Efficacy and Safety Study of Alogliptin and Insulin in the Treatment of Type 2 Diabetes.

NCT ID: NCT00286429

Last Updated: 2012-02-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 390 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-02-28
• Study Completion Date: 2007-05-31

Brief Summary

The purpose of this study is to determine the efficacy and safety of alogliptin, once daily (QD), taken in combination with insulin for the treatment of 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 alogliptin (SYR-322) for 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 combination with insulin in subjects who are inadequately controlled on insulin alone (with or without metformin). 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

Insulin

Group Type: PLACEBO_COMPARATOR

Insulin

Intervention Type: DRUG

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

Alogliptin 12.5 mg QD

Group Type: EXPERIMENTAL

Alogliptin and insulin

Intervention Type: DRUG

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

Alogliptin 25 mg QD

Group Type: EXPERIMENTAL

Alogliptin and insulin

Intervention Type: DRUG

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

Interventions

Alogliptin and insulin

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

Intervention Type: DRUG

Alogliptin and insulin

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

Intervention Type: DRUG

Insulin

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

Intervention Type: DRUG

Other Intervention Names

alogliptin; SYR110322; alogliptin; SYR110322

Eligibility Criteria

Inclusion Criteria

• Diagnosis of type 2 diabetes mellitus and currently treated with insulin alone (with or without metformin), and is inadequately controlled. Metformin dose must be stable for at least 8 weeks prior to Randomization.
• No treatment with antidiabetic agents other than insulin and metformin within the 8 weeks prior to Randomization.
• 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. (If this screening criterion is not met, the subject still qualifies if C-peptide greater than or equal to 1.5 ng per mL after a challenge test).
• Glycosylated hemoglobin concentration greater than or equal to 8.0% at Screening.
• Using a stable dose of insulin of at least 15 units but not more than 100 units per day for at least 8 weeks prior to Randomization. A dose of insulin that varies by up to 15% of the mean will be considered as stable.
• 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 to180 mm Hg and diastolic pressure less than or equal to 110 mm Hg
• Hemoglobin greater than or equal to 12 g per dL for males and greater than or equal to10 g per dL 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.
• 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 own blood glucose concentrations with a home glucose monitor
• No major illness or debility that in the investigator's opinion prohibits the individual from completing the study
• Able and willing to provide written informed consent

Exclusion Criteria

• Urine albumin to creatinine ratio of greater than 1000 μg per mg 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. (History of treated cervical intraepithelial neoplasia I or cervical intraepithelial neoplasia II 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 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 insulin and metformin is not allowed within the 8 weeks prior to Randomization and through the completion of the end-of treatment or early termination procedures. (Exception: if 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 or early termination procedures. Inhaled corticosteroids are allowed.
• Must not take any medications, including over-the-counter products, without first consulting with the investigator.

• 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

Phoenix, Arizona, United States

Anaheim, California, United States

Artesia, California, United States

Fresno, California, United States

Mission Viejo, California, United States

Northridge, California, United States

Orange, California, United States

San Diego, California, United States

Tustin, California, United States

Walnut Creek, California, United States

Denver, Colorado, United States

Cocoa Beach, Florida, United States

Longwood, Florida, United States

New Port Richey, Florida, United States

Ocala, Florida, United States

Saint Cloud, Florida, United States

Tampa, Florida, United States

Lawrenceville, Georgia, United States

Honolulu, Hawaii, United States

Avon, Indiana, United States

Evansville, Indiana, United States

Lafayette, Indiana, United States

St Louis, Missouri, United States

Omaha, Nebraska, United States

Berlin, New Jersey, United States

Burlington, North Carolina, United States

Charlotte, North Carolina, United States

Hickory, 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

Medford, Oregon, United States

Lansdale, Pennsylvania, United States

Charleston, South Carolina, United States

Columbia, South Carolina, United States

Simpsonville, South Carolina, United States

Cookeville, 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, , 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

Countries

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

References

Rosenstock J, Rendell MS, Gross JL, Fleck PR, Wilson CA, Mekki Q. Alogliptin added to insulin therapy in patients with type 2 diabetes reduces HbA(1C) without causing weight gain or increased hypoglycaemia. Diabetes Obes Metab. 2009 Dec;11(12):1145-52. doi: 10.1111/j.1463-1326.2009.01124.x. Epub 2009 Sep 16.

Reference Type: RESULT

PMID: 19758359 (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

2005-004671-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1113-8369

Identifier Type: REGISTRY

Identifier Source: secondary_id

SYR-322-INS-011

Identifier Type: -

Identifier Source: org_study_id