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Completed

NCT Number: NCT00757588

Safety and Efficacy of Saxagliptin Plus Insulin With or Without Metformin

The purpose of this study is to compare the effects of saxagliptin with those of placebo as add-on therapy to insulin and insulin with metformin in improving glycemic control at 24 and 52 weeks.

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Key information

Conditions

Type 2 Diabetes Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–78 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Local Institution, Calgary, Alberta, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Type 2 diabetes mellitus
  • Must have been taking a stable dose of basal or premixed insulin for 8 weeks or longer prior to screening
  • If taking metformin, must have been taking the same daily dose for 8 weeks or longer prior to screening
  • Insulin type should be intermediate- or long-acting (basal) or premixed (premixed formulation may include short- or rapid-acting insulin as 1 component).
  • Inadequate glycemic control (A1C of 7.5% to 11.0%, inclusive)
  • Body mass index of 45 kg/m² or lower
  • Fasting C-peptide level of 0.8 ng/mL or higher

Exclusion criteria

  • Symptoms of poorly controlled diabetes, including but not limited to marked polyuria and polydipsia with greater than 10% weight loss during the last 3 months prior to screening or other signs and symptoms
  • History of diabetic ketoacidosis or hyperosmolar nonketotic coma
  • Women of childbearing potential unable or unwilling to use acceptable birth control
  • Women who are pregnant or breastfeeding
  • Active liver disease
  • Anemia
  • Chronic or repeated intermittent corticosteroid treatment (participants receiving stable doses of replacement corticosteroid (except dexamethasone) therapy may be enrolled)
  • Use of short- or rapid-acting insulin
  • Significant cardiovascular history defined as: myocardial infarction, coronary angioplasty or bypass graft, valvular disease or repair, unstable angina pectoris, transient ischemic attack, or cerebrovascular accident
  • Congestive heart failure
  • Unstable or rapidly progressing renal disease
  • History of alcohol or drug abuse within the previous year
  • History of hemoglobinopathies
  • Unstable major psychiatric disorders
  • Immunocompromised status

Treatment and study plan

Saxagliptin, 5 mg + insulin

Drug

Saxagliptin, 5-mg tablets (plus stable insulin dose), given orally once daily (24 weeks short-term, 28 weeks long-term); participants stratified by use of stable metformin dose; flexible insulin dose (as needed for rescue)

Other names: BMS-477118

Placebo + insulin

Drug

Placebo tablets given orally once daily for 24 weeks (short-term period)+ insulin with metformin

Primary outcomes

  1. Adjusted Mean Change From Baseline in A1C Levels (Last Observation Carried Forward [LOCF])

    Time frame: Baseline to Week 24

    Change from baseline: post-pre. Adjusted for baseline (value and metformin use). ANCOVA model: difference between week t and baseline values=baseline values + treatment + metformin use

Secondary outcomes

  1. Change From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Meal Tolerance Test (MTT)

    Time frame: Baseline to Week 24

    An MTT is a 2-part test that measures glucose and insulin levels after an overnight fast and before ingesting a meal consisting of a nutritional drink and power bar and again at prespecified times (30, 60, 120, and 180 minutes) after the start of ingestion of the meal

  2. Change From Baseline in 120-minute PPG Values During an MTT

    Time frame: Baseline to Week 24

    An MTT is a 2-part test that measures glucose and insulin levels after an overnight fast and before ingesting a meal consisting of a nutritional drink and power bar and again at prespecified times (30, 60, 120, and 180 minutes) after the start of ingestion of the meal.

  3. Change From Baseline in Fasting Plasma Glucose Values

    Time frame: Baseline to Week 24

  4. Percentage of Participants Achieving a Therapeutic Glycemic Response

    Time frame: Baseline to Week 24

    Therapeutic glycemic response is defined as an A1C<7%. Significance was not interpreted with a p value.

  5. Change From Baseline in Mean Total Daily Dose of Insulin (MTDDI) (LOCF)

    Time frame: Baseline to Week 24

    Based on information recorded in the participant's daily diary. The MTDDI was calculated at every visit using the values patients recorded since the last regularly scheduled visit (minimum of 80% of days with a value). At every visit, the MTDDI was compared with the participant's baseline MTDDI (measured during a 4-week lead-in period) to identify any changes in insulin use at that visit compared with insulin use at baseline.

Other outcomes

  1. Number of Participants With Abnormal Changes From Baseline in Electrocardiogram (ECG) Results

    Time frame: Baseline to Week 52

    ECG abnormalities included those in nonspecific "other" categories (Other nonspecific ST/T, Other intraventricular conduction defect, Other, and Other rhythm abnormalities)and nonspecific findings, such as sinus bradycardia, sinus arrythmia, sinus tachycardia, poor R-wave progression, and ventricular premature contractions.

  2. Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF)

    Time frame: Baseline and Weeks 24 and 52

    Absolute lymphocyte count=value*10^3 c/uL

  3. Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs

    Time frame: Baseline to Week 52, continuously

    An AE is any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; requires inpatient hospitalization; or prolongs existing hospitalization. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study treatment.

  4. Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings

    Time frame: Baseline to Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, 44, and 52

  5. Mean Changes From Baseline in Heart Rate

    Time frame: Baseline to Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, 44, and 52

  6. Shift in Platelet Counts From Baseline to Selected Visits (LOCF)

    Time frame: Baseline and Weeks 24 and 52

    Platelet count=value*10^9 c/L

  7. Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period

    Time frame: Baseline and during and up to 14 days after last dose of study drug (in Week 52)

    Marked abnormality=a laboratory value lying outside the predefined criteria and more extreme (farther from the limit)on-treatment than at baseline. ULN=upper limit of normal; LLN=lower limit of normal; prx=pre-RX=pretreatment.

    Criteria 1: if prx=0 use >=2, if prx=0.5 or 1 use >=3, if prx=2 use 4.

  8. Percentage of Participants With Reported and Confirmed Hypoglycemia

    Time frame: Baseline to Week 52

    Confirmed hypoglycemia=fingerstick glucose measurement of ≤50 mg/dL with associated symptoms/

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study title

A Multicenter, Randomized, Double-Blind, Phase 3 Trial to Evaluate the Efficacy and Safety of Saxagliptin Added to Insulin Monotherapy or to Insulin in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Insulin Alone or on Insulin in Combination With Metformin

Important dates

Study start
2008
Primary completion
2010
Study completion
2010
First posted
Sep 23, 2008
Registry last updated
Jun 1, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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