Outpatient Discharge Therapy With Saxagliptin+MetforminXR vs GlipizideXL for Type 2 Diabetes With Severe Hyperglycemia

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2010 by John H. Stroger Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by:
John H. Stroger Hospital
ClinicalTrials.gov Identifier:
NCT01267448
First received: December 27, 2010
Last updated: April 15, 2011
Last verified: December 2010

December 27, 2010
April 15, 2011
December 2010
December 2012   (final data collection date for primary outcome measure)
The proportion of responders in each arm. Responder: FBG 70-300 and/or PPBG <400 mg/dl (week1-6), FBG 70-250 and/or PPBG <300 mg/dl (week 7-12) and without metabolic exclusion criteria, repeat ED visits, hospitalization or significant hypoglycemia. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Non-responder:1 FBG >300 and/or PPBG >400 mg/dl (week 1-6) and FBG >250 and/or PPBG >300 mg/dl in 4 consecutive readings or more (week 7-12).

2. A single confirmed BG of >450 mg/dl. 3. Significant hypoglycemia: Single episode of hypoglycemia with BG < 50 mg/dl or 2 episodes of BG between 50 and 70 mg/dl within 7 days or any episode of symptomatic hypoglycemia.

4. Persistently positive large ketones in urine and/or electrolyte imbalances. 5. Revisit to ED or admission to hospital because of hypoglycemia or uncontrolled hyperglycemia.

To evaluate the stabilization of the blood glucose levels in patients presenting with severe hyperglycemia and prevent development of acute metabolic complications [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
The primary outcome will be analyzed using the intention to treat analysis. The comparison of responders (patients achieving glycemic targets: (Week 1 to 6: FBG or pre-prandial glucose 70 to 300 mg/dl and/or PPBG <400 mg/dl. Week 7 to 12: FBG 70 to 250 mg/dl and/or PPBG <300 mg/dl.) and without meeting exclusion criteria for metabolic complications, need for ED visits, hospitalization or significant hypoglycemia. ) and non-responders will be done by chi-square analysis and predictors of response will be evaluated by logistic regression analysis.
Complete list of historical versions of study NCT01267448 on ClinicalTrials.gov Archive Site
  • Proportion of patients achieving FBG goal of 70-130 mg/dl at 12 weeks in the 2 treatment arms [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

    The rate of decline in BG values (mg/dl) in the two groups over the period of twelve weeks will be analyzed using a mixed model (with random intercept) as a sensitivity analysis.

    The Kaplan-Meier (KM) curves, area under the curve,t-test and chi-square analysis will be used for analysis.

  • Percentage of patients with symptomatic hypoglycemia [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Hypoglycemia and hospitalization rates will be compared between the 2 groups using either chi-square or Fisher exact test will be used. Binary logistic regression will be used to further analysis to identify predictors of hypoglycemia.
  • To measure percentage compliance with medication in the two treatment arms. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Medication compliance will be assessed by pill counting. Each patient will assigned a percentage compliance and the study groups will be compared using independent two sample t-test.
  • The number of fold increase in beta cell function in the 2 arms. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    The early insulin response (EIR) will be calculated as the ratio of insulin to glucose response at 0 and 30 minutes (ΔI30pmol/l/ΔG30mmol/l,). The homeostasis model assessment to assess basal insulin secretion (HOMA-β cell) and insulin resistance (HOMA-IR) will be calculated. The beta cell response to OGTT will be calculated as area under the curve for glucose and insulin at 0, 30 and 60 minutes using the trapezoid rule.
  • To achieve glycemic targets (preprandial BG 70-130 mg/dl) in a significant percentage of patients by the end of the study. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

    The rate of decline in BG values in the two groups over the period of twelve weeks will be analyzed using a mixed model (with random intercept) as a sensitivity analysis.

    The Kaplan-Meier (KM) curves, area under the curve,t-test and chi-square analysis.

  • To evaluate the incidence of hypoglycemia in both study group. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Hypoglycemia and hospitalization rates will be compared between the 2 groups using either chi-square or Fisher exact test will be used. Binary logistic regression will be used to further analysis to identify predictors of hypoglycemia.
  • To measure patient compliance with medication. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Medication compliance will be assessed by pill counting. Each patient will assigned a percentage compliance and the study groups will be compared using independent two sample t-test.
Not Provided
Not Provided
 
Outpatient Discharge Therapy With Saxagliptin+MetforminXR vs GlipizideXL for Type 2 Diabetes With Severe Hyperglycemia
A Pilot Study of Outpatient Discharge Therapy With Saxagliptin + Metformin XR or Sulphonylurea for Recently Diagnosed Type 2 Diabetes Presenting With Severe Hyperglycemia

Saxagliptin + Metformin XR (S+M) will be effective in stabilizing blood glucose (BG) levels in patients with newly diagnosed type 2 diabetes (T2DM) with severe hyperglycemia (BG levels 300 to 450 mg/dl) and glucose toxicity and with no criteria for inpatient admission or occurrence of severe hypoglycemia compared to glipizide XL.

The study may provide preliminary evidence to support the role of S+M as a bridging, stabilizing and safe therapy in patients with severe hyperglycemia

There is very little information regarding diabetes discharge regimens for patients with recently diagnosed diabetes (<1 year duration) who present with severe hyperglycemia (blood glucose 300-450 mg/dl) to the ED or other clinical settings and who do not need to be admitted.

A combination of Saxagliptin+Metformin XR, could be a potential drug combination to be tested as an initial treatment in these circumstances compared to Glipizide XL which was shown to be effective in our previous study. We expect Saxagliptin to improve beta cell function and decrease glucagon levels as was shown for the DPP-IV class medications and in turn improve blood glucose levels, while Metformin XR may reduce insulin resistance and hepatic glucose output. Such discharge therapy may help to prevent deterioration into acute metabolic complications (DKA or hyperosmolar states) and avoid hospitalization. A high proportion of patients may achieve glycemic targets without significant hypoglycemia as measured by self glucose monitoring and objectively by continuous glucose monitoring system (CGMS). Such an easy regimen may safely bridge the time gap until patients will be seen by their providers.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Diabetes Mellitus Type 2
  • Severe Hyperglycemia - Blood Glucose Level >300mg/dl.
  • Drug: Glipizide XL
    The control group will receive Glipizide XL (10mg orally) for a total duration of 12 weeks.
    Other Name: Glucotrol XL
  • Drug: Saxagliptin + Metformin XR
    The intervention group will receive Saxagliptin 5 mg daily for a total duration of 12 weeks.
    Other Name: Onglyza
  • Drug: Metformin XR
    The intervention group will receive Metformin XR 1000 mg daily and will be automatically titrated weekly in 2 weeks to Metformin XR 2000 daily for a total duration of 12 weeks.
    Other Name: Glucophage XR
  • Active Comparator: Saxagliptin + Metformin XR
    Saxagliptin 5 mg + Metformin XR 1000 mg will be automatically titrated weekly in 2 weeks to Saxagliptin 5 mg + Metformin XR 2000 daily for a total duration of 12 weeks.
    Interventions:
    • Drug: Saxagliptin + Metformin XR
    • Drug: Metformin XR
  • Active Comparator: the Control goup Glipizide XL
    The control group will receive Sulphonylurea (Glipizide XL 10mg orally) for a total duration of 12 weeks.
    Intervention: Drug: Glipizide XL
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
December 2012
December 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Target Population

    1. Subjects recently diagnosed with T2DM (less than 1 year duration) who are either drug naïve or who had not taken oral anti-diabetic agents or insulin for more than 2 weeks.
    2. FBG and or RBG > 300mg/dl and < 450mg/dl
  2. Age and Sex

    1. Men and women aged 18 to 75 years of age.
    2. 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 study drug to minimize the risk of pregnancy.

WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of the investigational product.

Exclusion Criteria:

  1. Sex and Reproductive Status

    1. WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks after the last dose of study drug.
    2. Women who are pregnant or breastfeeding.
    3. Women with a positive pregnancy test.
    4. Sexually active fertile men not using effective birth control if their partners are WOCBP.
  2. Target Disease Exceptions

    1. Type 2 diabetes with weight less than 120 pounds
    2. Type 1 diabetes
    3. History of diabetic ketoacidosis or hyperosmolar nonketotic coma
  3. Medical History and Concurrent Diseases

    1. Age >75 years
    2. History of congestive heart failure
    3. Evidence of an impaired sensorium and/or dementia
    4. Current history of alcohol or substance abuse
    5. Patients with any acute or active chronic medical illness
  4. Physical and Laboratory Test Findings

    1. FBG and /or RGB < 300 mg/dl or >450 mg/dl
    2. Unstable vitals signs (temperature >101 degrees Fahrenheit, systolic blood pressure <90 or >180 mmhg, diastolic blood pressure <60 or >110 mmhg, heart rate <60 or >120 beats/minute)
    3. Electrolyte imbalances (serum bicarbonate level <20 mEq/L, serum sodium <125 or >150 mEq/L, serum potassium <3.5 or >5.5 mEq/L), serum creatinine more than 1.5 in males and 1.4 in females, creatinine clearance less than 60ml/min, liver enzymes 3 times above upper limit of normal range.
    4. HbA1c > 12% (based on our previous study (4) patients with HbA1c of >12 had a high rate of non-responders)
    5. Liver enzymes 3 times above upper limit of normal range.
    6. Allergies and Adverse Drug Reactions -Subjects with a history of any serious hypersensitivity reaction to saxagliptin, glipizide or metformin XR.
  5. Prohibited Treatments and/or Therapies

    a)Treatment with systemic cytochrome P450 3A4 (CYP 3A4) inhibitors.

  6. Other Exclusion Criteria

    1. Prisoners or subjects who are involuntarily incarcerated.
    2. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
Both
18 Years to 75 Years
No
United States
 
NCT01267448
IRB-10-182
Yes
Ambika Babu MD, John H. Stroger Junior Hospital of Cook County, Division of Endocrinology
John H. Stroger Hospital
Bristol-Myers Squibb
Principal Investigator: Ambika Babu, MD,MS John H Stroger Hospital of Cook County
John H. Stroger Hospital
December 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP