Ignite Creation Date:
2024-05-05 @ 5:20 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00432276
Status:
COMPLETED
Last Update Posted:
2013-04-04
First Post:
2007-02-05
Brief Title:
Efficacy of Alogliptin and Pioglitazone in Subjects With Type 2 Diabetes Mellitus
Sponsor:
Takeda
Organization:
Takeda
Study Overview
Official Title:
A Multicenter Randomized Double-Blind Study to Determine the Efficacy and Safety of the Addition of SYR-322 25 mg Versus Dose Titration From 30 mg to 45 mg of Pioglitazone HCl ACTOS in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Control on a Combination of Metformin and 30 mg of Pioglitazone HCl Therapy
Status:
COMPLETED
Status Verified Date:
2013-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of the study is to compare the effect of adding alogliptin once daily QD to the ongoing treatment regimen of pioglitazone HCl and metformin in patients with inadequate glycemic control
Detailed Description:
Despite the introduction of new classes of medications for glycemic control just over half of adults with type 2 diabetes mellitus T2DM achieve a glycosylated hemoglobin level less than 70 the American Diabetes Association recommended glycosylated hemoglobin goal The rising incidence of type 2 diabetes mellitus along with limitations of the currently available treatments suggest the need for new therapies for glycemic control along with the increased requirement for combination therapy in type 2 diabetes mellitus
Thiazolidinediones increase glucose utilization decrease gluconeogenesis and increase glucose disposal through an incompletely understood mechanism but one associated with binding of the drug to nuclear receptors known as peroxisome proliferator-activated receptors-gamma Peroxisome proliferator-activated receptors-gamma are found in tissues important for insulin action such as adipose tissue skeletal muscle and the liver The greatest concentration of peroxisome proliferator-activated receptors-gamma receptors is in adipose tissue Thiazolidinediones reduce insulin resistance by enhancing insulin sensitivity in muscle cells adipose tissue and hepatic cells inhibiting hepatic gluconeogenesis with no direct impact on insulin secretion Thus thiazolidinediones improve glycemic control and result in reduced levels of circulating insulin Pioglitazone HCl ACTOS is a thiazolidinedione developed by Takeda Chemical Industries Ltd Osaka Japan Pioglitazone depends on the presence of insulin for its mechanism of action Worldwide clinical investigation has shown that as an adjunct to diet and exercise pioglitazone improves glycemic control when used as monotherapy and in combination with commonly used antidiabetic medications ie sulfonylureas metformin or insulin
SYR-322 alogliptin is a selective orally available inhibitor of dipeptidyl peptidase IV currently in development by Takeda Global Research Development Center Inc as a treatment for type 2 diabetes mellitus Dipeptidyl peptidase IV is the primary enzyme involved in the in vivo degradation of at least 2 peptide hormones released in response to nutrient ingestion namely glucagon-like peptide-1 and glucose-dependent insulinotropic peptide Both peptides exert important effects on islet β-cells to stimulate glucose-dependent insulin secretion and regulate β-cell proliferation and cytoprotection Glucagon-like peptide-1 also inhibits gastric emptying glucagon secretion and food intake The glucose-lowering actions of glucagon-like peptide-1 but not glucose-dependent insulinotropic peptide are preserved in patients with type 2 diabetes
Given the complementary mechanisms of action of alogliptin stimulation of insulin secretion and pioglitazone enhancement of insulin sensitivity and the absence of overlapping safety risks the introduction of this combination therapy in patients with T2DM could potentially show enhanced glycemic control and allow patients to reach and maintain their HbA1c goal more effectively
This study is designed to determine if the addition of alogliptin to a combination of pioglitazone with metformin can be effective at achieving glycemic control without increasing safety risks versus the titration of pioglitazone to 45 mg with metformin in patients with type 2 diabetes mellitus who are experiencing inadequate glycemic control on a current regimen of metformin
Thiazolidinediones increase glucose utilization decrease gluconeogenesis and increase glucose disposal through an incompletely understood mechanism but one associated with binding of the drug to nuclear receptors known as peroxisome proliferator-activated receptors-gamma Peroxisome proliferator-activated receptors-gamma are found in tissues important for insulin action such as adipose tissue skeletal muscle and the liver The greatest concentration of peroxisome proliferator-activated receptors-gamma receptors is in adipose tissue Thiazolidinediones reduce insulin resistance by enhancing insulin sensitivity in muscle cells adipose tissue and hepatic cells inhibiting hepatic gluconeogenesis with no direct impact on insulin secretion Thus thiazolidinediones improve glycemic control and result in reduced levels of circulating insulin Pioglitazone HCl ACTOS is a thiazolidinedione developed by Takeda Chemical Industries Ltd Osaka Japan Pioglitazone depends on the presence of insulin for its mechanism of action Worldwide clinical investigation has shown that as an adjunct to diet and exercise pioglitazone improves glycemic control when used as monotherapy and in combination with commonly used antidiabetic medications ie sulfonylureas metformin or insulin
SYR-322 alogliptin is a selective orally available inhibitor of dipeptidyl peptidase IV currently in development by Takeda Global Research Development Center Inc as a treatment for type 2 diabetes mellitus Dipeptidyl peptidase IV is the primary enzyme involved in the in vivo degradation of at least 2 peptide hormones released in response to nutrient ingestion namely glucagon-like peptide-1 and glucose-dependent insulinotropic peptide Both peptides exert important effects on islet β-cells to stimulate glucose-dependent insulin secretion and regulate β-cell proliferation and cytoprotection Glucagon-like peptide-1 also inhibits gastric emptying glucagon secretion and food intake The glucose-lowering actions of glucagon-like peptide-1 but not glucose-dependent insulinotropic peptide are preserved in patients with type 2 diabetes
Given the complementary mechanisms of action of alogliptin stimulation of insulin secretion and pioglitazone enhancement of insulin sensitivity and the absence of overlapping safety risks the introduction of this combination therapy in patients with T2DM could potentially show enhanced glycemic control and allow patients to reach and maintain their HbA1c goal more effectively
This study is designed to determine if the addition of alogliptin to a combination of pioglitazone with metformin can be effective at achieving glycemic control without increasing safety risks versus the titration of pioglitazone to 45 mg with metformin in patients with type 2 diabetes mellitus who are experiencing inadequate glycemic control on a current regimen of metformin
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U1111-1112-3363 | OTHER | WHO | None |
| 2006-006025-73 | EUDRACT_NUMBER | None | None |