Efficacy and Safety of Alogliptin in Participants With Type 2 Diabetes

Overview[ - collapse ][ - ]

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).
ConditionDiabetes Mellitus, Type 2
InterventionDrug: Alogliptin
Drug: Placebo to alogliptin
Drug: Metformin
Drug: Pioglitazone
PhasePhase 3
SponsorTakeda
Responsible PartyTakeda
ClinicalTrials.gov IdentifierNCT01289119
First ReceivedFebruary 1, 2011
Last UpdatedFebruary 17, 2013
Last verifiedFebruary 2013

Tracking Information[ + expand ][ + ]

First Received DateFebruary 1, 2011
Last Updated DateFebruary 17, 2013
Start DateDecember 2010
Estimated Primary Completion DateDecember 2011
Current Primary Outcome MeasuresChange 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.
Current 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.

Descriptive Information[ + expand ][ + ]

Brief TitleEfficacy and Safety of Alogliptin in Participants With Type 2 Diabetes
Official TitleAn 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
Brief Summary
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).
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.
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
ConditionDiabetes Mellitus, Type 2
InterventionDrug: Alogliptin
Alogliptin tablets
Other Names:
SYR-322Drug: Placebo to alogliptin
Alogliptin placebo-matching tablets.
Drug: Metformin
Stable metformin dose
Other Names:
  • Fortamet
  • Glucophage
  • Glumetza
Drug: Pioglitazone
Stable pioglitazone dose
Other Names:
Actos
Study Arm (s)
  • Placebo Comparator: Placebo
    Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
  • Experimental: Alogliptin Monotherapy
    Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
  • Other: 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.
  • 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.
  • Other: 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.
  • 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.

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment506
Estimated Completion DateDecember 2011
Estimated Primary Completion DateDecember 2011
Eligibility 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.
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesChina, Hong Kong, Taiwan

Administrative Information[ + expand ][ + ]

NCT Number NCT01289119
Other Study ID NumbersSYR-322_02
Has Data Monitoring CommitteeNo
Information Provided ByTakeda
Study SponsorTakeda
CollaboratorsNot Provided
Investigators Study Chair: Professor Study Chair Takeda
Verification DateFebruary 2013

Locations[ + expand ][ + ]

China, Beijing
Beijing, Beijing, China
China, Fujian
Fuzhou, Fujian, China
China, Fujian
Xiamen, Fujian, China
China, Guangdong
Guangzhou, Guangdong, China
China, Hainan
Haikou, Hainan, China
China, Heilongjiang
Ha'erbin, Heilongjiang, China
China, Hubei
Jingzhou, Hubei, China
China, Hubei
Shiyan, Hubei, China
China, Hunan
Changsha, Hunan, China
China, Jiangsu
Wuxi, Jiangsu, China
China, Jiangxi
Nanchang, Jiangxi, China
China, Jilin
Changchun, Jilin, China
China, Liaoning
Shenyang, Liaoning, China
China, Shandong
Jinan, Shandong, China
China, Shanghai
Shanghai, Shanghai, China
China, Shanxi
Xi'an, Shanxi, China
China, Tianjin
Tianjin, Tianjin, China
China, Yunnan
Kunming, Yunnan, China
China, Zhejiang
Hangzhou, Zhejiang, China
Hong Kong
Hong Kong, Hong Kong
Taiwan
Taipei County, Taiwan