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
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Alogliptin
Drug: Metformin
Drug: Glipizide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 2639
Study Start Date: March 2009
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Alogliptin
Alogliptin tablets
Other Names:
  • SYR-322
  • Nesina
Drug: Metformin
Metformin tablets
Other Name: Glucophage
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.
Drug: Alogliptin
Alogliptin tablets
Other Names:
  • SYR-322
  • Nesina
Drug: Metformin
Metformin tablets
Other Name: Glucophage
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.
Drug: Metformin
Metformin tablets
Other Name: Glucophage
Drug: Glipizide
Glipizide tablets
Other Name: Glucotrol

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00856284

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Amphure Muang, Thailand
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Dnepropertovsk, Ukraine
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Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director, Clinical Science Takeda
  More Information

No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00856284     History of Changes
Other Study ID Numbers: SYR-322_305, 2008-007444-34, U1111-1111-7397, HKCTR-862, DOH-27-0709-2825, 09/H0703/66, NMRR-09-203-3590
Study First Received: March 4, 2009
Results First Received: September 25, 2013
Last Updated: September 25, 2013
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Austria: Ethikkommission
Brazil: National Committee of Ethics in Research
Brazil: National Health Surveillance Agency
Canada: Health Canada
Chile: Instituto de Salud Pública de Chile
Dominican Republic: Secretaría del Estado de Salud Pública y Asistencia Social (SESPAS)
Hong Kong: Department of Health
Hong Kong: Joint CUHK-NTEC Clinical Research Ethics Committee
Hungary: National Institute of Pharmacy
Israel: Ethics Commission
Italy: Ministry of Health
Malaysia: Ministry of Health
Mexico: Ethics Committee
Mexico: Federal Commission for Protection Against Health Risks
Mexico: Federal Commission for Sanitary Risks Protection
Mexico: Ministry of Health
New Zealand: Health and Disability Ethics Committees
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Peru: Ministry of Health
Philippines: Department of Health
Philippines: Bureau of Food and Drugs
Poland: Ministry of Health
Romania: Ethics Committee
Russia: Ministry of Health of the Russian Federation
South Africa: Department of Health
South Korea: Institutional Review Board
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Ethics Committee
Thailand: Ethical Committee
Thailand: Ministry of Public Health
Ukraine: Ministry of Health
United Kingdom: Research Ethics Committee

Keywords provided by Takeda:
Diabetes Mellitus
Drug Therapy
Hyperinsulinism
Hyperglycemia
Glucose Intolerance

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Alogliptin
Glipizide
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2014