ESR-15-11293 - Saxa/Dapa, Safety and Efficacy Study

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02613897
• Date of registration: 12/11/2015
• Prospective Registration: Yes
• Primary sponsor: The University of Texas Health Science Center at San Antonio
• Public title: ESR-15-11293 - Saxa/Dapa, Safety and Efficacy Study
• Scientific title: A 16-wk, Uni-center, Randomized, Double-blind, Parallel, Phase 3b Trial to Evaluate Efficacy of Saxagliptin + Dapagliflozin vs.Dapagliflozin With Regard to EGP in T2DM With Insufficient Glycemic Control on Metformin+/-Sulfonylurea Therapy
• Date of first enrolment: January 2016
• Target sample size: 56
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02613897
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: N/A

Countries of recruitment

United States

Contacts

• Name: Eugenio Cersosimo, MD
• Affiliation: The University of Texas Health Science Center at San Antonio

• Name: Ralph A DeFronzo, MD
• Affiliation: The University of Texas Health Science Center at San Antonio

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Provision of informed consent prior to any study-specific procedures.

2. Is able to read, understand, and sign the Informed Consent Forms (ICFs) and, if
applicable, an Authorization to Use and Disclose Protected Health Information form
(consistent with Health Insurance Portability and Accountability Act of 1996
legislation), communicate with the Investigator, and understand and comply with
protocol requirements, including the use of diary and glucose meter measurements.

3. Age = 18-70 years.

4. Has a diagnosis of T2DM.

5. Has HbA1c =7.5% and =11.0% obtained at Screening.

6. Treated with a stable dose of metformin =1000 mg/day or stable dose of metformin (=
1000 mg/day) plus sulfonylurea (glipizide, = 5 mg/day; glyburide, = 5 mg/day;
glimepiride, = 4 mg/day) for at least 8 weeks prior to Screening.

7. Has a BMI of 20 to 45 kg/m2 (inclusive) at Screening.

8. Is male, or is female, and meets all the following criteria:

- Not pregnant or breastfeeding.

- Negative pregnancy test result at Visit 1 (Screening).

- Women of childbearing potential (WOCBP; [including perimenopausal women who have
had a menstrual period within 1 year]) must practice and be willing to continue
to practice appropriate birth control (defined as a method that results in a low
failure rate, i.e., less than 1% per year, when used consistently and correctly,
such as implants, injectables, hormonal contraceptives [pills, vaginal rings, or
patches], some intrauterine contraceptive devices [levonorgestrel-releasing or
copper-T], tubal ligation or occlusion, or a vasectomized partner) during the
entire duration of the study. As applicable, all methods must be in effect prior
to receiving the first dose of study medication.

Exclusion Criteria:

Target Disease Exceptions

1. Clinically diagnosed with Type I diabetes .

2. History of diabetic ketoacidosis, hyperosmolar nonketotic coma, or corticosteroid
induced Type 2 diabetes.

Medical History and Concurrent Diseases

3. History of bariatric surgery or lap-band surgery, or either procedure is planned
during the time period of the study.

4. History of any unstable endocrine, psychiatric, rapidly progressing, or unstable renal
disease, or rheumatic disorder, as judged by the Investigator.

5. Patients who, in the judgment of the Investigator, may be at risk for dehydration or
volume depletion that may affect the patient's safety and/or the interpretation of
efficacy or safety data.

6. Has evidence of current abuse of drugs or alcohol or a history of abuse within the
past 52 weeks that, in the Investigator's opinion, would cause the individual to be
noncompliant.

Cardiovascular Conditions

7. Cardiovascular disease within 3 months of Screening (i.e., MI, cardiac surgery,
revascularization, unstable angina, stroke, transient ischemic attack, or arrhythmia).

8. Presence or history of severe congestive heart failure (New York Heart Association
Class III and IV [CCNYHA 1994]), unstable or acute congestive heart failure, and/or
known left ventricular ejection fraction of =40%.

Note: Eligible patients with congestive heart failure, especially those who are on
diuretic therapy, should have careful monitoring of their volume status throughout the
study.

Kidney Conditions

9. Estimated (eGFR) <60±5 mL/min/1.73 m2 or a measured serum creatinine of >1.4 mg/dL for
female patients and >1.5 mg/dL for male patients. If the serum creatinine is = 1.4
(female) or = 1.5 (male) and the eGFR is = 60±5 ml/min/1.73m2, the subject is eligible
to participate in the study.

10. Congenital renal glucosuria. Hepatic Conditions

11. Significant hepatic disease, including, but not limited to, severe hepatic
insufficiency and/or significant abnormal liver function defined as aspartate
aminotransferase (AST) and/or alanine aminotransferase (ALT) of >3x upper limit of
normal (ULN).

12. Serum total bilirubin (TB) >2 mg/dL.

13. History of, or currently have, acute or chronic pancreatitis or have triglyceride
concentrations =500 mg/dL at Visit 1 (Screening).

14. Suspicion that the patient is infected with an infectious substance according to World
Health Organization risk categories A and B (see Appendix C).

15. Known severe hepatic disease, including chronic active hepatitis.

16. Positive serologic evidence of current infectious liver disease, including patients
positive for hepatitis B viral antibody IgM, hepatitis B surface antigen, and
hepatitis C virus antibody.

Hematological/Oncological Conditions

17. Malignancy within 5 years of Visit 1 (Screening), with the exception of treated in
situ basal cell or squamous cell carcinoma of the skin.

18. Hematocrit of <34% for both males and females. Prohibited Medications

19. Administration of any antihyperglycemic therapy, other than metformin or
metformin/sulfonylurea, for more than 14 days (consecutive or not) during the 12 weeks
prior to Visit 1 (Screening) and during the study unless per protocol for rescue.

20. Current treatment with potent cytochrome P450 3A4/5 inhibitors (e.g., atazanavir,
clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir,
saquinavir, and telithromycin).

21. Administration of any other investigational drug or participation in any
interventional clinical studies 30 days prior to Visit 1 (Screening).

22. Treatment with systemic corticosteroids for the last 3 months prior to Visit 1
(Screening).

23. Prescription or over-the-counter weight loss medications within 3 months prior to
Visit 1 (Screening).

Other

24. Patients with abnormal thyroid stimulating hormone (TSH) or free thyroxine (T4) values
at Visit 1 (Screening) will be excluded.

25. Has a clinically significant medical condition that could potentially affect study
participation and/or personal well-being, as judged by the Investigator.

26. Has clinically significant abnormal laboratory test values (clinical chemistry,
hematology, and urinalysis) as judged by the Investigator at Visit 1 (Screening).

27. Has known contraindications, allergies, or hypersensitivities to any study medication
or excipient as outlined in the IBs or local package inserts for saxagliptin and
dapagliflozin.

28. Has a contraindication to metformin use, including known metabolic or lactic


Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Diabetes Mellitus, Type 2

Intervention(s)

Drug: Placebo

Drug: Saxagliptin

Drug: Dapagliflozin

Primary Outcome(s)

Change in Endogenous Glucose Production (EGP) [Time Frame: Baseline and 16 weeks]

Secondary Outcome(s)

Change in Fasting Plasma Glucagon (FPG) [Time Frame: Change from baseline to 16 weeks]

Change in Lipid Oxidation [Time Frame: Change from baseline to 16 weeks]

Mean Oral Glucose Tolerance Test (OGTT) [Time Frame: Change from baseline to 16 weeks]

Change in BMI [Time Frame: Change from baseline to 16 weeks]

Change in Glucose Oxidation [Time Frame: Change from baseline to 16 weeks]

Change in Body Weight [Time Frame: Baseline to 16 weeks]

HBA1c [Time Frame: Change from baseline to 16 weeks]

Change in Free Fatty Acids (FFA) [Time Frame: Change from baseline to 16 weeks]

Secondary ID(s)

HSC20150742H

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

AstraZeneca

Results

• Results available: Yes
• Date Posted: 14/08/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02613897