Efficacy and Safety Study of Alogliptin Compared to Glipizide in Elderly Diabetics

Condition(s) targeted: Diabetes Mellitus

Intervention: SYR-322 (Drug); Glipizide (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Takeda Global Research & Development Center, Inc.

Official(s) and/or principal investigator(s):
VP Biological Sciences, Study Director, Affiliation: Takeda Global Research & Development Center, Inc.

Overall contact:
Takeda Study Registration Call Center, Phone: 800-778-2860, Email: medicalinformation@tpna.com

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.

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

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Active Control, Single Group Assignment, Safety/Efficacy Study

Primary outcome: Change from baseline in Glycosylated Hemoglobin

Secondary outcome:

Glycosylated Hemoglobin

Incidence of hypoglycemia

Incidence of marked hyperglycemia (fasting plasma glucose ≥200 mg/dL).

Fasting plasma glucose

2-hour postprandial glucose

Proinsulin

Insulin

Proinsulin/insulin ratio

Homeostasis model assessment-B-cell function

Body weight

Serum lipids

High sensitivity C-reactive protein testing

Clinical response endpoint incidence of glycosylated hemoglobin measurement less than or equal to 6.5%.

Clinical response endpoint incidence of glycosylated hemoglobin measurement less than or equal to 7.0%.

Clinical response endpoint incidence of glycosylated hemoglobin decrease from baseline greater than or equal to 0.5%.

Clinical response endpoint incidence of glycosylated hemoglobin decrease from baseline greater than or equal to 1.0%.

Clinical response endpoint incidence of glycosylated hemoglobin decrease from baseline greater than or equal to 1.5%.

Clinical response endpoint incidence of glycosylated hemoglobin decrease from baseline greater than or equal to 2.0%.

Quality of Life scale scores and Patient Reported Outcome measures

Incidence of hyperglycemic rescue.

Detailed description: 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.

Minimum age: 65 Years. Maximum age: 90 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- The subject is male or female, between the ages of 65 and 90, inclusive, with a

diagnosis of type 2 diabetes mellitus who has 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. However, PRN (as needed) use of prescription or over-the-counter medications is allowed at the discretion of the investigator.

- Female subject of childbearing potential who is sexually active agrees to use adequate

contraception from screening throughout the duration of the study, and can neither pregnant nor lactating.

- 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.

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 (less than or equal to 120 gm/L) for males or

less than or equal to 10 g/dL (less than or equal to 100 gm/L) 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. (A history of treated CIN I or CIN II [cervical intraepithelial neoplasia] is allowed.)

- 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.

Currently treated subjects who are stable at Class I or II are candidates for the study (see Appendix E).

- 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 HIV.

- 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.

- Subject has donated more than 400 mL of blood within the 90 days preceding their

participation in the study.

- Subjects who have hypersensitivity or have had an anaphylactic reaction(s) to any

DPP-4 inhibitor drug.

Takeda Study Registration Call Center, Phone: 800-778-2860, Email: medicalinformation@tpna.com

Alexander City, Alabama, United States; Recruiting

Foothill Ranch, California, United States; Recruiting

Huntington Park, California, United States; Recruiting

Long Beach, California, United States; Recruiting

Los Angeles, California, United States; Recruiting

Redlands, California, United States; Recruiting

Prospect, Connecticut, United States; Recruiting

Bradenton, Florida, United States; Recruiting

Fort Myers, Florida, United States; Recruiting

Miami, Florida, United States; Recruiting

Ormond Beach, Florida, United States; Recruiting

Roswell, Georgia, United States; Recruiting

South Bend, Indiana, United States; Recruiting

Salisbury, Maryland, United States; Recruiting

Clarkston, Michigan, United States; Recruiting

Omaha, Nebraska, United States; Recruiting

Hamilton, New Jersey, United States; Recruiting

Beachwood, Ohio, United States; Recruiting

Westlake, Ohio, United States; Recruiting

Zanesville, Ohio, United States; Recruiting

Bensalem, Pennsylvania, United States; Recruiting

Aiken, South Carolina, United States; Recruiting

Greenville, South Carolina, United States; Recruiting

Taylors, South Carolina, United States; Recruiting

Corpus Christi, Texas, United States; Recruiting

Pasadena, Texas, United States; Recruiting

San Antonio, Texas, United States; Recruiting

Tomball, Texas, United States; Recruiting

Salt Lake City, Utah, United States; Recruiting

Starting date: June 2008
Ending date: June 2010
Last updated: December 18, 2008