Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Efficacy and Safety of Alogliptin Plus Metformin Compared to Glipizide Plus Metformin in Patients With Type 2 Diabetes Mellitus (ENDURE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT00856284
First received: March 4, 2009
Last updated: September 25, 2013
Last verified: September 2013

March 4, 2009
September 25, 2013
March 2009
October 2012   (final data collection date for primary outcome measure)
  • Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    The change from Baseline to Week 52 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). The least squares (LS) means are from an analysis of covariance (ANCOVA) model with treatment, study schedule, and geographic region as class variables, and Baseline metformin dose and Baseline HbA1c as covariates.
  • Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 104 [ Time Frame: Baseline and Week 104 ] [ Designated as safety issue: No ]
    The change from Baseline to Week 104 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). The least squares (LS) means are from an analysis of covariance (ANCOVA) model with treatment, study schedule, and geographic region as class variables, and Baseline metformin dose and Baseline HbA1c as covariates.
Change from Baseline in Glycosylated Hemoglobin. [ Time Frame: Week 52 or Week 104. ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00856284 on ClinicalTrials.gov Archive Site
  • Change From Baseline in Glycosylated Hemoglobin at Other Time Points [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 26, 39, 65, 78, and 91. ] [ Designated as safety issue: No ]
    The change from Baseline over time in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). LS means are from an ANCOVA model with treatment, study schedule, and geographic region as class variables, and Baseline metformin dose and Baseline HbA1c as covariates.
  • Change From Baseline in Fasting Plasma Glucose Over Time [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 26, 39, 52, 65, 78, 91, and 104. ] [ Designated as safety issue: No ]
    The change from Baseline in fasting plasma glucose (FPG) was assessed at Weeks 2, 4, 8, 12, 16, 20, 26, 39, 52, 65, 78, 91, and 104. LS means are from an ANCOVA model with treatment, study schedule, and geographic region as class variables, and Baseline FPG and Baseline metformin dose as covariates.
  • Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 6.5% [ Time Frame: Weeks 26, 52, 78, and 104. ] [ Designated as safety issue: No ]
    The percentage of participants with HbA1c less than or equal to 6.5% at Weeks 26, 52, 78, and 104. Participants who did not complete the scheduled Week 104 visit were assessed based on their response at the time of discontinuation.
  • Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.0% [ Time Frame: Weeks 26, 52, 78, and 104. ] [ Designated as safety issue: No ]
    Percentage of participants with HbA1c ≤ 7.0% at Weeks 26, 52, 78, and 104. Participants who did not complete the scheduled Week 104 visit were assessed based on their response at the time of discontinuation.
  • Change From Baseline in Body Weight Over Time [ Time Frame: Baseline and Weeks 12, 26, 39, 52, 65, 78, 91, and 104. ] [ Designated as safety issue: No ]
    LS Means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and Baseline weight and Baseline metformin dose as covariates.
  • Change from Baseline in Glycosylated Hemoglobin. [ Time Frame: Weeks 4, 8, 12, 16, 20, 26, 39, 65, 78, and 91. ] [ Designated as safety issue: No ]
  • Change from Baseline in Fasting Plasma Glucose. [ Time Frame: Weeks 2, 4, 8, 12, 16, 20, 26, 39, 52, 65, 78, 91, and 104. ] [ Designated as safety issue: No ]
  • Incidence of Glycosylated Hemoglobin less than or equal to 6.5% [ Time Frame: Weeks 26, 52, 78, and 104. ] [ Designated as safety issue: No ]
  • Incidence of Glycosylated Hemoglobin less than to 7.0% [ Time Frame: Weeks 26, 52, 78, and 104. ] [ Designated as safety issue: No ]
  • Change from Baseline in Body Weight [ Time Frame: Weeks 12, 26, 39, 52, 65, 78, 91, and 104. ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Efficacy and Safety of Alogliptin Plus Metformin Compared to Glipizide Plus Metformin in Patients With Type 2 Diabetes Mellitus
A Multicenter, Randomized, Double-Blind, Active-Controlled Study to Evaluate the Durability of the Efficacy and Safety of Alogliptin Compared to Glipizide When Used in Combination With Metformin in Subjects With Type 2 Diabetes

The purpose of this study is to determine the safety and effectiveness of adding alogliptin, once daily (QD), compared to glipizide with metformin in diabetic patients.

For patients diagnosed with type 2 diabetes mellitus, metformin is the usual first-line therapy in addition to diet control and exercise. For those patients with inadequate glycemic control with metformin monotherapy or experiencing serious side effects of metformin, sulfonylurea is a popular choice as a second-line oral antidiabetic treatment.

Alogliptin is a dipeptidyl peptidase-4 inhibitor currently being developed by Takeda for use in patients with type 2 diabetes mellitus.

This study is designed to further explore the durability of efficacy and safety of alogliptin compared to glipizide in type 2 diabetes mellitus patients whose blood sugar level is inadequately controlled with metformin therapy.

The duration of this study will be approximately 2 years.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Type 2 Diabetes Mellitus
  • Drug: Alogliptin
    Alogliptin tablets
    Other Names:
    • SYR-322
    • Nesina
  • Drug: Metformin
    Metformin tablets
    Other Name: Glucophage
  • Drug: Glipizide
    Glipizide tablets
    Other Name: Glucotrol
  • Experimental: Metformin + Alogliptin 12.5 mg
    Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
    Interventions:
    • Drug: Alogliptin
    • Drug: Metformin
  • Experimental: Metformin + Alogliptin 25 mg
    Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
    Interventions:
    • Drug: Alogliptin
    • Drug: Metformin
  • Active Comparator: Metformin + Glipizide
    Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.
    Interventions:
    • Drug: Metformin
    • Drug: Glipizide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
2639
October 2012
October 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Has a diagnosis of type 2 diabetes mellitus.
  • Must meet one of the following:

    • Has been inadequately controlled on a stable daily dose of ≥1500 mg (or documented maximum tolerated dose) of metformin for at least 2 months prior to Screening.
    • Has been inadequately controlled (as defined by a glycosylated hemoglobin 7.5 - 10%, inclusive) on metformin <1500 mg without documented maximum tolerated dose.
  • No treatment with antidiabetic agents other than metformin within 2 months prior to Screening (for Schedule A)/Pre-Screening (for Schedule B).
  • Has body mass index within 23 kg/m^2 and 45 kg/m^2 unless the patient is Asian or of Asian descent, for whom the allowable body mass index will be ≥ 20 kg/m^2 and ≤ 35 kg/m^2, inclusive.
  • Has fasting C-peptide concentration at least 0.8 ng.
  • If regularly using non-excluded medications, must be on a stable dose at least 4 weeks prior to Screening/Pre-screening.
  • Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant, lactating or intends to donate ova from Screening throughout the duration of the study.
  • Must be able and willing to monitor their blood glucose concentrations with a home monitor, and comply with protocol requirements including scheduled clinic appointments.

Exclusion Criteria:

  • Systolic blood pressure greater than or equal to 150 mmHg and/or diastolic pressure greater than or equal to 90.
  • Hemoglobin less than or equal to 12 g/dL for males and less than or equal to 10 g/dL for females at Screening Visit.
  • Alanine aminotransferase greater than or equal to 2.5 times the upper limit of normal at Screening Visit.
  • Serum creatinine greater than or equal to 1.5 mg/dL for males and 1.4 for females, or calculated creatinine clearance less than 60 L/min.
  • Males intending to impregnate others or donate sperm before, during or within 1 month after participating in the study.
  • A history of cancer other than squamous or basal cell carcinoma of the skin that has not been in full remission for at least 5 years.
  • A history of laser treatment for diabetic retinopathy within 6 months of screening.
  • Treated for diabetic gastric paresis, gastric banding, or gastric bypass.
  • New York Heart Association Class III or IV heart failure.
  • History of coronary angioplasty, coronary stent placement, coronary bypass surgery, myocardial infarction, stroke or transient ischemic attack within 3 months prior to screening.
  • Known history of human immunodeficiency virus, hepatitis B or C.
  • Alcohol or substance abuse within 2 years prior to screening.
  • Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

    • Any investigational drug within 30 days
    • Any investigational diabetic drug within 3 months
    • Any antidiabetic drug in the dipeptidyl peptidase-4 inhibitors or glucagon-like peptide-1 mimetics classes within 90 days prior to Screening other than metformin
    • Prior treatment with alogliptin.
    • Weight-loss drugs
    • Oral or systemically injected glucocorticoids
  • A hypersensitivity allergy or anaphylactic reaction to any dipeptidyl peptidase-4 drug, metformin or glipizide.
  • Has a documented history or concurrent signs of significant thyroid disease (eg, autoimmune thyroid diseases such as Graves disease and Hashimoto thyroiditis or active thyroid nodules).
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Australia,   Austria,   Brazil,   Canada,   Chile,   Germany,   Guatemala,   Hong Kong,   Hungary,   India,   Israel,   Italy,   Korea, Republic of,   Latvia,   Lithuania,   Malaysia,   Mexico,   New Zealand,   Peru,   Philippines,   Poland,   Puerto Rico,   Romania,   Russian Federation,   Singapore,   South Africa,   Spain,   Thailand,   Ukraine,   United Kingdom
 
NCT00856284
SYR-322_305, 2008-007444-34, U1111-1111-7397, HKCTR-862, DOH-27-0709-2825, 09/H0703/66, NMRR-09-203-3590
Yes
Takeda
Takeda
Not Provided
Study Director: Medical Director, Clinical Science Takeda
Takeda
September 2013

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