Official Title: “A Multicenter, Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Alogliptin Compared to Glipizide in Elderly Subjects With Type 2 Diabetes”

The purpose of this study is to evaluate the efficacy and safety of alogliptin compared to glipizide in elderly diabetic patients who have not received treatment or are on a single oral medication.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: June 2010

Type 2 diabetes is among the most common chronic condition in adults 65 years of age or older. A recent National Health and Nutrition Examination Survey reported that more than 20% of adults aged 65 years or older have diabetes. These individuals are often under-treated with respect to glucose-lowering medications, and their care is complicated by the extent of their clinical and functional status. Age-related changes in physiology, diabetes-associated illnesses and other illnesses (such as renal, cardiac, and hepatic insufficiency), as well as use of multiple medications make standard oral anti-hyperglycemic therapy and insulin use problematic. In addition, hypoglycemia is more common and severe in older rather than younger patients taking oral antidiabetic drugs which can precipitate serious events such as falls and hip fractures. While avoidance of hypoglycemia is paramount in elderly diabetic patients, many commonly used medications are associated with a substantial risk for hypoglycemia. New classes of drug which avoid such complications in the elderly population are of increasing interest as this population continues to expand.

Takeda is developing SYR-322 (alogliptin) for the improvement of glycemic control in patients with type 2 diabetes mellitus. SYR-322 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.

This study will compare the effectiveness and safety of SYR-322 with that of glipizide (a commonly used diabetes medication) in adults who are 65 to 90 years of age with Type 2 diabetes. Individuals who participate in this study will either have failed diet and exercise therapy alone during the 2 months before Screening, or will have been receiving a single oral antidiabetic medication without obtaining good blood glucose (sugar) control.

Each participant will be required to commit to screening visits. Study participation is anticipated to be up to 59 weeks.

Intervention(s) in this Clinical Trial

• Drug: SYR-322
  • SYR-322 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.
• Drug: Glipizide
  • SYR-322 placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Active Comparator: 2

Primary Measures

• Change from baseline in Glycosylated Hemoglobin
  • Time Frame: Week 52
    Safety Issue?: No

Secondary Measures

• Glycosylated Hemoglobin
  • Time Frame: Weeks 4, 8, 12, 16, 20, 26, 34, and 42
    Safety Issue?: No
• Incidence of hypoglycemia
  • Time Frame: At Each Occurrence
    Safety Issue?: No
• Incidence of marked hyperglycemia (fasting plasma glucose ≥200 mg/dL).
  • Time Frame: At Each Occurrence
    Safety Issue?: No
• Fasting plasma glucose
  • Time Frame: Weeks 2, 4, 8, 12, 16, 20, 26, 34, 42 and 52
    Safety Issue?: No
• 2-hour postprandial glucose
  • Time Frame: Weeks 26 and 52
    Safety Issue?: No
• Proinsulin
  • Time Frame: Weeks 12, 26, 42 and 52
    Safety Issue?: No
• Insulin
  • Time Frame: Weeks 12, 26, 42 and 52
    Safety Issue?: No
• Proinsulin/insulin ratio
  • Time Frame: Weeks 12, 26, 42 and 52
    Safety Issue?: No
• Homeostasis model assessment-B-cell function
  • Time Frame: Weeks 12, 26, 42 and 52
    Safety Issue?: No
• Body weight
  • Time Frame: Weeks 8, 12, 26, 42 and 52
    Safety Issue?: No
• Serum lipids
  • Time Frame: Weeks 8, 12, 26, 42 and 52
    Safety Issue?: No
• High sensitivity C-reactive protein testing
  • Time Frame: Weeks 12, 26, 42 and 52
    Safety Issue?: No
• Clinical response endpoint incidence of glycosylated hemoglobin measurement less than or equal to 6.5%.
  • Time Frame: Week 52
    Safety Issue?: No
• Clinical response endpoint incidence of glycosylated hemoglobin measurement less than or equal to 7.0%.
  • Time Frame: Week 52
    Safety Issue?: No
• Clinical response endpoint incidence of glycosylated hemoglobin decrease from baseline greater than or equal to 0.5%.
  • Time Frame: Week 52
    Safety Issue?: No
• Clinical response endpoint incidence of glycosylated hemoglobin decrease from baseline greater than or equal to 1.0%.
  • Time Frame: Week 52
    Safety Issue?: No
• Clinical response endpoint incidence of glycosylated hemoglobin decrease from baseline greater than or equal to 1.5%.
  • Time Frame: Week 52
    Safety Issue?: No
• Clinical response endpoint incidence of glycosylated hemoglobin decrease from baseline greater than or equal to 2.0%.
  • Time Frame: Week 52
    Safety Issue?: No
• Quality of Life scale scores and Patient Reported Outcome measures
  • Time Frame: Week 52
    Safety Issue?: No
• Incidence of hyperglycemic rescue.
  • Time Frame: At Each Occurrence
    Safety Issue?: No

Inclusion Criteria:

• Has a diagnosis of type 2 diabetes mellitus with either:
• Failed diet and exercise therapy alone as demonstrated by inadequate glycemic control while receiving no antidiabetic treatment within the two months prior to Screening, or
• Failed treatment with oral monotherapy alone (may include treatment with two or more antidiabetic agents if for less than 7 days) as demonstrated by inadequate glycemic control within the two months prior to Screening.
• Body mass index greater than or equal to 23 kg/m2 and less than or equal to 45 kg/m2.
• If regularly using other, non-excluded medications, must be on a stable dose for at least the 4 weeks prior to Screening.
• Females of childbearing potential who are sexually active must agree to use a medically accepted means of contraception, and can neither be pregnant nor lactating from Screening throughout the duration of 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 participant from completing the study.

Exclusion Criteria:

• Systolic blood pressure greater than or equal to 160 mm Hg and/or diastolic pressure greater than or equal to 100 mm Hg.
• Hemoglobin less than or equal to 12 g/dL for males or less than or equal to 10 g/dL for females.
• Alanine aminotransferase greater than or equal to 3 times the upper limit of normal.
• Calculated creatinine clearance less than or equal to 50 mL/min.
• Thyroid-stimulating hormone level outside of the normal range.
• 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.
• History of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening.
• History of treated diabetic gastroparesis, gastric banding, or gastric bypass surgery.
• New York Heart Association Class III or IV heart failure regardless of therapy.
• 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 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.
• History of treatment with any weight-loss drugs or oral or systemically injected glucocorticoids within the 3 months prior to Screening.
• Receipt of any investigational drug within the 30 days prior to Screening.
• Prior treatment in an investigational study of alogliptin.
• Clinically significant medical abnormality or disease or clinically significant abnormal findings at Screening (other than type 2 diabetes) that, in the opinion of the investigator, should exclude the subject from the study.
• Has donated more than 400 mL of blood within the 90 days preceding their participation in the study.
• Has hypersensitivity or has had an anaphylactic reaction(s) to any DPP-4 inhibitor drug.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 65 Years

Maximum Age for this Clinical Trial: 90 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Takeda Global Research & Development Center, Inc.

Overall Clinical Trial Officials and Contacts

VP Biological Sciences Study Director Takeda Global Research & Development Center, Inc.  

Overall Contact: Takeda Study Registration Call Center 800-778-2860 medicalinformation@tpna.com

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00707993

Study ID Number: SYR-322_303

ClinicalTrials.gov Identifier: NCT00707993

Health Authority: Germany: Federal Institute for Drugs and Medical Devices