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

AstraZeneca

Status and phase: Completed; Phase 3

Conditions: Inadequate Glycaemic Control; Type 2 Diabetes Mellitus

Treatments: Drug: Dapagliflozin; Drug: Saxagliptin; Drug: Placebo for Saxagliptin; Drug: Placebo for Dapagliflozin

Study type: Interventional

Funder types: Industry

Identifiers

NCT02681094

D1683C00005

Details and patient eligibility

About

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.

Enrollment: 905 patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients aged ≥18 years old at time of informed consent;
2. Patients with Type 2 diabetes mellitus (T2DM) defined as HbA1C≥7.5% to ≤10.0% at screening visit;
3. Stable metformin therapy for at least 8 weeks prior to enrolment at a dose of ≥1500mg per day;
4. BMI ≤45.0kg/m2 at Enrolment visit;
5. Fasting Plasma Glucose (FPG) ≤ 270mg/dl(15.0mmol/L) at the enrolment visit;
6. 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.

Exclusion criteria

1. 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.
2. History of pancreatitis.
3. Administration of any antihyperglycaemic therapy, other than metformin, for more than 14 days (consecutive or not) during the 8 weeks prior to enrolment
4. Any use of DPP-4 inhibitor or SGLT-2 inhibitor within 8 weeks prior to enrolment.
5. 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.
6. 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.
7. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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905 participants in 3 patient groups

Saxagliptin+Dapagliflozin+Metformin

Active Comparator group

Description:

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

Treatment:

Drug: Saxagliptin

Drug: Dapagliflozin

Dapagliflozin+Saxagliptin placebo+Metformin

Active Comparator group

Description:

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

Treatment:

Drug: Placebo for Saxagliptin

Drug: Dapagliflozin

Saxagliptin+Dapagliflozin placebo+metformin

Active Comparator group

Description:

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

Treatment:

Drug: Placebo for Dapagliflozin

Drug: Saxagliptin