Study of Alogliptin Combined With Sulfonylurea in Subjects With Type 2 Diabetes Mellitus.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT00286468
First received: February 1, 2006
Last updated: February 1, 2012
Last verified: February 2012
  Purpose

The purpose of this study is to evaluate the efficacy and safety of alogliptin, once daily (QD), combined with a sulfonylurea in adults with type 2 diabetes mellitus.


Condition Intervention Phase
Diabetes Mellitus
Drug: Alogliptin and glyburide
Drug: Glyburide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of SYR110322 (SYR-322) When Used in Combination With a Sulfonylurea 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 26. [ Time Frame: Baseline and Week 26. ] [ Designated as safety issue: No ]
    The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 26 or final visit and glycosylated hemoglobin collected at baseline.


Secondary Outcome Measures:
  • Change From Baseline in Glycosylated Hemoglobin (Week 4). [ Time Frame: Baseline and Week 4. ] [ Designated as safety issue: No ]
    The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 4 and Glycosylated Hemoglobin collected at baseline.

  • Change From Baseline in Glycosylated Hemoglobin (Week 8). [ Time Frame: Baseline and Week 8. ] [ Designated as safety issue: No ]
    The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 8 and Glycosylated Hemoglobin collected at baseline.

  • Change From Baseline in Glycosylated Hemoglobin (Week 12). [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: No ]
    The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 12 and Glycosylated Hemoglobin collected at baseline.

  • Change From Baseline in Glycosylated Hemoglobin (Week 16). [ Time Frame: Baseline and Week 16. ] [ Designated as safety issue: No ]
    The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 16 and Glycosylated Hemoglobin collected at baseline.

  • Change From Baseline in Glycosylated Hemoglobin (Week 20). [ Time Frame: Baseline and Week 20. ] [ Designated as safety issue: No ]
    The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 20 and Glycosylated Hemoglobin collected at baseline.

  • Change From Baseline in Fasting Plasma Glucose (Week 1). [ Time Frame: Baseline and Week 1. ] [ Designated as safety issue: No ]
    The change between the value of fasting plasma glucose collected at final visit or week 1 and fasting plasma glucose collected at baseline.

  • Change From Baseline in Fasting Plasma Glucose (Week 2). [ Time Frame: Baseline and Week 2. ] [ Designated as safety issue: No ]
    The change between the value of fasting plasma glucose collected at week 2 and fasting plasma glucose collected at baseline.

  • Change From Baseline in Fasting Plasma Glucose (Week 4). [ Time Frame: Baseline and Week 4. ] [ Designated as safety issue: No ]
    The change between the value of fasting plasma glucose collected at week 4 and fasting plasma glucose collected at baseline.

  • Change From Baseline in Fasting Plasma Glucose (Week 8). [ Time Frame: Baseline and Week 8. ] [ Designated as safety issue: No ]
    The change between the value of fasting plasma glucose collected at week 8 and fasting plasma glucose collected at baseline.

  • Change From Baseline in Fasting Plasma Glucose (Week 12). [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: No ]
    The change between the value of fasting plasma glucose collected at week 12 and fasting plasma glucose collected at baseline.

  • Change From Baseline in Fasting Plasma Glucose (Week 16). [ Time Frame: Baseline and Week 16. ] [ Designated as safety issue: No ]
    The change between the value of fasting plasma glucose collected at week 16 and fasting plasma glucose collected at baseline.

  • Change From Baseline in Fasting Plasma Glucose (Week 20). [ Time Frame: Baseline and Week 20. ] [ Designated as safety issue: No ]
    The change between the value of fasting plasma glucose collected at week 20 and fasting plasma glucose collected at baseline.

  • Change From Baseline in Fasting Plasma Glucose (Week 26). [ Time Frame: Baseline and Week 26. ] [ Designated as safety issue: No ]
    The change between the value of fasting plasma glucose collected at week 26 or final visit and fasting plasma glucose collected at baseline.

  • Number of Participants With Marked Hyperglycemia (Fasting Plasma Glucose ≥ 200 mg Per dL). [ Time Frame: 26 Weeks. ] [ Designated as safety issue: No ]
    The number of participants with a fasting plasma glucose value greater than or equal to 200 mg per dL during the 26 week study.

  • Number of Participants Requiring Rescue. [ Time Frame: 26 Weeks. ] [ Designated as safety issue: No ]
    The number of participants requiring rescue for failing to achieve pre-specified glycemic targets during the 26 week study.

  • Change From Baseline in Fasting Proinsulin (Week 4). [ Time Frame: Baseline and Week 4. ] [ Designated as safety issue: No ]
    The change between the value of fasting proinsulin collected at week 4 and fasting proinsulin collected at baseline.

  • Change From Baseline in Fasting Proinsulin (Week 8). [ Time Frame: Baseline and Week 8. ] [ Designated as safety issue: No ]
    The change between the value of fasting proinsulin collected at week 8 and fasting proinsulin collected at baseline.

  • Change From Baseline in Fasting Proinsulin (Week 12). [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: No ]
    The change between the value of fasting proinsulin collected at week 12 and fasting proinsulin collected at baseline.

  • Change From Baseline in Fasting Proinsulin (Week 16). [ Time Frame: Baseline and Week 16. ] [ Designated as safety issue: No ]
    The change between the value of fasting proinsulin collected at week 16 and fasting proinsulin collected at baseline.

  • Change From Baseline in Fasting Proinsulin (Week 20). [ Time Frame: Baseline and Week 20. ] [ Designated as safety issue: No ]
    The change between the value of fasting proinsulin collected at week 20 and fasting proinsulin collected at baseline.

  • Change From Baseline in Fasting Proinsulin (Week 26). [ Time Frame: Baseline and Week 26. ] [ Designated as safety issue: No ]
    The change between the value of fasting proinsulin collected at week 26 or final visit and fasting proinsulin collected at baseline.

  • Change From Baseline in Insulin (Week 4). [ Time Frame: Baseline and Week 4. ] [ Designated as safety issue: No ]
    The change between the value of insulin collected at week 4 and insulin collected at baseline.

  • Change From Baseline in Insulin (Week 8). [ Time Frame: Baseline and Week 8. ] [ Designated as safety issue: No ]
    The change between the value of insulin collected at week 8 and insulin collected at baseline.

  • Change From Baseline in Insulin (Week 12). [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: No ]
    The change between the value of insulin collected at week 12 and insulin collected at baseline.

  • Change From Baseline in Insulin (Week 16). [ Time Frame: Baseline and Week 16. ] [ Designated as safety issue: No ]
    The change between the value of insulin collected at week 16 and insulin collected at baseline.

  • Change From Baseline in Insulin (Week 20). [ Time Frame: Baseline and Week 20. ] [ Designated as safety issue: No ]
    The change between the value of insulin collected at week 20 and insulin collected at baseline.

  • Change From Baseline in Insulin (Week 26). [ Time Frame: Baseline and Week 26. ] [ Designated as safety issue: No ]
    The change between the value of insulin collected at week 26 and insulin collected at baseline.

  • Change From Baseline in Proinsulin/Insulin Ratio (Week 4). [ Time Frame: Baseline and Week 4. ] [ Designated as safety issue: No ]
    The change between the ratio value of proinsulin and insulin collected at week 4 and the ratio value of proinsulin and insulin collected at baseline.

  • Change From Baseline in Proinsulin/Insulin Ratio (Week 8). [ Time Frame: Baseline and Week 8. ] [ Designated as safety issue: No ]
    The change between the ratio value of proinsulin and insulin collected at week 8 and the ratio value of proinsulin and insulin collected at baseline.

  • Change From Baseline in Proinsulin/Insulin Ratio (Week 12). [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: No ]
    The change between the ratio value of proinsulin and insulin collected at week 12 and the ratio value of proinsulin and insulin collected at baseline.

  • Change From Baseline in Proinsulin/Insulin Ratio (Week 16). [ Time Frame: Baseline and Week 16. ] [ Designated as safety issue: No ]
    The change between the ratio value of proinsulin and insulin collected at week 16 and the ratio value of proinsulin and insulin collected at baseline.

  • Change From Baseline in Proinsulin/Insulin Ratio (Week 20). [ Time Frame: Baseline and Week 20. ] [ Designated as safety issue: No ]
    The change between the ratio value of proinsulin and insulin collected at week 20 and the ratio value of proinsulin and insulin collected at baseline.

  • Change From Baseline in Proinsulin/Insulin Ratio (Week 26). [ Time Frame: Baseline and Week 26. ] [ Designated as safety issue: No ]
    The change between the ratio value of proinsulin and insulin collected at week 26 or final visit and the ratio value of proinsulin and insulin collected at baseline.

  • Change From Baseline in C-peptide (Week 4). [ Time Frame: Baseline and Week 4. ] [ Designated as safety issue: No ]
    The change between the value of C-peptide collected at week 4 and C-peptide collected at baseline.

  • Change From Baseline in C-peptide (Week 8). [ Time Frame: Baseline and Week 8. ] [ Designated as safety issue: No ]
    The change between the value of C-peptide collected at week 8 and C-peptide collected at baseline.

  • Change From Baseline in C-peptide (Week 12). [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: No ]
    The change between the value of C-peptide collected at week 12 and C-peptide collected at baseline.

  • Change From Baseline in C-peptide (Week 16). [ Time Frame: Baseline and Week 16. ] [ Designated as safety issue: No ]
    The change between the value of C-peptide collected at week 16 and C-peptide collected at baseline.

  • Change From Baseline in C-peptide (Week 20). [ Time Frame: Baseline and Week 20. ] [ Designated as safety issue: No ]
    The change between the value of C-peptide collected at week 20 and C-peptide collected at baseline.

  • Change From Baseline in C-peptide (Week 26). [ Time Frame: Baseline and Week 26. ] [ Designated as safety issue: No ]
    The change between the value of C-peptide collected at week 26 or final visit and C-peptide collected at baseline.

  • Number of Participants With Glycosylated Hemoglobin ≤ 6.5%. [ Time Frame: Baseline and Week 26. ] [ Designated as safety issue: No ]
    The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 6.5% during the 26 week study.

  • Number of Participants With Glycosylated Hemoglobin ≤ 7.0%. [ Time Frame: Baseline and Week 26. ] [ Designated as safety issue: No ]
    The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 7.0% during the 26 week study.

  • Number of Participants With Glycosylated Hemoglobin ≤ 7.5%. [ Time Frame: Baseline and Week 26. ] [ Designated as safety issue: No ]
    The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 7.5% during the 26 week study.

  • Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 0.5%. [ Time Frame: Baseline and Week 26. ] [ Designated as safety issue: No ]
    The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 0.5% during the 26 week study.

  • Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.0%. [ Time Frame: Baseline and Week 26. ] [ Designated as safety issue: No ]
    The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 1.0% during the 26 week study.

  • Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.5%. [ Time Frame: Baseline and Week 26. ] [ Designated as safety issue: No ]
    The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 1.5% during the 26 week study.

  • Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 2.0%. [ Time Frame: Baseline and Week 26. ] [ Designated as safety issue: No ]
    The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 2.0% during the 26 week study.

  • Change From Baseline in Body Weight (Week 8). [ Time Frame: Baseline and Week 8. ] [ Designated as safety issue: No ]
    The change between Body Weight measured at week 8 and Body Weight measured at baseline.

  • Change From Baseline in Body Weight (Week 12). [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: No ]
    The change between Body Weight measured at week 12 and Body Weight measured at baseline.

  • Change From Baseline in Body Weight (Week 20). [ Time Frame: Baseline and Week 20. ] [ Designated as safety issue: No ]
    The change between Body Weight measured at week 20 and Body Weight measured at baseline.

  • Change From Baseline in Body Weight (Week 26). [ Time Frame: Baseline and Week 26. ] [ Designated as safety issue: No ]
    The change between Body Weight measured at week 26 or final visit and Body Weight measured at baseline.


Enrollment: 500
Study Start Date: April 2006
Study Completion Date: June 2007
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alogliptin 12.5 mg QD Drug: Alogliptin and glyburide
Alogliptin 12.5 mg, tablets, orally, once daily and glyburide for up to 26 weeks.
Other Names:
  • alogliptin
  • SYR110322
  • SYR-322
Experimental: Alogliptin 25 mg QD Drug: Alogliptin and glyburide
Alogliptin 25 mg, tablets, orally, once daily and glyburide for up to 26 weeks.
Other Names:
  • alogliptin
  • SYR110322
  • SYR-322
Active Comparator: Placebo Drug: Glyburide
Alogliptin placebo-matching tablets, orally, once daily and glyburide for up to 26 weeks.

Detailed Description:

There are approximately 19 million people in the United States who have been diagnosed with diabetes mellitus, of which 90% to 95% are type 2. The prevalence of type 2 diabetes varies among racial and ethnic populations and has been shown to correlate with age, obesity, family history, history of gestational diabetes, and physical inactivity. Over the next decade, a marked increase in the number of adults with diabetes mellitus is expected.

Takeda is developing SYR-322 (alogliptin) for the improvement of glycemic control in patients with type 2 diabetes mellitus. Alogliptin is an inhibitor of the dipeptidyl peptidase IV enzyme. Dipeptidyl peptidase IV is thought to be primarily responsible for the degradation of 2 peptide hormones released in response to nutrient ingestion. It is expected that inhibition of dipeptidyl peptidase IV will improve glycemic (glucose) control in patients with type 2 diabetes.

The aim of the current study is to evaluate the effectiveness of alogliptin in combination with a sulfonylurea in subjects who are inadequately controlled on a sulfonylurea alone. Individuals who participate in this study will be required to commit to a screening visit and up to 14 additional visits at the study center. Study participation is anticipated to be about 34 weeks (or 8.5 months).

  Eligibility

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

Inclusion Criteria

  • Diagnosis of type 2 diabetes mellitus , currently treated with a sulfonylurea alone but experiencing inadequate glycemic control. Should have received the sulfonylurea monotherapy for at least the 3 months prior to Screening; has been on a stable sulfonylurea dose equivalent to at least 10 mg of glyburide (Exception: documented maximum tolerated dose equivalent to less than 10 mg but at least 5 mg glyburide) for at least 8 weeks.
  • No treatment with antidiabetic agents other than a sulfonylurea within the 3 months prior to Screening. (Exception: if a subject has received other antidiabetic therapy for less than 7 days within the 3 months prior to Screening.)
  • Body mass index greater than or equal to 23 kg/m2 and less than or equal to 45 kg/m2.
  • Fasting C-peptide concentration greater than or equal to 0.8 ng/mL. (If this screening criterion is not met, the subject still qualifies if C-peptide is greater than or equal to 1.5 ng/mL after a challenge test.).
  • Glycosylated hemoglobin concentration between 7.0% and 10.0%, inclusive.
  • If regular use of other, non-excluded medications, must be on a stable dose for at least the 4 weeks prior to Screening. However, as needed use of prescription or over-the-counter medications is allowed at the discretion of the investigator.
  • Systolic blood pressure less than or equal to180 mm Hg and diastolic pressure less than or equal to 110 mm Hg
  • Hemoglobin greater than or equal to 12 g per dL for males and greater than or equal to 10 g per dL for females
  • Alanine aminotransferase less than or equal to 3 time the upper limit of normal.
  • Serum creatinine ≤2.0 mg/dL (≤17 micromol/L)
  • Thyroid-stimulating hormone level less than or equal to the upper limit of the normal range and the subject is clinically euthyroid.
  • Neither pregnant nor lactating
  • Female subjects of childbearing potential must be practicing adequate contraception. Adequate contraception must be practiced for the duration of participation in the study.
  • Able and willing to monitor their own blood glucose concentrations with a home glucose monitor.
  • No major illness or debility that in the investigator's opinion prohibits the subject from completing the study.
  • Able and willing to provide written informed consent

Exclusion Criteria

  • Urine albumin to creatinine ratio of greater than 1000 μg per mg at Screening. If elevated, the subject may be rescreened within 1 week.
  • History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 5 years prior to Screening. (A history of treated cervical intraepithelial neoplasia I or cervical intraepithelial neoplasia II is allowed.)
  • History of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening.
  • History of treated diabetic gastric paresis.
  • New York Heart Association Class III or IV heart failure regardless of therapy. Currently treated subjects who are stable at Class I or II are candidates for the study.
  • History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within the 6 months prior to Screening.
  • History of any hemoglobinopathy that may affect determination of glycosylated hemoglobin.
  • History of infection with hepatitis B, hepatitis C, or human immunodeficiency virus.
  • History of a psychiatric disorder that will affect the subject's ability to participate in the study.
  • History of angioedema in association with use of angiotensin-converting enzyme inhibitors or angiotensin-II receptor inhibitors.
  • History of alcohol or substance abuse within the 2 years prior to Screening.
  • Receipt of any investigational drug within the 30 days prior to Screening or a history of receipt of an investigational antidiabetic drug within the 3 months prior to Screening.
  • Prior treatment in an investigational study of alogliptin.
  • Excluded Medications and Treatments:

    • Treatment with antidiabetic agents other than study drug or glyburide is not allowed within the 3 months prior to Screening and through the completion of the end-of-treatment/early termination procedures.
    • Treatment with weight-loss drugs, any investigational antidiabetics, Bosentan (used for the treatment of pulmonary hypertension), or oral or systemically injected glucocorticoids is not allowed from 3 months prior to randomization through the completion of the end-of- treatment/early termination procedures. Inhaled corticosteroids are allowed.
    • Subjects must not take any medications, including over-the-counter products, without first consulting with the investigator.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00286468

  Show 68 Study Locations
Sponsors and Collaborators
Takeda
Investigators
Study Director: VP Biological Sciences Takeda
  More Information

Publications:
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00286468     History of Changes
Other Study ID Numbers: SYR-322-SULF-007, 2005-004667-36, U1111-1113-8506
Study First Received: February 1, 2006
Results First Received: June 8, 2011
Last Updated: February 1, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Takeda:
Glucose Metabolism Disorder
Dysmetabolic Syndrome
Type II Diabetes
Diabetes Mellitus
Lipoatrophic
Dyslipidemia
Drug Therapy

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

ClinicalTrials.gov processed this record on April 16, 2014