Efficacy and Safety of Alogliptin in Participants With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01289119
• Other study ID #: SYR-322_02
• Secondary ID: U1111-1118-3681S
• Status: Completed
• Phase: Phase 3
• First received: February 1, 2011
• Last updated: February 17, 2013
• Start date: December 2010
• Est. completion date: December 2011

Study information

• Verified date: February 2013
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ministry of HealthHong Kong: Department of HealthTaiwan : Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 506
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Alogliptin
Alogliptin tablets
• Placebo to alogliptin
Alogliptin placebo-matching tablets.
• Metformin
Stable metformin dose
• Pioglitazone
Stable pioglitazone dose

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

China,  Hong Kong,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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.	No
Secondary	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.	No