Efficacy and Safety of Alogliptin Plus Metformin in Subjects With Type 2 Diabetes

Official Title: “A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of Alogliptin Plus Metformin, Alogliptin Alone, or Metformin Alone in Subjects With Type 2 Diabetes”

The purpose of this study is to evaluate the safety and effectiveness of alogliptin combined with metformin, once daily (QD) or twice daily (BID), in participants with Type 2 Diabetes.

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.

Metformin is the usual choice of first-line therapy for type 2 diabetes. Metformin targets insulin resistance in type 2 diabetes by inhibiting hepatic glucose production and stimulating glucose uptake in skeletal muscle and adipose tissue, which results in a long-term glucose-lowering effect.

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.

Based on the potential, complimentary mechanisms of action of alogliptin and metformin, this study will compare the safety and efficacy of alogliptin and metformin (SYR-322MET) on improving glycemic control in patients with type 2 diabetes mellitus who are inadequately controlled by diet adjustment and exercise alone.

Participants taking part in this study will receive dietary and exercise coaching, and will monitor their own blood glucose concentrations with a home glucose monitor. Participants will also be required to maintain a hypoglycemic diary throughout the course of the study.

Participation in this study is expected to last up to 34 weeks.

Intervention(s) in this Clinical Trial

• Drug: Metformin
  • Alogliptin placebo-matching tablets, orally, twice daily and Metformin 500 mg capsules, orally, twice daily for up to 26 weeks.
• Drug: Metformin
  • Alogliptin placebo-matching tablets, orally, twice daily and Metformin 1000mg capsules, orally, twice daily for up to 26 weeks.
• Drug: Alogliptin
  • Alogliptin 12.5 mg, tablets, orally, twice daily and Metformin placebo-matching capsules, orally, twice daily for up to 26 weeks.
• Drug: Alogliptin
  • Alogliptin 25 mg, tablets, orally, once daily and Metformin placebo-matching capsules, orally, twice daily for up to 26 weeks.
• Drug: Alogliptin and Metformin
  • Alogliptin 12.5mg, tablets, orally, twice daily and Metformin 500 mg, capsules, orally, twice daily for up to 26 weeks.
• Drug: Alogliptin and Metformin
  • Alogliptin 12.5mg, tablets, orally, twice daily and Metformin 1000 mg, capsules, orally, twice daily for up to 26 weeks.
• Drug: Placebo
  • Alogliptin placebo-matching tablets, orally, twice daily and Metformin placebo-matching capsules, orally, twice daily for up to 26 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Alogliptin 12 mg BID
• Experimental: Alogliptin 25 mg QD
• Experimental: Alogliptin 12.5 mg BID and Metformin 500 mg BID
• Experimental: Alogliptin 12.5 mg BID and Metformin 1000 mg BID
• Active Comparator: Metformin 500 mg BID
• Active Comparator: Metformin 1000 mg BID
• Placebo Comparator: Placebo

Primary Measures

• Change from Baseline in Glycosylated Hemoglobin at Week 26.
  • Time Frame: Baseline and Week 26.
    Safety Issue?: No

Secondary Measures

• Change from Baseline in Glycosylated Hemoglobin at Week 4.
  • Time Frame: Baseline and Week 4.
    Safety Issue?: No
• Change from Baseline in Glycosylated Hemoglobin at Week 8.
  • Time Frame: Baseline and Week 8.
    Safety Issue?: No
• Change from Baseline in Glycosylated Hemoglobin at Week 12.
  • Time Frame: Baseline and Week 12
    Safety Issue?: No
• Change from Baseline in Glycosylated Hemoglobin at Week 16.
  • Time Frame: Baseline and Week 16.
    Safety Issue?: No
• Change from Baseline in Glycosylated Hemoglobin at Week 20.
  • Time Frame: Baseline and Week 20.
    Safety Issue?: No
• Change from Baseline in Fasting Plasma Glucose at Week 1.
  • Time Frame: Baseline and Week 1.
    Safety Issue?: No
• Change from Baseline in Fasting Plasma Glucose at Week 2.
  • Time Frame: Baseline and Week 2.
    Safety Issue?: No
• Change from Baseline in Fasting Plasma Glucose at Week 4.
  • Time Frame: Baseline and Week 4.
    Safety Issue?: No
• Change from Baseline in Fasting Plasma Glucose at Week 8.
  • Time Frame: Baseline and Week 8.
    Safety Issue?: No
• Change from Baseline in Fasting Plasma Glucose at Week 12.
  • Time Frame: Baseline and Week 12.
    Safety Issue?: No
• Change from Baseline in Fasting Plasma Glucose at Week 16.
  • Time Frame: Baseline and Week 16.
    Safety Issue?: No
• Change from Baseline in Fasting Plasma Glucose at Week 20.
  • Time Frame: Baseline and Week 20.
    Safety Issue?: No
• Change from Baseline in Fasting Plasma Glucose at Week 26.
  • Time Frame: Baseline and Week 26.
    Safety Issue?: No

Inclusion Criteria:

• Has historical diagnosis of Type 2 Diabetes Mellitus.
• Has been treated with diet and exercise for at least 2 months prior to Screening, and has a Glycosylated Hemoglobin concentration between 7.5% and 10.0%, inclusive at
• Screening.
• Has received less than 7 days of any antidiabetic medication within 2 months prior to Screening.
• Body mass index greater than or equal to 23 kg/m2 and less than or equal to 45 kg/m2 (except for Asian or Asian-descendant subjects for whom the range is between 20 and 35 kg/ m2, inclusive).
• Fasting C-peptide concentration greater than or equal to 0.8 ng/mL.
• Regularly using other, non-excluded, medications must be on a stable dose for at least the 4 weeks prior to Screening.
• Females of childbearing potential and males who are sexually active agree to routinely use adequate contraception from Screening throughout the duration of the study.
• Is able and willing to monitor their own blood glucose concentrations with a home glucose monitor and complete subject diaries.

Exclusion Criteria:

• Hemoglobin less than 12 g/dL for males and less than 10 g/dL for females at Screening Visit.
• Has a history of any hemoglobinopathy that may affect determination of Glycosylated
• Hemoglobin.
• Has a history of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening.
• Has a history of treatment for diabetic gastric paresis, gastric banding, or gastric bypass surgery.
• Has a history of diabetic ketoacidosis or hyperosmolar non-ketotic coma.
• Has systolic blood pressure greater than or equal to150 mmHg and /or diastolic pressure greater than or equal to 90 mmHg at Screening visit.
• Has New York Heart Association Class III to IV heart failure.
• Has a history of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within the 90 days prior to Screening.
• Has Alanine aminotransferase greater than 3 times the upper limit of normal at
• Screening.
• Has a history of alcohol or substance abuse with the 2 years prior to Screening.
• Serum creatinine greater than or equal to 1.5 mg/dL for males and greater than or equal to1.4 mg/dL for females.
• Has 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.
• Has a history of infection with human immunodeficiency virus, hepatitis B virus or hepatitis C virus.
• Has any major illness or debility that in the investigator's opinion prohibits the subject from completing the study.
• Has received any investigational drug within the 90 days prior to Screening.
• Has a history of hypersensitivity or allergy to alogliptin, other DPP-4 inhibitors, metformin or related compounds.
• Has used oral or systematically injected glucocorticoids or weight loss drugs prior to 2 months to screening.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Takeda Global Research & Development Center, Inc. Industry

Overall Clinical Trial Officials and Contacts

Vice President, Clinical Science Study Director Takeda Global Research & Development Center, Inc.  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01023581

Study ID Number: SYR-322MET_302

ClinicalTrials.gov Identifier: NCT01023581

Health Authority: Guatemala: Ministry of Public Health and Social Assistance