Safety and Efficacy of Dapagliflozin in Triple Therapy to Treat Subjects With Type 2 Diabetes

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT01646320
• Date of registration: 18/07/2012
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: Safety and Efficacy of Dapagliflozin in Triple Therapy to Treat Subjects With Type 2 Diabetes
• Scientific title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Therapy With Dapagliflozin Added to Saxagliptin in Combination With Metformin Compared to Therapy With Placebo Added to Saxagliptin in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin and Saxagliptin
• Date of first enrolment: September 2012
• Target sample size: 320
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01646320
• Study type: Interventional
• Phase: Phase 3

Countries of recruitment

Czech Republic, India, Mexico, Poland, Puerto Rico, Romania, Russian Federation, Turkey, United Kingdom, United States

Contacts

• Name: Bristol-Myers Squibb
• Affiliation: Bristol-Myers Squibb

Key inclusion & exclusion criteria

Inclusion Criteria

1. Signed Written Informed Consent

1. Subjects must be willing and able to give signed and dated written informed
consent.

2. Target Population

For inclusion into Stratum A:

i) Subjects with T2DM with inadequate glycemic control, defined as central laboratory
HbA1c = 8.0 and = 11.5% obtained at the screening visit (ie Week -18 visit), on stable
metformin therapy alone for at least 8 weeks prior to screening visit at a dose = 1500
mg per day

For inclusion into Stratum B:

ii) Subjects with T2DM with inadequate glycemic control, and HbA1c = 7.5 and = 10.5%
obtained at the screening visit and on stable metformin therapy at a dose = 1500 mg
per day AND a DPP4 inhibitor at the maximum approved dose for at least 8 weeks prior
to screening visit.

b) C-peptide = 1.0 ng/mL (0.34 nmol/L) at screening visit. c) BMI = 45.0 kg/m2 at the
screening visit.

3. Age and Reproductive Status

1. Men and women, aged = 18 years old at time of screening visit.

2. Women of childbearing potential (WOCBP) must be using an acceptable method of
contraception to avoid pregnancy throughout the study in such a manner that the
risk of pregnancy is minimized.

3. WOCBP must have a negative serum or urine pregnancy test within 24 hours prior to
the start of investigational product.

4. Women must not be breastfeeding

5. Sexually active fertile men must use highly effective birth control if their
partners are WOCBP.

Exclusion Criteria

1. Target Disease Exceptions

1. History of diabetes insipidus

2. 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 three months prior to screening, or other signs
and symptoms.

3. History of diabetic ketoacidosis or hyperosmolar nonketotic coma.

2. Medical History and Concurrent Diseases

1. History of bariatric surgery or lap-band procedure within 12 months prior to
screening.

2. Any unstable endocrine, psychiatric or rheumatic disorders as judged by the
Investigator.

3. Subject who, in the judgment of the investigator, may be at risk for dehydration
or volume depletion that may affect the interpretation of efficacy or safety data
and concomitant use of loop diuretics in countries where this is not recognized
in the Dapagliflozin label.

4. Subject is currently abusing alcohol or other drugs or has done so within the
last 6 months.

Acute Vascular Event:

5. Uncontrolled hypertension defined as systolic blood pressure (SBP) = 160 mmHg
and/or diastolic blood pressure (DBP) = 100 mmHg.

6. Cardiovascular Disease within 3 months of the screening visit [ie myocardial
infarction, cardiac surgery or revascularization (CABG/PTCA), unstable angina,
stroke or transient ischemic attack (TIA)].

7. Congestive heart failure as New York Association (NYHA) class IV, unstable or
acute congestive heart failure.

Renal Diseases:

8. Moderate or severe impairment of renal function [defined as eGFR < 60
mL/min/1.73m2 (estimated by MDRD) or serum creatinine (Scr) = 1.5 mg/dL in males
or = 1.4 mg/dL in females.]

9. Conditions of congenital renal glucosuria

Hepatic Diseases:

10. Significant hepatic disease, including, but not limited to, chronic active
hepatitis and/or severe hepatic insufficiency, including subjects with ALT and/or
AST > 3x ULN and or Total Bilirubin > 2.5 x ULN.

Hematological and Oncological Disease/Conditions:

11. History of hemoglobinopathy, with the exception of sickle cell trait (SA) or
thalassemia minor; or chronic or recurrent hemolysis.

12. Malignancy within 5 years of the screening visit (with the exception of treated
basal cell or treated squamous cell carcinoma)

13. Known immunocompromised status, including but not limited to, individuals who
have undergone organ transplantation or who are positive for the human
immunodeficiency virus.

14. Donation of blood or blood products to a blood bank, blood transfusion, or
participation in a clinical study requiring withdrawal of > 400 mL of blood
during the 6 months prior to the screening visit.

Prohibited treatment and therapies:

15. Administration of any antihyperglycemic therapy, other than metformin and DPP4's,
for more than 14 days (consecutive or not) during the 12 weeks prior to
screening, as well as previous exposure to DPP4 or SGLT-2 inhibitor in any DPP4
or SGLT-2 inhibitor trial is an exclusion criterion.

16. Current treatment with potent cytochrome P450 3A4/5 inhibitors (in countries
where dose adjustment would be required by the dapagliflozin label).

17. Administration of any other investigational drug or participation in any
interventional clinical studies within 30 days of planned screening to this
study. Subjects who failed to satisfy all eligibility criteria at screening and
did not enter the lead-in or open-label period in CV181-168 or CV181-169 studies
specifically, do not need to wait 30 days.

3. Physical and Laboratory Test Findings

a) Hemoglobin = 11.0 g/dL (110 g/L) for men; hemoglobin = 10.0 g/dL (100 g/L) for
women

b) Presence of hematuria:

i) For male subjects being considered for Stratum A: microscopic hematuria present at
Week -18 or Week -16 AND no common cause that can be confirmed is exclusionary. Male
subjects with a confirmed common cause can be entered into the open-label phase with a
documented negative result for hematuria microscopic urinalysis performed by the
central laboratory.

ii) For male subjects being considered for Stratum B: microscopic hematuria present at
Week -10 or Week -8 AND no common cause that can be confirmed is exclusionary. Male
subjects with a confirmed common cause can be entered into the open-label phase with a
documented negative result for hematuria microscopic urinalysis performed by the
central laboratory.

NOTE: Female sub}ects with hematuria can be entered i


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Type 2 Diabetes

Intervention(s)

Drug: Placebo matching with Dapagliflozin

Drug: Saxagliptin

Drug: Dapagliflozin

Drug: Metformin immediate release (IR)

Primary Outcome(s)

Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 [Time Frame: From Baseline to Week 24]

Secondary Outcome(s)

Percentage of Subjects Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF]) [Time Frame: From baseline to week 24]

Adjusted Mean Change From Baseline in Body Weight at Week 24 [Time Frame: From baseline to Week 24]

Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 24 [Time Frame: From Baseline to Week 24]

Adjusted Mean Change From Baseline in 120-minute Postprandial Glucose (PPG) at Week 24 [Time Frame: From Baseline to Week 24]

Secondary ID(s)

MB102-129

2011-006324-20

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 11/04/2016
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01646320