Efficacy and Safety Study of Alogliptin Compared to Glipizide in Elderly Diabetics - Full Text View

Sponsored by:	Takeda Global Research & Development Center, Inc.
Information provided by:	Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier:	NCT00707993

Purpose

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.

Condition	Intervention	Phase
Diabetes Mellitus	Drug: SYR-322 Drug: Glipizide	Phase III

MedlinePlus related topics: Diabetes

Drug Information available for: Glipizide Dextrose Alogliptin

U.S. FDA Resources

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

Further study details as provided by Takeda Global Research & Development Center, Inc.:

Primary Outcome Measures:

Change from baseline in Glycosylated Hemoglobin [ Time Frame: Week 52 or Final Visit ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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

Estimated Enrollment:	470
Study Start Date:	June 2008
Estimated Study Completion Date:	June 2010
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: SYR-322 SYR-322 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.
2: Active Comparator	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.

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.

Eligibility

Ages Eligible for Study:	65 Years to 90 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00707993

Contacts

Contact: Takeda Study Registration Call Center

800-778-2860

medicalinformation@tpna.com

Show 29 Study Locations

Sponsors and Collaborators

Takeda Global Research & Development Center, Inc.

Investigators

Study Director:

VP Biological Sciences

Takeda Global Research & Development Center, Inc.

More Information

Responsible Party:	Takeda Global Research & Development Center, Inc. ( Sr. VP, Clinical Science )
Study ID Numbers:	SYR-322_303, 2008-000-959-10
Study First Received:	June 27, 2008
Last Updated:	December 18, 2008
ClinicalTrials.gov Identifier:	NCT00707993
Health Authority:	United States: Food and Drug Administration

Keywords provided by Takeda Global Research & Development Center, Inc.:

Glucose Metabolism Disorder
Dysmetabolic Syndrome
Type II Diabetes
Diabetes Mellitus

Lipoatrophic
Dyslipidemia
Drug Therapy

Study placed in the following topic categories:

Glipizide
Metabolic Diseases
Diabetes Mellitus, Type 2
Diabetes Mellitus
Endocrine System Diseases

Endocrinopathy
Metabolic disorder
Glucose Metabolism Disorders
Dyslipidemias

Additional relevant MeSH terms:

Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009