , Hungary

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Gödöllő, , Hungary

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Gyula, , Hungary

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Kecskemét, , Hungary

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Komárom, , Hungary

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Létavértes, , Hungary

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Nyíregyháza, , Hungary

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Pécs, , Hungary

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Szeged, , Hungary

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Szekszárd, , Hungary

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Lodz, , Poland

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Lodz, , Poland

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Lublin, , Poland

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Oświęcim, , Poland

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Parczew, , Poland

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Poznan, , Poland

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Torun, , Poland

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Zgierz, , Poland

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Baia Mare, , Romania

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Bucharest, , Romania

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Bucharest, , Romania

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Bucharest, , Romania

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Galati, , Romania

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Oradea, , Romania

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Oradea, , Romania

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Oradea, , Romania

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Ploieşti, , Romania

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Timișoara, , Romania

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Banská Bystrica, , Slovakia

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Bardejov, , Slovakia

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Bratislava, , Slovakia

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Bratislava, , Slovakia

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Bratislava, , Slovakia

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Dolný Kubín, , Slovakia

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Košice, , Slovakia

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Levice, , Slovakia

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Levice, , Slovakia

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Lučenec, , Slovakia

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Nitra, , Slovakia

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Pezinok, , Slovakia

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Štúrovo, , Slovakia

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Trebišov, , Slovakia

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Bloemfontein, , South Africa

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Cape Town, , South Africa

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Johannesburg, , South Africa

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Kempton Park, , South Africa

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Middelburg, , South Africa

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Parow, , South Africa

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Port Elizabeth, , South Africa

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Pretoria, , South Africa

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Countries

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United States Hungary Poland Romania Slovakia South Africa

References

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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.

Reference Type DERIVED
PMID: 32816874 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32306296 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30082326 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27651331 (View on PubMed)

Related Links

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Other Identifiers

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2014-003503-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D5553C00003

Identifier Type: -

Identifier Source: org_study_id