Study of Alogliptin Combined With Sulfonylurea in Subjects With Type 2 Diabetes Mellitus.

Takeda

Status and phase

Completed

Phase 3

Conditions

Diabetes Mellitus

Treatments

Drug: Alogliptin and glyburide

Drug: Glyburide

Study type

Interventional

Funder types

Industry

Identifiers

NCT00286468

U1111-1113-8506 (Registry Identifier)

SYR-322-SULF-007

2005-004667-36 (EudraCT Number)

Details and patient eligibility

About

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

Full 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 effectiveness of alogliptin in combination with a sulfonylurea in subjects who are inadequately controlled on a sulfonylurea alone. 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).

Enrollment

500 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Diagnosis of type 2 diabetes mellitus , currently treated with a sulfonylurea alone but experiencing inadequate glycemic control. Should have received the sulfonylurea monotherapy for at least the 3 months prior to Screening; has been on a stable sulfonylurea dose equivalent to at least 10 mg of glyburide (Exception: documented maximum tolerated dose equivalent to less than 10 mg but at least 5 mg glyburide) for at least 8 weeks.
No treatment with antidiabetic agents other than a sulfonylurea within the 3 months prior to Screening. (Exception: if a subject has received other antidiabetic therapy for less than 7 days within the 3 months prior to Screening.)
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/mL. (If this screening criterion is not met, the subject still qualifies if C-peptide is greater than or equal to 1.5 ng/mL 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 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 to 10 g per dL for females
Alanine aminotransferase less than or equal to 3 time the upper limit of normal.
Serum creatinine ≤2.0 mg/dL (≤17 micromol/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 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 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. (A 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 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 and Treatments:
- Treatment with antidiabetic agents other than study drug or glyburide is not allowed within the 3 months prior to Screening and through the completion of the end-of-treatment/early termination procedures.
- Treatment with weight-loss drugs, any investigational antidiabetics, Bosentan (used for the treatment of pulmonary hypertension), 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 must not take any medications, including over-the-counter products, without first consulting with the investigator.