A Multicenter, Randomized, Double-Blind, Phase 3b Trial to Evaluate the Efficacy andSafety of Saxagliptin Added to Insulin Monotherapy or to Insulin in Combination withMetformin in Subjects with Type 2 Diabetes Who Have Inadequate Glycemic Control on Insulin Alone or on Insulin in Combination with MetforminRevised Protocol 02 incorporating Protocol Amendment 02 (v1.0, 15-Dec-2008) and Protocol Amendment 03 (v1.0, 04-Nov-2009) + Pharmacogenetics Blood Sample Protocol Amendment 1 (v1.0, 13-Aug-2008)

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

• Registration Number: EUCTR2008-001089-10-HU
• Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-12-12
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1082

Inclusion Criteria

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 dose of insulin (= 30 units/day, = 150 units/day) with
= 20% variation in total daily dose for = 8 weeks prior to screening, with only
occasional exceptions (= one day/week). For example, if the subject is taking
50 units/day of insulin, the total daily doses in the past 8 weeks should not have
exceeded 60 units, or been less than 40 units. However, occasional deviations (= one
day/week) during this time period are permitted.
4) Subjects’ insulin type should be intermediate-acting or long-acting (basal) or
pre-mixed (pre-mixed formulation may include short- or rapid-acting insulin as one
component).
5) Among subjects taking metformin, subjects should have been taking the same daily dose of metformin for = 8 weeks prior to screening, if applicable.
6) A1C measured at screening = 7.5% and = 11.0%. Note that A1C will be re-checked
near the end of the lead-in period, at Day -5, and must again be = 7.5% and = 11.0%
for subject to be randomized.
7) Fasting C-peptide = 0.8 ng/mL (= 0.26 nmol/L).
8) Body mass index = 45 kg/m²
9) Men and women, ages 18 to 78 (inclusive).
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
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) WOCBP who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study period.
2) WOCBP using a prohibited contraceptive method.
3) Women who are pregnant or breastfeeding
4) Women with a positive pregnancy test on enrollment or prior to investigational
product administration.
5) 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 last three months prior to screening or other signs and
symptoms.
6) History of diabetic ketoacidosis or hyperosmolar nonketotic coma.
7) Significant cardiovascular history defined as:
a) within six months prior to screening, subject has had history of myocardial
infarction, coronary angioplasty or bypass graft(s), valvular disease or repair,
unstable angina pectoris, transient ischemic attack, or cerebrovascular accident.
b) Congestive heart failure defined as New York Heart Association (NYHA) stage
III and IV (see Appendix 3) and /or known left ventricular ejection fraction of < 40%.
8) Chronic or repeated intermittent corticosteroid treatment (subjects receiving stable doses of replacement corticosteroid (except dexamethasone) therapy may be
enrolled).
9) History of unstable or rapidly progressing renal disease.
10) History of alcohol or drug abuse within the previous year.
11) Unstable major psychiatric disorders.
12) Immunocompromised individuals such as subjects that have undergone organ
transplantation or subjects diagnosed with human immunodeficiency virus.
13) History of hemoglobinopathies (sickle cell anemia or thalassemias, sideroblastic
anemia).
14) Donation of blood or plasma to a blood bank within three months of screening.
15) Administration of any other investigational drug or participation in a clinical research trial within 30 days of entry into Lead-in Period to this study.
16) 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.
17) Active liver disease and/or significant abnormal liver function defined as AST > 2x
ULN and/or ALT > 2x ULN and / or serum total bilirubin > 2.0 mg/dL (34.2 micromoles/L).
18) 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 (ie indicating immunity to hepatitis B infection or previous vaccination) may be
included.
19) Serum creatinine (Scr) = 1.5 mg/dL (132.6 µmol/L) for males and = 1.4 mg/dL
(123.8 µmol/L) for females, or calculated creatinine clearance (by Cockcroft-Gault
equation) < 60 ml/min.
20) Creatine Kinase = 3x ULN.
21) 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.
22) 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.
23) Subjects who have contraindications to therapy as outlined in the Saxagliptin
Investigator Brochure or insulin or metformin (if applicable) package inserts.
24) Subject is using short- or rapid-acting insulin that is not part of a pre-mixed
formulation.
25) History of administration of any antihyperglycemic therapy (other than metformin, if applicable, or insulin) for more than 3 consecutive days or seven non-consecutive days during the eight weeks prior to screening.
26) Use o

Study & Design

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