Efficacy and Safety of Alogliptin in Participants With Type 2 Diabetes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01289119
First received: February 1, 2011
Last updated: February 17, 2013
Last verified: February 2013

February 1, 2011
February 17, 2013
December 2010
December 2011   (final data collection date for primary outcome measure)
Change From Baseline in Glycosylated Hemoglobin (HbA1c) [ Time Frame: Baseline and Week 16. ] [ 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) collected at Week 16. Least squares means are derived from an analysis of covariance (ANCOVA) model with treatment as a fixed effect, and baseline HbA1c as a covariate for the monotherapy, baseline HbA1c with baseline metformin dose as covariates for the metformin therapy, baseline HbA1c with baseline metformin therapy status and baseline pioglitazone dose as covariates for the pioglitazone therapy.
Change from Baseline in Glycosylated Hemoglobin (Week 16). [ Time Frame: Baseline and Week 16. ] [ Designated as safety issue: No ]
The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 16 or final visit and glycosylated hemoglobin collected at baseline.
Complete list of historical versions of study NCT01289119 on ClinicalTrials.gov Archive Site
  • Change From Baseline in HbA1c Over Time [ Time Frame: Baseline and Weeks 4, 8 and 12. ] [ 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) at Weeks 4, 8 and 12. Least squares means are derived from an analysis of covariance (ANCOVA) model with treatment as a fixed effect, and baseline HbA1c as a covariate for the monotherapy, baseline HbA1c with baseline metformin dose as covariates for the metformin therapy, baseline HbA1c with baseline metformin therapy status and baseline pioglitazone dose as covariates for the pioglitazone therapy.
  • Change From Baseline in Fasting Plasma Glucose Over Time [ Time Frame: Baseline and Weeks 4, 8, 12 and 16. ] [ Designated as safety issue: No ]
    The change from Baseline in fasting plasma glucose (FPG) at Weeks 4, 8, 12 and 16. Least squares means are derived from an ANCOVA model with treatment as a fixed effect, and baseline FPG as a covariate for the monotherapy, baseline FPG with baseline metformin dose as covariates for the metformin therapy, baseline FPG with baseline metformin therapy status and baseline pioglitazone dose as covariates for the pioglitazone therapy.
  • Percentage of Participants With Marked Hyperglycemia [ Time Frame: Randomization to Week 16. ] [ Designated as safety issue: No ]
    Marked Hyperglycemia was defined as fasting plasma glucose greater than or equal to 200 mg/dL (11.1 mmol/L).
  • Change From Baseline in Body Weight [ Time Frame: Baseline and Weeks 8 and 16. ] [ Designated as safety issue: No ]
    The change between body weight measured at Baseline and body weight measured at Weeks 8 and 16. The least squares means are derived from an ANCOVA model with treatment as a fixed effect, and baseline body weight as a covariate for the monotherapy, baseline body weight with baseline metformin dose as covariates for the add-on to metformin therapy, baseline body weight with baseline metformin therapy status and baseline pioglitazone dose as covariates for the add-on to pioglitazone therapy.
  • Percentage of Participants With HbA1c ≤6.5% at Week 16 [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Clinical response was assessed by the percentage of participants with HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) less than or equal to 6.5% at Week 16.
  • Percentage of Participants With HbA1c ≤7.0% at Week 16 [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Clinical response was assessed by the percentage of participants with HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) less than or equal to 7.0% at Week 16.
  • Percentage of Participants With HbA1c ≤7.5% at Week 16 [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Clinical response was assessed by the percentage of participants with HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) less than or equal to 7.5% at Week 16.
  • Percentage of Participants With a Decrease in HbA1c ≥ 0.5% [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    Clinical response was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 0.5% at Week 16.
  • Percentage of Participants With a Decrease in HbA1c ≥1.0% [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    Clinical response was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.0% at Week 16.
  • Percentage of Participants With a Decrease in HbA1c ≥1.5% [ Time Frame: Baseline and Week 16. ] [ Designated as safety issue: No ]
    Clinical response was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.5% at Week 16.
  • Percentage of Participants With a Decrease in HbA1c ≥2.0% [ Time Frame: Baseline and Week 16. ] [ Designated as safety issue: No ]
    Clinical response was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 2.0% at Week 16.
  • Change from Baseline in Glycosylated Hemoglobin at Week 8. [ Time Frame: Baseline and Week 8. ] [ Designated as safety issue: No ]
    The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 8 and glycosylated hemoglobin collected at baseline.
  • Change from Baseline in Glycosylated Hemoglobin at Week 12. [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: No ]
    The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 8 and glycosylated hemoglobin collected at baseline.
  • Change from Baseline in Fasting Plasma Glucose at Week 4. [ Time Frame: Baseline and Week 4. ] [ Designated as safety issue: No ]
    The change between the value of Fasting Plasma Glucose collected at week 4 and Fasting Plasma Glucose collected at baseline.
  • Change from Baseline in Fasting Plasma Glucose at Week 8. [ Time Frame: Baseline and Week 8. ] [ Designated as safety issue: No ]
    The change between the value of Fasting Plasma Glucose collected at week 8 and Fasting Plasma Glucose collected at baseline.
  • Change from Baseline in Fasting Plasma Glucose at Week 12. [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: No ]
    The change between the value of Fasting Plasma Glucose collected at week 12 and Fasting Plasma Glucose collected at baseline.
  • Change from Baseline in Fasting Plasma Glucose at Week 16. [ Time Frame: Baseline and Week 16. ] [ Designated as safety issue: No ]
    The change between the value of Fasting Plasma Glucose collected at week 16 or final visit and Fasting Plasma Glucose collected at baseline.
  • Incidence of marked hyperglycemia (Fasting Plasma Glucose ≥200 mg/dL [11.1 mmol/L]). [ Time Frame: On Occurrence (up to Week 16). ] [ Designated as safety issue: No ]
    Incidence of Marked Hyperglycemia (Fasting Plasma Glucose greater than or equal to 200 mg/dL) is the number of participants who experienced marked hyperglycemia from baseline to week 16 or final visit.
  • Change from Baseline in Body Weight at Week 8. [ Time Frame: Baseline and Week 8. ] [ Designated as safety issue: No ]
    The change between body weight measured at week 8 and body weight measured at baseline.
  • Change from Baseline in Body Weight at Week 16. [ Time Frame: Baseline and Week 16. ] [ Designated as safety issue: No ]
    The change between body weight measured at week 16 or final visit and body weight measured at baseline.
  • Incidence of Glycosylated Hemoglobin ≤6.5% at Week 16. [ Time Frame: Week 16. ] [ Designated as safety issue: No ]
    The incidence of the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 16 or final visit.
  • Incidence of Glycosylated Hemoglobin ≤7.0% at Week 16. [ Time Frame: Week 16. ] [ Designated as safety issue: No ]
    The incidence of the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 16 or final visit.
  • Incidence of Glycosylated Hemoglobin ≤7.5% at Week 16. [ Time Frame: Week 16. ] [ Designated as safety issue: No ]
    The incidence of the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 16 or final visit.
  • Incidence of Glycosylated Hemoglobin decreased from Baseline ≥0.5% at Week 16. [ Time Frame: Baseline and Week 16. ] [ Designated as safety issue: No ]
    The incidence of the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected from baseline to week 16 or final visit.
  • Incidence of Glycosylated Hemoglobin decreased from Baseline ≥1.0% at Week 16. [ Time Frame: Baseline and Week 16. ] [ Designated as safety issue: No ]
    The incidence of the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected from baseline to week 16 or final visit.
  • Incidence of Glycosylated Hemoglobin decreased from Baseline ≥1.5% at Week 16. [ Time Frame: Baseline and Week 16. ] [ Designated as safety issue: No ]
    The incidence of the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected from baseline to week 16 or final visit.
  • Incidence of Glycosylated Hemoglobin decreased from Baseline ≥2.0% at Week 16. [ Time Frame: Baseline and Week 16. ] [ Designated as safety issue: No ]
    The incidence of the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected from baseline to week 16 or final visit.
Not Provided
Not Provided
 
Efficacy and Safety of Alogliptin in Participants With Type 2 Diabetes
An International, Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 3 Study to Determine the Efficacy and Safety of SYR-322 When Used in Subjects With Type 2 Diabetes

The purpose of the study is to determine the efficacy of alogliptin compared to placebo when given alone or as add-on therapy to metformin or add-on to pioglitazone (with or without metformin).

Diabetes is a chronic illness associated with microvascular complications such as nephropathy (kidney disease), retinopathy (eye damage) and neuropathy (nervous system damage). Diabetes is also associated with macrovascular complications including cardiovascular disease (heart disease), stroke and peripheral vascular disease (narrowing or blockage of blood vessels). These complications are associated with reduced quality of life and increased morbidity and mortality.

Takeda is developing SYR-322 (alogliptin) for improvement of glycemic control in patients with Type 2 diabetes mellitus.

Evaluations of alogliptin and its clinical efficacy have been conducted in multiple countries including the United States and Japan. This study will be conducted as a multi-center clinical trial in order to validate the efficacy and safety of alogliptin on type 2 diabetes population within Asia.

Participants who qualified for the study were stratified into 1 of the 3 therapy groups based upon their background antidiabetic therapy before being randomized 1:1 to receive either alogliptin 25 mg once daily or matching placebo once daily.

  • Monotherapy group - patients who had been treated with diet and exercise for at least 2 months prior to screening.
  • Add-on to metformin therapy group - patients who had been treated with metformin for at least 3 months and at a stable dose (≥1000 mg/day) for at least 8 weeks prior to screening.
  • Add-on to pioglitazone therapy group - patients who had been treated with a stable dose of pioglitazone alone or in combination with metformin at a stable dose for at least 8 weeks prior to screening.
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Diabetes Mellitus, Type 2
  • Drug: Alogliptin
    Alogliptin tablets
    Other Name: SYR-322
  • Drug: Placebo to alogliptin
    Alogliptin placebo-matching tablets.
  • Drug: Metformin
    Stable metformin dose
    Other Names:
    • Fortamet
    • Glucophage
    • Glumetza
  • Drug: Pioglitazone
    Stable pioglitazone dose
    Other Name: Actos
  • Placebo Comparator: Placebo
    Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
    Intervention: Drug: Placebo to alogliptin
  • Experimental: Alogliptin Monotherapy
    Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
    Intervention: Drug: Alogliptin
  • Metformin
    Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
    Interventions:
    • Drug: Placebo to alogliptin
    • Drug: Metformin
  • Experimental: Metformin + Alogliptin Add-on Therapy
    Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
    Interventions:
    • Drug: Alogliptin
    • Drug: Metformin
  • Pioglitazone
    Participants continued to receive their stable dose of pioglitazone with or without metformin, and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
    Interventions:
    • Drug: Placebo to alogliptin
    • Drug: Pioglitazone
  • Experimental: Pioglitazone + Alogliptin Add-on Therapy
    Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin, 25 mg tablets orally once daily for up to 16 weeks.
    Interventions:
    • Drug: Alogliptin
    • Drug: Pioglitazone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
506
December 2011
December 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Has a historical diagnosis of Type 2 Diabetes Mellitus.
  • Has a body mass index between acceptable range.
  • Is experiencing inadequate glycemic control.
  • Body weight keeps constant.
  • Females of childbearing potential and males who are sexually active agree to use routinely adequate contraception from signing of informed consent throughout the duration of the study and for 30 days after last dose.

Exclusion Criteria:

  • Has participated in another clinical study within the past 90 days or has received any investigational compound within 30 days prior to randomization.
  • Has a systolic blood pressure beyond the acceptable range at Screening visit.
  • Has New York Heart Association Class III or IV heart failure regardless of therapy.
  • Has any major illness or debility that in the investigator's opinion prohibits the subject from completing the study.
  • Has a history of hypersensitivity or allergies to any DPP-4 inhibitor.
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
China,   Hong Kong,   Taiwan
 
NCT01289119
SYR-322_02, U1111-1118-3681, SYR-322_308
No
Takeda
Takeda
Not Provided
Study Chair: Professor Study Chair Takeda
Takeda
February 2013

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