A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 3 Trial to Evaluate the Efficacy and Safety of 2.5 mg Saxagliptin, PO, BID, in Combination with Metformin in Subjects with Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin, Alone.
- Conditions
- Type 2 Diabetes MellitusMedDRA version: 9.1Level: LLTClassification code 10063624Term: Type II diabetes mellitus inadequate control
- Registration Number
- EUCTR2009-010224-25-HU
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 152
Signed Written Informed Consent
1) Subjects must be willing and able to give written informed consent.
2) Subjects with a diagnosis of type 2 diabetes mellitus.
3) Subjects must be on a stable, BID dosing of at least 1500 mg of metformin IR for = 8 weeks prior to enrollment.
4) Subjects must have a A1C = 7.0% and = 10.0% at screening to be randomized.
5) Subjects must have a fasting C-peptide = 0.8 ng/mL (0.34 nmol/L) at screening.
6) Subjects must have a body mass index = 45.0 kg/m2.
7) Men and women, ages 18 to 78 (inclusive).
WOCBP must be using an adequate method of contraception to avoid pregnancy
throughout the study, and up to 4 weeks after last study drug was taken in such a
manner that the risk of pregnancy is minimized.
WOCBP include any female who has experienced menarche and who has not
undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or
bilateral oophorectomy) or is not postmenopausal. Post menopause is defined as:
• Amenorrhea = 12 consecutive months without another cause or,
• For women with irregular menstrual periods and on hormone replacement therapy
(HRT), a documented serum follicle stimulating hormone (FSH) level
= 35 mIU/mL.
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
1) WOCBP who are unwilling or unable to use an
acceptable method to avoid pregnancy for the entire study period and up to 4 weeks
after the final dose of study drug.
2) Women who are pregnant or breastfeeding.
3) Women with a positive urine HCG pregnancy test at randomization or prior to
investigational product administration.
4) Sexually active fertile men not using effective birth control for the entire study period and up to 4 weeks after last study drug was taken if their partners are WOCBP.
5) Symptoms of poorly controlled T2DM including, but not limited to marked polyuria
and polydipsia, with a greater than 10% weight loss during the 3 months prior to
screening or other signs and symptoms
6) History of diabetic ketoacidosis or hyperosmolar nonketotic coma.
7) Insulin therapy within 1 year of screening (with the exception of insulin therapy
during a hospitalization or use in pregnant women with gestational diabetes).
8) Significant cardiovascular history defined as:
a) History of myocardial infarction, coronary artery or bypass graft(s), valvular
disease or repair, unstable angina pectoris, transient ischemic attack, or cerebral
vascular event within 3 months prior to entry into the study or,
b) Congestive heart failure defined as New York Heart Association (NYHA) stage
III or IV and / or known left ventricular ejection fraction = 40%
9) History of hemoglobinopathies
10) Chronic or repeated intermittent corticosteroid treatment.
11) History of unstable or rapidly progressive renal disease.
12) History of alcohol or drug abuse within 1 year prior to enrollment.
13) Unstable psychiatric disorders.
14) Administration of any other study drug or participation in a clinical research trial
within 30 days of planned enrollment to this study (or a longer period if dictated by
local regulatory authorities).
15) Any condition, which in the Investigator’s opinion, may render the subject unable to complete the study or may pose significant risk to the subject.
16) Subjects on a commercial weight loss program with ongoing weight loss, or on an
intensive exercise program.
17) FPG > 270 mg/dL prior to randomization.
18) Active liver disease and/or significant abnormal liver function (defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 x ULN and/or serum total bilirubin > 2.0 mg/dL).
19) History of positive serologic evidence of current infectious liver disease including
anti-HAV (IgM), HbsAg, or anti-HCV. Subjects who may have isolated positive anti
HBs may be included.
20) Serum creatinine (Scr) = 1.50 mg/dL (133 µmol/L) for male subjects and
= 1.40 mg/dL (124 µmol/L) for female subjects.
21) Anemia of any etiology defined as hemoglobin = 12.0 g/dL (120 g/L) for men and
= 11.0 g/dL (110 g/L) for women.
22) Creatinine kinase (CK ) = 3X ULN.
23) Subjects that have an abnormal TSH value at screening will be further evaluated by free T4. Subjects with an abnormal T4 will be excluded.
24) Clinically significant (CS) abnormalities in any pre-randomization laboratory
analyses or ECG that, in the Investigator’s opinion, would preclude randomization.
25) Subjects who have contraindications to therapy as outlined in the Saxagliptin
Investigator Brochure or local metformin IR package insert.
26) Subjects with known contraindications to DPP-IV therapy.
27) Treatment with potent systemic cytochrome P450 3A4 (CYP3A4) inducers
28) History of administration of any antihyperglycemic therapy (other than metformin IR as applica
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary endpoint is the change in A1C from baseline to Week 12 (or the last post<br>baseline measurement prior to Week 12, if no Week 12 assessment is available). The<br>primary comparison is between the saxagliptin 2.5 mg BID (plus stable background<br>metformin IR) and placebo (plus stable background metformin IR) treatment groups.;Secondary Objective: Comparison of saxagliptin 2.5 mg or placebo in combination with metformin IR<br>following 12 weeks of double-blind therapy for the following secondary objectives:<br>1. The mean change from baseline in FPG.<br>2. The proportion of subjects who will achieve a therapeutic glycemic response<br>defined as A1C < 7.0%.<br>3. The proportion of subjects who will achieve a therapeutic glycemic response<br>defined as A1C = 6.5%;Primary end point(s): Change in A1C level from baseline to Week 12, (or the last post baseline measurement prior to Week 12, if no Week 12 assessment is available)
- Secondary Outcome Measures
Name Time Method