A Multicenter, Double-Blind, Placebo-Controlled, Parallel Group, Randomized, Phase 2Trial to Evaluate the Glycemic Efficacy, Renal Safety, Pharmacokinetics, andPharmacodynamics of Dapagliflozin in Subjects with Type 2 Diabetes Mellitus andModerate Renal Impairment Who Have Inadequate Glycemic Control.Revised Protocol 01, incorporating Protocol Amendment 02 (Version 1.0, Date 10-Apr-2008). And Pharmacogenetics Blood Sample Amendment 01 - Site specific (Version 2.0, Date 10-Mar-2008).

Phase 1

• Conditions: DIABETES,NOS; MedDRA version: 9.1Level: LLTClassification code 10045242Term: Type II diabetes mellitus

• Registration Number: EUCTR2008-001921-33-FR
• Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2008-07-30
• Study Completion: 2011-06-01
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 504

Inclusion Criteria

1) Subjects must be willing and able to give signed and dated written informed consent.
2) Subjects must have type 2 diabetes with inadequate glycemic control, defined as
central laboratory A1C = 7.0% and = 11.0%.
Note: A one-time central laboratory re-test of the A1C is allowed in subjects with an
initial central enrollment A1C of 6.9% as determined by the Investigator. In situations
where the central laboratory A1C value meets criteria for re-test, such a re-test of the A1C value is allowed provided the subject is otherwise fully eligible, as determined by the Investigator.
3) Subjects on a stable anti-diabetic regimen. A stable anti-diabetic regimen is defined as either diet and exercise therapy alone or in combination with a regimen of any approved anti-diabetic medication(s), including insulin, in which either the doses of oral anti-diabetic medications, exenatide, or pramlintide have not changed during the 6 weeks prior to enrollment; or the doses of long-acting insulin or intermediate-acting insulin have not varied by more than 20% during the 6 weeks prior to enrollment.
4) Subjects with moderate renal impairment. The degree of renal impairment is defined by the estimated GFR, according to the re-expressed abbreviated (four-variable) MDRD Study equation (see Protocol Section 4.1). Moderate renal impairment is defined as an eGFR 30 mL/min/1.73m2 to 59 mL/min/1.73m2.
5) BMI = 45.0 kg/m2 at the enrollment visit.
6) Men and women, = 18 years of age at the time of the enrollment visit.
Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study in such a manner that the
risk of pregnancy is minimized.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1)WOCBP unwilling or unable to use acceptable method to avoid pregnancy for entire study period
2)Pregnant or breastfeeding Women
3)Women with a positive pregnancy test on enrollment or prior to investigational
product administration
4)Aspartate Aminotransferase >3X ULN
5)Alanine Aminotransferase >3X ULN
6)Total Bilirubin >2 mg/dL (34.2 µmol/L)
7)Serum Potassium >5.5 meq/L
8)Serum Phosphorus =6.5 mg/dL
Note: one-time retest may be allowed, as determined by the Investigator, after a
minimum of 2 weeks following the initiation or adjustment of phosphate binder
medication. Such cases should be discussed with the Sponsor prior to re-testing the
serum phosphorus
9)Serum Calcium <8 mg/dL or >ULN
10)Positive for hepatitis B surface antigen
11)Positive for anti-hepatitis C virus antibody
12)Hemoglobin =9.0 g/dL (90 g/L) for men; hemoglobin =8.0 g/dL (80 g/L) for women
13)Creatine Kinase >3X ULN
14)Abnormal free T4 values. Abnormal TSH value at enrollment will be further evaluated by free T4. Subjects with abnormal free T4 values will be excluded
15)History of diabetes insipidus
16)Symptoms of poorly controlled diabetes that would preclude participation in this trial including but not limited to marked polyuria & polydipsia with greater than 10%
weight loss during the 3 months prior to enrollment, or other signs & symptoms
17)History of diabetic ketoacidosis or hyperosmolar nonketotic coma
18)Severe uncontrolled hypertension defined as systolic blood pressure
=180 mmHg &/or diastolic blood pressure = 110 mmHg
19)Myocardial infarction
20)Cardiac surgery or revascularization
21)Unstable angina
22)Unstable congestive heart failure
23)CHF New York Heart Association Class III or IV (See Protocol Appendix 3)
24)Transient ischemic attack or significant cerebrovascular disease
25)Unstable or previously undiagnosed arrhythmia
26)History of rapidly progressing renal disease
27)History of lupus nephritis
28)History of renal or systemic vasculitis
29)History of familial renal glucosuria
30)History of renal artery stenosis, with renovascular hypertension or ischemic
nephropathy
31)History of renal transplant
32)Hemodialysis, ultrafiltration therapy, or peritoneal dialysis within 6 months prior to enrollment
33)Significant hepatic disease, including, but not limited to, chronic active hepatitis
1/or severe hepatic insufficiency
34)Documented history of hepatotoxicity with any medication
35)Documented history of severe hepatobiliary disease
36)History of hemoglobinopathy with the exception of sickle cell trait or
thalassemia minor; or chronic or recurrent hemolysis
37)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
6 weeks prior to enrollment visit
38)Malignancy within 5 years of enrollment visit (with exception of treated basal cell or treated squamous cell carcinoma)
39)Known immunocompromised status, including but not limited to, individuals who
have undergone organ transplantation or who are positive for HIV
40)Allergies or contraindication to the contents of dapagliflozin tablets
41)Administration of metformin within 6 weeks of enrollment
42)Replacement or chronic systemic corticosteroid, defined as any dose of systemic
corticosteroid taken for >4 weeks within 3 months prior to enrollment visit
43)History of bariatric surgery or lap-band procedure
44)Administration of sibutramine, phentermine, orlistat, rimonabant, benzphetamine,
diethylpropion,

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified