A Multi-Center, Randomized, Double-Blind, Phase III Trial to Evaluate the Safety and Efficacy of Saxagliptin Co-administered With Dapagliflozin Compared to Saxagliptin or Dapagliflozin All Given as add-on Therapy to Metformin in Subject With Type 2 Diabetes

NCT02681094 | Completed Phase 3 Results

• 1 other identifier: D1683C00005
• Study Type: interventional
• Target: 905
• Locations: 6 countries
• Sites: 110

Brief Summary

The aim of this study is to evaluate safety and efficacy of therapy with saxagliptin 5mg co-administered with dapagliflozin 5mg, compared to therapy with saxagliptin 5mg or dapagliflozin 5mg in patients who are inadequately controlled on ≥1500mg/day of metformin monotherapy.

Conditions

Type 2 Diabetes Mellitus; Inadequate Glycaemic Control

Keywords

Diabetes Mellitus Type 2,; saxagliptin,; dapagliflozin,; metformin

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in HbA1c at Week 24

  To demonstrate the superiority of the change from baseline HbA1c achieved with the co-administered saxagliptin 5 mg and dapagliflozin 5 mg to either agent individually after 24 weeks. Results were presented for the modified full analysis set. Note: Baseline was defined as the last assessment on or prior to the date of the first dose of the study medication.

  Baseline and week 24

Secondary Outcomes (3)

• Proportion of Participants Achieving HbA1c <7.0% at 24 Weeks

  Baseline and week 24

• Change in Fasting Plasma Glucose at 24 Weeks

  Baseline and week 24

• Change in Total Body Weight at 24 Weeks

  Baseline and week 24

Study Arms (3)

Saxagliptin+Dapagliflozin+Metformin

ACTIVE COMPARATOR

5 mg Tablets, Oral, Once daily, 24 weeks for Saxagliptin and Dapagliflozin

Drug: Dapagliflozin; Drug: Saxagliptin

Dapagliflozin+Saxagliptin placebo+Metformin

ACTIVE COMPARATOR

5 mg Tablets, Oral, Once daily, 24 weeks for Dapagliflozin and Saxagliptin Placebo

Drug: Dapagliflozin; Drug: Placebo for Saxagliptin

Saxagliptin+Dapagliflozin placebo+metformin

ACTIVE COMPARATOR

5 mg Tablets, Oral, Once daily, 24 weeks for Saxagliptin and Dapagliflozin placebo

Drug: Placebo for Dapagliflozin; Drug: Saxagliptin

Interventions

Dapagliflozin DRUG

5mg, orally, Green, plain, diamond-shaped, film-coated tablet

Also known as: Forxiga

Dapagliflozin+Saxagliptin placebo+Metformin; Saxagliptin+Dapagliflozin+Metformin

Placebo for Dapagliflozin DRUG

Does not contain active ingredient, orally, Green, plain, diamond-shaped, film-coated tablet

Saxagliptin+Dapagliflozin placebo+metformin

Saxagliptin DRUG

5mg, orally, Plain, yellow, biconvex, round, film-coated tablet

Also known as: Onglyza™

Saxagliptin+Dapagliflozin placebo+metformin; Saxagliptin+Dapagliflozin+Metformin

Placebo for Saxagliptin DRUG

Does not contain active ingredient, orally, Plain, yellow, biconvex, round, film-coated tablet

Dapagliflozin+Saxagliptin placebo+Metformin

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged ≥18 years old at time of informed consent;
• Patients with Type 2 diabetes mellitus (T2DM) defined as HbA1C≥7.5% to ≤10.0% at screening visit;
• Stable metformin therapy for at least 8 weeks prior to enrolment at a dose of ≥1500mg per day;
• BMI ≤45.0kg/m2 at Enrolment visit;
• Fasting Plasma Glucose (FPG) ≤ 270mg/dl(15.0mmol/L) at the enrolment visit;
• For Females Only: Women of childbearing potential (WOCBP) must be using an acceptable method of contraception to avoid pregnancy throughout the study and for at least 4 weeks after the last dose of study medication in such a manner that the risk of pregnancy is minimized.

You may not qualify if:

• History of diabetes insipidus, Type 1 diabetes or Latent Autoimmune Diabetes of Adults, diabetic ketoacidosis or hyperosmolar nonketotic coma and Symptoms of poorly controlled diabetes that would preclude participation in this trial including but not limited to marked polyuria and polydipsia with greater than 10% weight loss during the 3 months prior to Enrolment (Visit 1), or other signs and symptoms.
• History of pancreatitis.
• Administration of any antihyperglycaemic therapy, other than metformin, for more than 14 days (consecutive or not) during the 8 weeks prior to enrolment
• Any use of DPP-4 inhibitor or SGLT-2 inhibitor within 8 weeks prior to enrolment.
• Significant hepatic disease, including, but not limited to, chronic active hepatitis and/or severe hepatic insufficiency and/or significant abnormal liver function, including patients with Alanine transaminase (ALT) and/or Aspartate transaminase (AST) ≥3x ULN (Upper Limit of Normal)and/or Total Bilirubin ≥2.0x ULN. History of severe hepatobiliary disease or hepatotoxicity with any medication. Positive serologic evidence of current infectious liver disease, including patients who are known to be positive for Hepatitis viral antibody ImmunoglobulinM (IgM), Hepatitis B surface antigen, and Hepatitis C virus antibody.
• Moderate or severe impairment of renal function \[defined as Estimated Glomerular Filtration Rate (eGFR) \<60milliLitre/min/1.73 m2 (estimated by Modification in Diet and Renal Disease (MDRD)) or serum creatinine ≥1.5mg/dL in males or ≥1.4mg/dL in females\]. Conditions of congenital renal glucosuria, history of unstable or rapidly progressing renal disease.
• History of any clinically significant disease or disorder which, in the opinion of the investigator, may put the patient at risk because of participation in the study, may influence the results, or may limit the patient's ability to participate in or complete the study.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (110)

Research Site

Saraland, Alabama, 36571, United States

Location

Research Site

Fresno, California, 93702, United States

Location

Research Site

Harbor City, California, 90710, United States

Location

Research Site

Hawaiian Gardens, California, 90716, United States

Location

Research Site

Lancaster, California, 93534, United States

Location

Research Site

Los Angeles, California, 90057, United States

Location

Research Site

Montclair, California, 91763, United States

Location

Research Site

Pomona, California, 91767, United States

Location

Research Site

Spring Valley, California, 91978, United States

Location

Research Site

Vallejo, California, 94592, United States

Location

Research Site

Denver, Colorado, 80220, United States

Location

Research Site

Northglenn, Colorado, 80234, United States

Location

Research Site

Wheat Ridge, Colorado, 80033, United States

Location

Research Site

Waterbury, Connecticut, 06708, United States

Location

Research Site

Cooper City, Florida, 33024, United States

Location

Research Site

Doral, Florida, 33166, United States

Location

Research Site

Hialeah, Florida, 33012, United States

Location

Research Site

Miami, Florida, 33176, United States

Location

Research Site

Miami, Florida, 33186, United States

Location

Research Site

Miami Lakes, Florida, 33016, United States

Location

Research Site

Buford, Georgia, 30518, United States

Location

Research Site

Chicago, Illinois, 60607, United States

Location

Research Site

Hazel Crest, Illinois, 60429, United States

Location

Research Site

New Orleans, Louisiana, 70115, United States

Location

Research Site

Zachary, Louisiana, 70791, United States

Location

Research Site

Biloxi, Mississippi, 39531, United States

Location

Research Site

Florissant, Missouri, 63031, United States

Location

Research Site

Albany, New York, 12203, United States

Location

Research Site

The Bronx, New York, 10459, United States

Location

Research Site

Asheville, North Carolina, 28801, United States

Location

Research Site

Mooresville, North Carolina, 28117, United States

Location

Research Site

Fargo, North Dakota, 58103, United States

Location

Research Site

Columbus, Ohio, 43201, United States

Location

Research Site

Maumee, Ohio, 43537, United States

Location

Research Site

East Providence, Rhode Island, 02914, United States

Location

Research Site

West Columbia, South Carolina, 29169, United States

Location

Research Site

Dallas, Texas, 75208, United States

Location

Research Site

Dallas, Texas, 75230, United States

Location

Research Site

El Paso, Texas, 79935, United States

Location

Research Site

Fort Worth, Texas, 76132, United States

Location

Research Site

Houston, Texas, 77004, United States

Location

Research Site

Houston, Texas, 77036, United States

Location

Research Site

Houston, Texas, 77040, United States

Location

Research Site

Odessa, Texas, 79761, United States

Location

Research Site

Sugar Land, Texas, 77479, United States

Location

Research Site

Waco, Texas, 76710, United States

Location

Research Site

Salt Lake City, Utah, 84102, United States

Location

Research Site

Norfolk, Virginia, 23510, United States

Location

Research Site

Moncton, New Brunswick, E1G 1A7, Canada

Location

Research Site

Bridgewater, Nova Scotia, B4V 3N2, Canada

Location

Research Site

Brampton, Ontario, L7A 3P1, Canada

Location

Research Site

Etobicoke, Ontario, M9W 4L6, Canada

Location

Research Site

Greater Sudbury, Ontario, P3E 6C3, Canada

Location

Research Site

London, Ontario, N5W 6A2, Canada

Location

Research Site

Scarborough Village, Ontario, M1P 2T7, Canada

Location

Research Site

Toronto, Ontario, M3J 2C5, Canada

Location

Research Site

Chicoutimi, Quebec, G7H 7K9, Canada

Location

Research Site

Lévis, Quebec, G6W 0M5, Canada

Location

Research Site

Mirabel, Quebec, J7J 2K8, Canada

Location

Research Site

Pointe-Claire, Quebec, H9R 3J1, Canada

Location

Research Site

Saint-Marc-des-Carrieres, Quebec, G0A 4B0, Canada

Location

Research Site

Chrudim III, 537 01, Czechia

Location

Research Site

České Budějovice, 370 01, Czechia

Location

Research Site

Jílové u Prahy, 254 01, Czechia

Location

Research Site

Ostrava, 710 00, Czechia

Location

Research Site

Pardubice, 530 02, Czechia

Location

Research Site

Pilsen, 301 66, Czechia

Location

Research Site

Prague, 100 00, Czechia

Location

Research Site

Prague, 140 46, Czechia

Location

Research Site

Prague, 149 00, Czechia

Location

Research Site

Prague, 181 00, Czechia

Location

Research Site

Praha Klanovice, 190 14, Czechia

Location

Research Site

Uherské Hradiště, 686 01, Czechia

Location

Research Site

Berlin, 10787, Germany

Location

Research Site

Bünde, 32257, Germany

Location

Research Site

Essen, 45359, Germany

Location

Research Site

Giengen an der Brenz, 89537, Germany

Location

Research Site

Großheirath, 96269, Germany

Location

Research Site

Hof, 95030, Germany

Location

Research Site

Hohenmölsen, 06679, Germany

Location

Research Site

Karlsruhe, 76199, Germany

Location

Research Site

Lichtenfels, 96215, Germany

Location

Research Site

Meine, 38527, Germany

Location

Research Site

Münster, 48153, Germany

Location

Research Site

Rehburg-Loccum, 31547, Germany

Location

Research Site

Stolberg, 52222, Germany

Location

Research Site

Villingen-Schwenningen, 78048, Germany

Location

Research Site

Guadalajara, 44160, Mexico

Location

Research Site

Guadalajara, 44600, Mexico

Location

Research Site

Guadalajara, 44670, Mexico

Location

Research Site

México, 03800, Mexico

Location

Research Site

Monterrey, 64460, Mexico

Location

Research Site

Monterrey, 64465, Mexico

Location

Research Site

Zapopan, 45116, Mexico

Location

Research Site

Arkhangelsk, 163001, Russia

Location

Research Site

Izhevsk, 426063, Russia

Location

Research Site

Kazan', 420008, Russia

Location

Research Site

Moscow, 119991, Russia

Location

Research Site

Moscow, 127473, Russia

Location

Research Site

Perm, 614056, Russia

Location

Research Site

Perm, 6144090, Russia

Location

Research Site

Rostov-on-Don, 344022, Russia

Location

Research Site

Saint Petersburg, 196143, Russia

Location

Research Site

Saint Petersburg, 196601, Russia

Location

Research Site

Saint Petersburg, 198013, Russia

Location

Research Site

Tver', 170036, Russia

Location

Research Site

Ufa, 450071, Russia

Location

Research Site

Vladikavkaz, 362007, Russia

Location

Research Site

Yekaterinburg, 620039, Russia

Location

Research Site

Yekaterinburg, 620219, Russia

Location

Related Links

• d1683c00005 csp Redacted
• D1683C00005 SAP redacted

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

dapagliflozin; saxagliptin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Global Clinical Leader
• Organization: AstraZeneca

clinicaltrialtransparency@astrazeneca.com

+46 766 346712

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2016
• First Posted: February 12, 2016
• Study Start: February 26, 2016
• Primary Completion: July 15, 2017
• Study Completion: July 15, 2017
• Last Updated: October 10, 2018
• Results First Posted: October 10, 2018

Record last verified: 2018-09

Locations

DE (14); RU (16); ME (7); US (48); CA (13); CZ (12)