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

Takeda

Status and phase

Completed

Phase 3

Conditions

Diabetes Mellitus

Treatments

Drug: Insulin

Drug: Alogliptin and insulin

Study type

Interventional

Funder types

Industry

Identifiers

NCT00286429

2005-004671-38 (EudraCT Number)

SYR-322-INS-011

U1111-1113-8369 (Registry Identifier)

Details and patient eligibility

About

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.

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 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).

Enrollment

390 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 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.