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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT01619059
• Date of registration: 12/06/2012
• Prospective Registration: No
• Primary sponsor: AstraZeneca
• Public title: Safety and Efficacy of Saxagliptin 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 Triple Therapy With Saxagliptin Added to Dapagliflozin in Combination With Metformin Compared to Therapy With Placebo Added to Dapagliflozin in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin and Dapagliflozin
• Date of first enrolment: June 2012
• Target sample size: 315
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01619059
• Study type: Interventional
• Phase: Phase 3

Countries of recruitment

Canada, Czech Republic, Hungary, Mexico, Poland, Puerto Rico, Romania, Russian Federation, United States

Contacts

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

Key inclusion & exclusion criteria

Inclusion Criteria

1. Signed Written Informed Consent

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

2. Target Population

1. 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)

2. Stable metformin therapy for at least 8 weeks prior to screening visit at a dose
= 1500 mg per day.

3. C-peptide = 1.0 ng/mL (0.34 nmol/L) at screening visit.

4. 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. See Section 3.3.3 for the definition of WOCBP.

3. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25
IU/L or equivalent units of HCG) within 24 hours prior to the start of
investigational product.

4. Women must not be breastfeeding

5. Sexually active fertile men must use 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 recommended
as per 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.

Note: Subjects with SBP = 160mmHg and < 180mmHg or a DBP = 100 mmHg and < 110mmHg
will be able to enter the lead-in period, provided their hypertension treatment
is adjusted as deemed appropriate by the investigator. These subjects cannot be
randomized if their blood pressure remains with SBP = 160 mmHg or DBP = 100 mmHg
measured at Day 1.

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 (see Appendix
1), unstable or acute congestive heart failure. Note: eligible patients with
congestive heart failure, especially those who are on diuretic therapy, should
have careful monitoring of their volumes status throughout the study.

Renal Diseases:

8. Moderate or severe impairment of renal function [defined as eGFR < 60 mL/min/1.73
m2 (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, for more
than 14 days (consecutive or not) during the 12 weeks prior to screening, as well
as previous participation in any DPP-4 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 saxagliptin 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 CV181-169 or MB102-129 studies
specifically, do not need to wait 30 days.

3. Physical and Laboratory Test Findings

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

2. Male subjects with microscopic hematuria present at Week -18 or Week -16 AND no
common cause that can be confirmed. 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 subjects with hematuria can be entered into the open-label phase and
be randomized, but should be investigated according to local standards and best
clinical


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

Health Condition(s) or Problem(s) studied

Type 2 Diabetes

Intervention(s)

Drug: Saxagliptin

Drug: Placebo matching with Saxagliptin

Drug: Metformin IR

Drug: Dapagliflozin

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 Participants 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 2-hour Post Prandial Glucose (PPG) From a Liquid Meal Tolerance Test (MTT) 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]

Secondary ID(s)

2011-006323-37

CV181-168

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 17/03/2016
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01619059