Efficacy and Safety of Alogliptin in Subjects With Type 2 Diabetes

NCT ID: NCT00286455

Last Updated: 2012-02-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 329 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-02-28
• Study Completion Date: 2007-07-31

Brief Summary

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

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 efficacy of alogliptin in subjects with type 2 diabetes mellitus who are inadequately controlled and who have failed treatment with diet and exercise. 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).

Conditions

Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Alogliptin 12.5 mg QD

Group Type: EXPERIMENTAL

Alogliptin

Intervention Type: DRUG

Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.

Alogliptin 25 mg QD

Group Type: EXPERIMENTAL

Alogliptin

Intervention Type: DRUG

Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.

Placebo QD

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.

Interventions

Alogliptin

Alogliptin 12.5 mg, tablets, orally, once daily for up to 26 weeks.

Intervention Type: DRUG

Alogliptin

Alogliptin 25 mg, tablets, orally, once daily for up to 26 weeks.

Intervention Type: DRUG

Placebo

Alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.

Intervention Type: DRUG

Other Intervention Names

SYR110322; SYR-322; SYR110322; SYR-322

Eligibility Criteria

Inclusion Criteria

• Type 2 diabetes mellitus, experiencing inadequate glycemic control, and are receiving no current antidiabetic therapy. Subjects will qualify if both of the following conditions apply:

• Subject has failed treatment with diet and exercise for at least one month prior to Screening
• Subject has received less than 7 days of any antidiabetic therapy within the 3 months prior to Screening Diagnosis of type 2 diabetes must be based on current American Diabetes Association criteria.
• 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 per mL (greater than or equal to 0.26 nmol per L). (If this screening criterion is not met, the subject still qualifies if C-peptide greater than or equal to1.5 ng per mL (greater than or equal to 0.50 nmol per L) 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 to 180 mm Hg and diastolic pressure less than or equal to 110 mm Hg
• Hemoglobin greater than or equal to 12 g per dL (greater than or equal to 120 gm per L) for males and greater than or equal to 10 g per dL (greater than or equal to 100 gm per L) for females
• Alanine aminotransferase less than or equal to 3 times the upper limit of normal
• Serum creatinine less than or equal to 2.0 mg per dL (less than or equal to 17 micromol per 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 (confirmed by laboratory testing in females of childbearing potential) 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 than1000 μg per mg (greater than 113 mg per mol) 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 1 or cervical intraepithelial neoplasia 2 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

• Treatment with antidiabetic agents (other than study drug following enrollment in the study) is not allowed within the 3 months prior to Screening and through the completion of the end-of-treatment/early termination procedures. (Exception: if a subject has received other antidiabetic therapy for less than 7 days within the 3 months prior to Screening.)
• Treatment with weight-loss drugs, any investigational antidiabetics, 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 are not to take any medications, including over-the-counter products, without first consulting with the Study Doctor.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

VP Biological Sciences

Role: STUDY_DIRECTOR

Takeda

Locations

Birmingham, Alabama, United States

Peoria, Arizona, United States

Phoenix, Arizona, United States

Anaheim, California, United States

Artesia, California, United States

Fresno, California, United States

Lafayette, California, United States

Northridge, California, United States

Orange, California, United States

San Diego, California, United States

Walnut Creek, California, United States

Colorado Springs, Colorado, United States

Denver, Colorado, United States

Washington D.C., District of Columbia, United States

Cocoa Beach, Florida, United States

Kissimmee, Florida, United States

Longwood, Florida, United States

Ocala, Florida, United States

Ocoee, Florida, United States

Saint Cloud, Florida, United States

Honolulu, Hawaii, United States

Idaho Falls, Idaho, United States

Avon, Indiana, United States

Elkhart, Indiana, United States

Evansville, Indiana, United States

Baltimore, Maryland, United States

Sudbury, Massachusetts, United States

St Louis, Missouri, United States

Omaha, Nebraska, United States

Berlin, New Jersey, United States

Burlington, North Carolina, United States

Morehead City, North Carolina, United States

Pinehurst, North Carolina, United States

Winston-Salem, North Carolina, United States

Cincinnati, Ohio, United States

Tulsa, Oklahoma, United States

Lansdale, Pennsylvania, United States

West Grove, Pennsylvania, United States

Charleston, South Carolina, United States

Columbia, South Carolina, United States

Simpsonville, South Carolina, United States

Bristol, Tennessee, United States

Cookeville, Tennessee, United States

Milan, Tennessee, United States

Corpus Christi, Texas, United States

Dallas, Texas, United States

San Antonio, Texas, United States

Temple, Texas, United States

Texarkana, Texas, United States

Burlington, Vermont, United States

Multiple Cities, , Argentina

Multiple Cities, , Australia

Multiple Cities, , Brazil

Multiple Cities, , Chile

Multiple Cities, , Czechia

Multiple Cities, , Dominican Republic

Multiple Cities, , Germany

Multiple Cities, , Guatemala

Multiple Cities, , Hungary

Multiple Cities, , India

Multiple Cities, , Mexico

Multiple Cities, , Netherlands

Multiple Cities, , New Zealand

Multiple Cities, , Peru

Multiple Cities, , Poland

Multiple Cities, , South Africa

Multiple Cities, , United Kingdom

Countries

United States; Argentina; Australia; Brazil; Chile; Czechia; Dominican Republic; Germany; Guatemala; Hungary; India; Mexico; Netherlands; New Zealand; Peru; Poland; South Africa; United Kingdom

References

DeFronzo RA, Fleck PR, Wilson CA, Mekki Q; Alogliptin Study 010 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes and inadequate glycemic control: a randomized, double-blind, placebo-controlled study. Diabetes Care. 2008 Dec;31(12):2315-7. doi: 10.2337/dc08-1035. Epub 2008 Sep 22.

Reference Type: RESULT

PMID: 18809631 (View on PubMed)

Pratley RE, McCall T, Fleck PR, Wilson CA, Mekki Q. Alogliptin use in elderly people: a pooled analysis from phase 2 and 3 studies. J Am Geriatr Soc. 2009 Nov;57(11):2011-9. doi: 10.1111/j.1532-5415.2009.02484.x. Epub 2009 Sep 30.

Reference Type: RESULT

PMID: 19793357 (View on PubMed)

Other Identifiers

2005-004670-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1113-8462

Identifier Type: REGISTRY

Identifier Source: secondary_id

SYR-322-PLC-010

Identifier Type: -

Identifier Source: org_study_id