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

Overview[ - collapse ][ - ]

Purpose 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
ConditionDiabetes Mellitus Type 2
Severe Hyperglycemia - Blood Glucose Level >300mg/dl.
InterventionDrug: Glipizide XL
Drug: Saxagliptin + Metformin XR
Drug: Metformin XR
PhasePhase 4
SponsorJohn H. Stroger Hospital
Responsible PartyJohn H. Stroger Hospital
ClinicalTrials.gov IdentifierNCT01267448
First ReceivedDecember 27, 2010
Last UpdatedApril 15, 2011
Last verifiedDecember 2010

Tracking Information[ + expand ][ + ]

First Received DateDecember 27, 2010
Last Updated DateApril 15, 2011
Start DateDecember 2010
Estimated Primary Completion DateDecember 2012
Current Primary Outcome MeasuresThe 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.
Current Secondary Outcome Measures
  • 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.

Descriptive Information[ + expand ][ + ]

Brief TitleOutpatient Discharge Therapy With Saxagliptin+MetforminXR vs GlipizideXL for Type 2 Diabetes With Severe Hyperglycemia
Official TitleA Pilot Study of Outpatient Discharge Therapy With Saxagliptin + Metformin XR or Sulphonylurea for Recently Diagnosed Type 2 Diabetes Presenting With Severe Hyperglycemia
Brief Summary
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
Detailed Description
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.
Study TypeInterventional
Study PhasePhase 4
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition
  • Diabetes Mellitus Type 2
  • Severe Hyperglycemia - Blood Glucose Level >300mg/dl.
InterventionDrug: Glipizide XL
The control group will receive Glipizide XL (10mg orally) for a total duration of 12 weeks.
Other Names:
Glucotrol XLDrug: Saxagliptin + Metformin XR
The intervention group will receive Saxagliptin 5 mg daily for a total duration of 12 weeks.
Other Names:
OnglyzaDrug: 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 Names:
Glucophage XR
Study Arm (s)
  • 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.
  • Active Comparator: the Control goup Glipizide XL
    The control group will receive Sulphonylurea (Glipizide XL 10mg orally) for a total duration of 12 weeks.

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment100
Estimated Completion DateDecember 2012
Estimated Primary Completion DateDecember 2012
Eligibility Criteria
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.
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT01267448
Other Study ID NumbersIRB-10-182
Has Data Monitoring CommitteeYes
Information Provided ByJohn H. Stroger Hospital
Study SponsorJohn H. Stroger Hospital
CollaboratorsBristol-Myers Squibb
Investigators Principal Investigator: Ambika Babu, MD,MS John H Stroger Hospital of Cook County
Verification DateDecember 2010

Locations[ + expand ][ + ]

John Stroger Hospital of Cook County
Chicago, Illinois, United States, 60612
Contact: Ambika Babu, M.D. | 312-864-0543 | Ambika_Babu@rush.edu
Principal Investigator: Ambika Babu, M.D.
Not yet recruiting
John Stroger Hospital of Cook County
Chicago, Illinois, United States, 60612
Contact: Ambika Babu, M.D. | 312-864-0543 | aamblee@hotmail.com
Principal Investigator: Ambika Babu, M.D.
Recruiting