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Efficacy and Safety of Alogliptin Plus Metformin in Patients With Type 2 Diabetes (AM7D)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01023581
First received: December 1, 2009
Last updated: February 17, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Alogliptin
Drug: Metformin
Drug: Alogliptin Placebo
Drug: Metformin Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 [ Time Frame: Baseline and Week 26. ] [ Designated as safety issue: No ]
    The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound).


Secondary Outcome Measures:
  • Change From Baseline in HbA1c Over Time [ Time Frame: Baseline and Weeks 4, 8, 12, 16, and 20. ] [ Designated as safety issue: No ]

    The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) was assessed at Weeks 4, 8, 12, 16 and 20.

    Least squares means are from an analysis of covariance (ANCOVA) model with treatment and geographic region as fixed effects, and baseline HbA1c as a covariate.


  • Change From Baseline in Fasting Plasma Glucose Over Time [ Time Frame: Baseline and Weeks 1, 2, 4, 8, 12, 16, 20 and 26. ] [ Designated as safety issue: No ]
    The change from Baseline in fasting plasma glucose was assessed at Weeks 1, 2, 4, 8, 12, 16, 20 and 26. Least Squares Means were from an ANCOVA model with treatment and geographic region as fixed effects, and baseline fasting plasma glucose as a covariate.


Enrollment: 784
Study Start Date: November 2009
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Alogliptin placebo-matching tablets, orally, twice daily and Metformin placebo-matching capsules, orally, twice daily for up to 26 weeks.
Drug: Alogliptin Placebo
Alogliptin placebo-matching tablets.
Drug: Metformin Placebo
Metformin placebo-matching capsules.
Experimental: Alogliptin 25 QD
Alogliptin 25 mg, tablets, orally, once daily (QD) and Metformin placebo-matching capsules, orally, twice daily for up to 26 weeks.
Drug: Alogliptin
Alogliptin tablets.
Other Name: SYR-322
Drug: Metformin Placebo
Metformin placebo-matching capsules.
Experimental: Alogliptin 12.5 BID
Alogliptin 12.5 mg, tablets, orally, twice daily (BID) and Metformin placebo-matching capsules, orally, twice daily for up to 26 weeks.
Drug: Alogliptin
Alogliptin tablets.
Other Name: SYR-322
Drug: Metformin Placebo
Metformin placebo-matching capsules.
Active Comparator: Metformin 500 BID
Alogliptin placebo-matching tablets, orally, twice daily and Metformin 500 mg capsules, orally, twice daily for up to 26 weeks.
Drug: Metformin
Metformin capsules
Other Names:
  • Glucophage
  • Glucophage XR
  • Riomet
  • Fortamet
  • Glumetza
  • Obimet
  • Dianben
  • Diabex
  • Diaformin
Drug: Alogliptin Placebo
Alogliptin placebo-matching tablets.
Active Comparator: Metformin 1000 BID
Alogliptin placebo-matching tablets, orally, twice daily and Metformin 1000 mg capsules, orally, twice daily for up to 26 weeks.
Drug: Metformin
Metformin capsules
Other Names:
  • Glucophage
  • Glucophage XR
  • Riomet
  • Fortamet
  • Glumetza
  • Obimet
  • Dianben
  • Diabex
  • Diaformin
Drug: Alogliptin Placebo
Alogliptin placebo-matching tablets.
Experimental: Alogliptin 12.5 BID + Metformin 500 BID
Alogliptin 12.5mg, tablets, orally, twice daily and Metformin 500 mg, capsules, orally, twice daily for up to 26 weeks.
Drug: Alogliptin
Alogliptin tablets.
Other Name: SYR-322
Drug: Metformin
Metformin capsules
Other Names:
  • Glucophage
  • Glucophage XR
  • Riomet
  • Fortamet
  • Glumetza
  • Obimet
  • Dianben
  • Diabex
  • Diaformin
Experimental: Alogliptin 12.5 BID + Metformin 1000 BID
Alogliptin 12.5 mg, tablets, orally, twice daily and Metformin 1000 mg, capsules, orally, twice daily for up to 26 weeks.
Drug: Alogliptin
Alogliptin tablets.
Other Name: SYR-322
Drug: Metformin
Metformin capsules
Other Names:
  • Glucophage
  • Glucophage XR
  • Riomet
  • Fortamet
  • Glumetza
  • Obimet
  • Dianben
  • Diabex
  • Diaformin

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.

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-4 enzyme is thought to be primarily responsible for the in vivo degradation of 2 peptide hormones released in response to nutrient ingestion, namely glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. Both peptides exert important effects on islet beta cells to stimulate glucose-dependent insulin secretion as well as regulating beta cell proliferation and cytoprotection. Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits gastric emptying, glucagon secretion, and food intake. Glucose-dependent insulinotropic peptide has been shown to enhance insulin secretion by direct interaction with a glucose-dependent insulinotropic peptide -specific receptor on islet beta cells. The glucose-lowering actions of glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, are preserved in patients with type 2 diabetes mellitus. 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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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/m^2 and less than or equal to 45 kg/m^2 (except for Asian or Asian-descendant subjects for whom the range is between 20 and 35 kg/ m^2, 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.
  • Able and willing to monitor their own blood glucose concentrations with a home glucose monitor and complete patient 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 to 150 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 to 1.4 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01023581

  Show 201 Study Locations
Sponsors and Collaborators
Takeda
Investigators
Study Director: Vice President, Clinical Science Takeda
  More Information

No publications provided by Takeda

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01023581     History of Changes
Other Study ID Numbers: SYR-322MET_302, 2009-012652-24, U1111-1112-1912, DOH-27-0910-3155, CTRI/2010/091/000253
Study First Received: December 1, 2009
Results First Received: February 17, 2013
Last Updated: February 17, 2013
Health Authority: Guatemala: Ministry of Public Health and Social Assistance
Mexico: Ethics Committee
Mexico: Federal Commission for Protection Against Health Risks
Mexico: Federal Commission for Sanitary Risks Protection
Mexico: Ministry of Health
Mexico: National Council of Science and Technology
Mexico: National Institute of Public Health, Health Secretariat
Czech Republic: Ethics Committee
Czech Republic: State Institute for Drug Control
Hungary: National Institute of Pharmacy
Israel: The Israel National Institute for Health Policy Research and Health Services Research
Israel: Ethics Commission
Israel: Israeli Health Ministry Pharmaceutical Administration
Israel: Ministry of Health
Lithuania: Bioethics Committee
Lithuania: State Medicine Control Agency - Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Poland: Ministry of Health
Poland: Ministry of Science and Higher Education
Romania: Ministry of Public Health
Romania: National Medicines Agency
Romania: State Institute for Drug Control
Russia: Ethics Committee
Russia: Ministry of Health of the Russian Federation
Russia: Pharmacological Committee, Ministry of Health
South Africa: Department of Health
South Africa: Medicines Control Council
South Africa: National Health Research Ethics Council
Ukraine: Ministry of Health
Ukraine: State Pharmacological Center - Ministry of Health
United States: Food and Drug Administration

Keywords provided by Takeda:
Type 2 Diabetes mellitus
Non-insulin dependent diabetes mellitus
Drug Therapy
Hypoglycemia,
Hyperglycemia

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Alogliptin
Metformin
Dipeptidyl-Peptidase IV Inhibitors
Enzyme Inhibitors
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Incretins
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors

ClinicalTrials.gov processed this record on November 25, 2014