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
  Purpose

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).


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Alogliptin
Drug: Placebo to alogliptin
Drug: Metformin
Drug: Pioglitazone
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: 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

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 506
Study Start Date: December 2010
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Drug: Placebo to alogliptin
Alogliptin placebo-matching tablets.
Experimental: Alogliptin Monotherapy
Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Drug: Alogliptin
Alogliptin tablets
Other Name: SYR-322
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.
Drug: Placebo to alogliptin
Alogliptin placebo-matching tablets.
Drug: Metformin
Stable metformin dose
Other Names:
  • Fortamet
  • Glucophage
  • Glumetza
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.
Drug: Alogliptin
Alogliptin tablets
Other Name: SYR-322
Drug: Metformin
Stable metformin dose
Other Names:
  • Fortamet
  • Glucophage
  • Glumetza
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.
Drug: Placebo to alogliptin
Alogliptin placebo-matching tablets.
Drug: Pioglitazone
Stable pioglitazone dose
Other Name: Actos
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.
Drug: Alogliptin
Alogliptin tablets
Other Name: SYR-322
Drug: Pioglitazone
Stable pioglitazone dose
Other Name: Actos

Detailed Description:

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.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01289119

  Show 21 Study Locations
Sponsors and Collaborators
Takeda
Investigators
Study Chair: Professor Study Chair Takeda
  More Information

No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01289119     History of Changes
Other Study ID Numbers: SYR-322_02, U1111-1118-3681, SYR-322_308
Study First Received: February 1, 2011
Results First Received: February 17, 2013
Last Updated: February 17, 2013
Health Authority: China: Ministry of Health
Hong Kong: Department of Health
Taiwan : Food and Drug Administration

Keywords provided by Takeda:
Type 2 Diabetes Mellitus
Drug Therapy

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

ClinicalTrials.gov processed this record on April 15, 2014