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

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ClinicalTrials.gov Identifier: NCT01023581
Recruitment Status : Completed
First Posted : December 2, 2009
Results First Posted : March 26, 2013
Last Update Posted : March 26, 2013
Sponsor:
Information provided by (Responsible Party):
Takeda

Tracking Information
First Submitted Date  ICMJE December 1, 2009
First Posted Date  ICMJE December 2, 2009
Results First Submitted Date  ICMJE February 17, 2013
Results First Posted Date  ICMJE March 26, 2013
Last Update Posted Date March 26, 2013
Study Start Date  ICMJE November 2009
Actual Primary Completion Date June 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 17, 2013)
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 [ Time Frame: Baseline and Week 26. ]
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).
Original Primary Outcome Measures  ICMJE
 (submitted: December 1, 2009)
Change from Baseline in Glycosylated Hemoglobin at Week 26. [ Time Frame: Baseline and Week 26. ]
Change History Complete list of historical versions of study NCT01023581 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 17, 2013)
  • Change From Baseline in HbA1c Over Time [ Time Frame: Baseline and Weeks 4, 8, 12, 16, and 20. ]
    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. ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 1, 2009)
  • Change from Baseline in Glycosylated Hemoglobin at Week 4. [ Time Frame: Baseline and Week 4. ]
  • Change from Baseline in Glycosylated Hemoglobin at Week 8. [ Time Frame: Baseline and Week 8. ]
  • Change from Baseline in Glycosylated Hemoglobin at Week 12. [ Time Frame: Baseline and Week 12 ]
  • Change from Baseline in Glycosylated Hemoglobin at Week 16. [ Time Frame: Baseline and Week 16. ]
  • Change from Baseline in Glycosylated Hemoglobin at Week 20. [ Time Frame: Baseline and Week 20. ]
  • Change from Baseline in Fasting Plasma Glucose at Week 1. [ Time Frame: Baseline and Week 1. ]
  • Change from Baseline in Fasting Plasma Glucose at Week 2. [ Time Frame: Baseline and Week 2. ]
  • Change from Baseline in Fasting Plasma Glucose at Week 4. [ Time Frame: Baseline and Week 4. ]
  • Change from Baseline in Fasting Plasma Glucose at Week 8. [ Time Frame: Baseline and Week 8. ]
  • Change from Baseline in Fasting Plasma Glucose at Week 12. [ Time Frame: Baseline and Week 12. ]
  • Change from Baseline in Fasting Plasma Glucose at Week 16. [ Time Frame: Baseline and Week 16. ]
  • Change from Baseline in Fasting Plasma Glucose at Week 20. [ Time Frame: Baseline and Week 20. ]
  • Change from Baseline in Fasting Plasma Glucose at Week 26. [ Time Frame: Baseline and Week 26. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Alogliptin Plus Metformin in Patients With Type 2 Diabetes
Official Title  ICMJE 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
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Diabetes Mellitus, Type 2
Intervention  ICMJE
  • Drug: Alogliptin
    Alogliptin tablets.
    Other Name: SYR-322
  • Drug: Metformin
    Metformin capsules
    Other Names:
    • Glucophage
    • Glucophage XR
    • Riomet
    • Fortamet
    • Glumetza
    • Obimet
    • Dianben
    • Diabex
    • Diaformin
  • Drug: Alogliptin Placebo
    Alogliptin placebo-matching tablets.
  • Drug: Metformin Placebo
    Metformin placebo-matching capsules.
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Alogliptin placebo-matching tablets, orally, twice daily and Metformin placebo-matching capsules, orally, twice daily for up to 26 weeks.
    Interventions:
    • Drug: Alogliptin Placebo
    • Drug: Metformin Placebo
  • 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.
    Interventions:
    • Drug: Alogliptin
    • Drug: Metformin Placebo
  • 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.
    Interventions:
    • Drug: Alogliptin
    • Drug: Metformin Placebo
  • 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.
    Interventions:
    • Drug: Metformin
    • Drug: Alogliptin Placebo
  • 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.
    Interventions:
    • Drug: Metformin
    • Drug: Alogliptin Placebo
  • 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.
    Interventions:
    • Drug: Alogliptin
    • Drug: Metformin
  • 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.
    Interventions:
    • Drug: Alogliptin
    • Drug: Metformin
Publications * Pratley RE, Fleck P, Wilson C. Efficacy and safety of initial combination therapy with alogliptin plus metformin versus either as monotherapy in drug-naïve patients with type 2 diabetes: a randomized, double-blind, 6-month study. Diabetes Obes Metab. 2014 Jul;16(7):613-21. doi: 10.1111/dom.12258. Epub 2014 Feb 12.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 6, 2011)
784
Original Estimated Enrollment  ICMJE
 (submitted: December 1, 2009)
735
Actual Study Completion Date  ICMJE June 2011
Actual Primary Completion Date June 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Czech Republic,   Hungary,   Israel,   Lithuania,   Mexico,   Poland,   Puerto Rico,   Romania,   Russian Federation,   Slovakia,   South Africa,   Ukraine,   United States
Removed Location Countries Chile,   Guatemala,   India,   Peru
 
Administrative Information
NCT Number  ICMJE NCT01023581
Other Study ID Numbers  ICMJE SYR-322MET_302
2009-012652-24 ( Registry Identifier: EudraCT )
U1111-1112-1912 ( Registry Identifier: WHO )
DOH-27-0910-3155 ( Registry Identifier: SANCTR )
CTRI/2010/091/000253 ( Registry Identifier: CTRI )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Takeda
Study Sponsor  ICMJE Takeda
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Vice President, Clinical Science Takeda
PRS Account Takeda
Verification Date February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP