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).

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Alogliptin; Drug: Placebo to alogliptin; Drug: Metformin; Drug: Pioglitazone

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 Type: Interventional
• Enrollment (Actual): 506
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: SYR-322
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.	Drug: Placebo to alogliptin; Alogliptin placebo-matching tablets.; Drug: Metformin; Stable metformin dose; Other Names: Glucophage; Glumetza; Fortamet
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 Names: SYR-322; Drug: Metformin; Stable metformin dose; Other Names: Glucophage; Glumetza; Fortamet
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.	Drug: Placebo to alogliptin; Alogliptin placebo-matching tablets.; Drug: Pioglitazone; Stable pioglitazone dose; Other Names: 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 Names: SYR-322; Drug: Pioglitazone; Stable pioglitazone dose; Other Names: Actos

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Glycosylated Hemoglobin (HbA1c)	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.	Baseline and Week 16.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HbA1c Over Time	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.	Baseline and Weeks 4, 8 and 12.
Change From Baseline in Fasting Plasma Glucose Over Time	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.	Baseline and Weeks 4, 8, 12 and 16.
Percentage of Participants With Marked Hyperglycemia	Marked Hyperglycemia was defined as fasting plasma glucose greater than or equal to 200 mg/dL (11.1 mmol/L).	Randomization to Week 16.
Change From Baseline in Body Weight	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.	Baseline and Weeks 8 and 16.
Percentage of Participants With HbA1c ≤6.5% at Week 16	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.	Week 16
Percentage of Participants With HbA1c ≤7.0% at Week 16	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.	Week 16
Percentage of Participants With HbA1c ≤7.5% at Week 16	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.	Week 16
Percentage of Participants With a Decrease in HbA1c ≥ 0.5%	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.	Baseline and Week 16
Percentage of Participants With a Decrease in HbA1c ≥1.0%	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.	Baseline and Week 16
Percentage of Participants With a Decrease in HbA1c ≥1.5%	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.	Baseline and Week 16.
Percentage of Participants With a Decrease in HbA1c ≥2.0%	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.	Baseline and Week 16.

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Chair: Professor Study Chair, Takeda

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: February 1, 2011
• First Submitted That Met QC Criteria: February 1, 2011
• First Posted (Estimate): February 3, 2011

Study Record Updates

• Last Update Posted (Estimate): March 22, 2013
• Last Update Submitted That Met QC Criteria: February 17, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: Drug Therapy; Type 2 Diabetes Mellitus
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Pioglitazone; Alogliptin
• Other Study ID Numbers: SYR-322_02; U1111-1118-3681 (Registry Identifier: WHO); SYR-322_308 (Other Identifier: Takeda ID)