A 4-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial toEvaluate The Efficacy and Safety of Saxagliptin in Comparison to Placebo as Add-onTreatment to Metformin XR in Subjects with Type 2 Diabetes who have InadequateGlycemic Control with Diet and Exercise and a Stable Dose of Metformin XR= 1500 mg/dayRevised Protocol 01 incorporating Protocol Amendment 01 (v1.0, dated 24-Jul-2008).

• Conditions: type 2 diabetes; MedDRA version: 9.1Level: LLTClassification code 10063624Term: Type II diabetes mellitus inadequate control

• Registration Number: EUCTR2008-000976-26-SE
• Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-07-28
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

1) Signed Written Informed Consent
a) Subjects must be willing and able to give written informed consent.
2) Target Population
a) Subjects with a diagnosis of type 2 diabetes mellitus requiring treatment with at
least 1500 mg, but not greater than 2550 mg of a stable dose of metformin IR or
XR as monotherapy for at least 8 weeks prior to screening are eligible
b) A1C = 7% and = 10% obtained at the screening visit.
c) Fasting C-peptide concentration = 1.0 ng/ml at the screening visit.
d) Body mass index = 40 kg/m2 at the screening visit.
3) Age and Sex
a) Men and women, ages 18 to 77 years of age.
Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study and for up to 4 weeks after
the last dose of investigational product 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.
Women who are using oral contraceptives, other hormonal contraceptives
(vaginal products, skin patches, or implanted or injectable products), or
mechanical products such as an intrauterine device or barrier methods
(diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing
abstinence or where their partner is sterile (eg, vasectomy) should be considered
to be of childbearing potential.
WOCBP must have a negative serum or urine pregnancy test (minimum
sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start
of investigational product.
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) Sex and Reproductive Status
a) WOCBP who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study and for up to 4 weeks after the last dose of
investigational product.
b) WOCBP using a prohibited contraceptive method.
c) Women who are pregnant or breastfeeding.
d) Women with a positive pregnancy test on enrollment or prior to investigational
product administration.

2) Target Disease Exceptions
a) Symptoms of poorly controlled diabetes that would preclude participation in this
placebo-controlled trial including but not limited to marked polyuria and
polydipsia with greater than 10% weight loss during the last three months prior to
screening or other signs and symptoms.
b) History of diabetic ketoacidosis or hyperosmolar nonketotic coma.
c) Insulin therapy within one year of screening (with the exception of insulin therapy
during a hospitalization or use in gestational diabetes.

3) Medical History and Concurrent Diseases
a) Significant cardiovascular history defined as:
i) History of myocardial infarction, coronary angioplasty or bypass graft(s),
valvular disease or repair, unstable angina pectoris, transient ischemic attack,
or cerebrovascular accidents within six months prior to study entry.
ii) Congestive heart failure defined as New York Heart Association (NYHA)
stage III and IV and/or known left ventricular ejection fraction of = 40%.
b) Chronic or repeated intermittent corticosteroid treatment (subjects receiving stable doses of replacement corticosteroid therapy may be enrolled).
c) History of unstable or rapidly progressing renal disease.
d) History of alcohol or drug abuse within the previous one year.
e) Unstable major psychiatric disorders.
f) Immunocompromised individuals such as subjects who have undergone organ
transplantation or subjects diagnosed with human immunodeficiency virus.
g) History of hemoglobinopathies (sickle cell anemia or thalassemias, sideroblastic
anemia).
h) Donation of blood or plasma to a blood bank within three months of screening.
i) Administration of any other investigational drug or participation in a clinical
research trial within 30 days of planned enrollment to this study.
j) Any condition which in the Investigator’s opinion may render the subject unable
to complete the study or which may pose significant risk to the subject.

4) Physical and Laboratory Test Findings
a) Active liver disease and/or significant abnormal liver function defined as AST
> 2 x ULN and/or ALT > 2x ULN and /or serum total bilirubin > 2.0 mg/dl.
b) 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.
c) Serum creatinine (Scr) = 1.5 mg/dl (132.6 µmol/L) for males and = 1.4 mg/dl
(123.8 µmol/L) for females.
d) Creatine Kinase = 3x ULN.
e) Anemia, of any etiology defined as hemoglobin = 12.0 g/dL (120 g/L) for men
and hemoglobin = 11.0 g/dL (110 g/L) for women.
f) Subjects who have an abnormal TSH value at screening will be further evaluated
by free T4. Subjects with an abnormal free T4 will be excluded.

5) Allergies and Adverse Drug Reactions
a) Subjects who have contraindications to therapy as outlined in the Saxagliptin
Investigator Brochure, metformin XR/metformin package insert package insert.

6) Prohibited Therapies and/or Medications
a) History of administration of any antihyperglycemic therapy (other than a 1500 mg
to 2550 mg maximum daily dose

Study & Design

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