Efficacy and Safety of Alogliptin Compared to Glipizide in Elderly Diabetics

Condition(s) targeted: Diabetes Mellitus

Intervention: Alogliptin (Drug); Glipizide (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Takeda

Official(s) and/or principal investigator(s):
VP Biological Sciences, Study Director, Affiliation: Takeda

The purpose of this study is to evaluate the efficacy and safety of alogliptin, once daily (QD), 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: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Change From Baseline in Glycosylated Hemoglobin at Week 52.

Secondary outcome:

Change From Baseline in Glycosylated Hemoglobin

Incidence of Hypoglycemia

Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL).

Incidence of Hyperglycemic Rescue

Change From Baseline in Fasting Plasma Glucose

Change From Baseline in 2-hour Postprandial Glucose

Change From Baseline in Fasting Proinsulin

Change From Baseline in Insulin

Change From Baseline in Proinsulin/Insulin Ratio

Homeostasis Model Assessment of Beta Cell Function

Change From Baseline in Body Weight

Change From Baseline in Serum Lipids (Total Cholesterol)

Change From Baseline in Serum Lipids (High-Density Lipoprotein Cholesterol)

Change From Baseline in Serum Lipids (Low-Density Lipoprotein Cholesterol)

Change From Baseline in Serum Lipids (Triglycerides)

Change From Baseline in High Sensitivity C-reactive Protein

Incidence of Subjects Achieving Glycosylated Hemoglobin <=7%

Incidence of Glycosylated Hemoglobin Decrease From Baseline.

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. 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. This study will compare the effectiveness and safety of alogliptin 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:

- 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 participant'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 participant 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.

Budapest, Hungary

Miskoic, Hungary

Nyiregyhaza, Hungary

Ashkelon, Israel

Haifa, Israel

Holon, Israel

Nahariya, Israel

Rishon Le-Zion, Israel

Zefat, Israel

Aguascalientes, Mexico

Durango, Mexico

Guadalajara, Mexico

Mexico DF, Mexico

Nezahualcoyotl, Mexico

Arequipa, Peru

Lima, Peru

Piura, Peru

Gdansk, Poland

Krakow, Poland

Warszawa, Poland

Baia Mare, Romania

Brasov, Romania

Bucharest, Romania

Galati, Romania

Satu Mare, Romania

Arkhangelsk, Russian Federation

Irkutsk, Russian Federation

Smolensk, Russian Federation

Cape Town, South Africa

Centurion, South Africa

Durban, South Africa

Johannesburg, South Africa

Port Elizabeth, South Africa

Pretoria, South Africa

Donetsk, Ukraine

Kharkiv, Ukraine

Alexander City, Alabama, United States

Foothill Ranch, California, United States

Huntington Park, California, United States

Long Beach, California, United States

Los Angeles, California, United States

Redlands, California, United States

Saltillo, Coahuila, Mexico

Prospect, Connecticut, United States

Bradenton, Florida, United States

Fort Myers, Florida, United States

Miami, Florida, United States

Ormond Beach, Florida, United States

Winter Park, Florida, United States

Roswell, Georgia, United States

Karnal, Haryana, India

Pachuca, Hidalgo, Mexico

Aurora, Illinois, United States

LaPorte, Indiana, United States

South Bend, Indiana, United States

Bangalore, Karnataka, India

Belgaum, Karnataka, India

Mumbai, Maharashrta, India

Salisbury, Maryland, United States

Clarkston, Michigan, United States

Morelia, Michoacan, Mexico

Omaha, Nebraska, United States

Hamilton, New Jersey, United States

Albuquerque, New Mexico, United States

Monterrey, Nuevo Leon, Mexico

Beachwood, Ohio, United States

Westlake, Ohio, United States

Zanesville, Ohio, United States

Bensalem, Pennsylvania, United States

Aiken, South Carolina, United States

Greenville, South Carolina, United States

Greer, South Carolina, United States

Taylors, South Carolina, United States

Corpus Christi, Texas, United States

Dallas, Texas, United States

Pasadena, Texas, United States

San Antonio, Texas, United States

Tomball, Texas, United States

Ogden, Utah, United States

Salt Lake City, Utah, United States

Starting date: June 2008
Last updated: May 22, 2013