Study of TAK-559 in Treating Subjects With Type 2 Diabetes Mellitus
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|ClinicalTrials.gov Identifier: NCT00762190|
Recruitment Status : Terminated (Hepatic safety signal identified.)
First Posted : September 30, 2008
Last Update Posted : November 12, 2012
|Condition or disease||Intervention/treatment||Phase|
|Diabetes Mellitus||Drug: TAK-559 and insulin Drug: Insulin||Phase 3|
Insulin is a primary regulator of blood glucose concentrations. A subnormal response to circulating insulin levels at target tissues leads to a decrease in insulin-mediated glucose uptake. Insulin resistance is associated with normal to high insulin levels and is often accompanied by dyslipidemia, a disruption in lipid metabolism resulting in increased triglycerides and low-density lipoprotein levels as well as decreased high-density lipoprotein levels in patients with type 2 diabetes mellitus. In the early stages of insulin resistance, a compensatory mechanism of increased insulin secretion by the pancreas maintains normal to near-normal glucose levels. Once the pancreas fails to maintain the increased insulin output, overt type 2 diabetes mellitus occurs.
Insulin also plays an important role in the metabolism of fat and proteins and exerts its influence at the peroxisome proliferator-activated receptor level. Peroxisome proliferator-activated receptor -alpha receptors are expressed predominantly in skeletal muscle, adipose tissue, heart, liver, kidney, gut, macrophages, and vascular tissue, and play a key role in energy storage, glucose homeostasis, and vascular biology. Thus, as insulin activates peroxisome proliferator-activated receptor-alpha receptors, this results in the cellular uptake of glucose. Peroxisome proliferator-activated receptor receptors are ligand-activated transcription elements that regulate gene expression necessary for metabolism. For this reason, peroxisome proliferator-activated receptors play a pivotal role in glucose homeostasis, adipocyte differentiation, and lipid storage. The genes predominantly targeted by transcription activity of activated peroxisome proliferator-activated receptor-alpha receptors are those that mediate fatty acid uptake, fatty acid oxidation, and lipoprotein metabolism. As such, peroxisome proliferator-activated receptor-alpha agonists have their greatest effect on lipid metabolism and vascular biology.
TAK-559 is a novel oxyiminoalkanoic acid under investigation for use as an oral agent in the treatment of patients with type 2 diabetes mellitus. TAK-559 has partial peroxisome proliferator-activated receptor-alpha agonist activity, potent peroxisome proliferator-activated receptor-alpha activity, and modest peroxisome proliferator-activated receptor-gamma activity at high concentrations in nonclinical models.
This study was designed to evaluate the safety of TAK-559 in the treatment of patients with type 2 diabetes mellitus who were on a stable dose of insulin.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||348 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Multicenter, Double-Blind, Placebo-Controlled, Randomized Study of the Safety of TAK-559 in the Treatment of Patients With Type 2 Diabetes Mellitus|
|Study Start Date :||November 2003|
|Actual Primary Completion Date :||December 2004|
|Actual Study Completion Date :||December 2004|
|Experimental: TAK-559 32 mg QD + Insulin||
Drug: TAK-559 and insulin
TAK-559 32 mg, tablets, orally, once daily and insulin stable dose injection for up to 54 weeks.
|Active Comparator: Insulin||
TAK-559 placebo-matching, tablets, orally, once daily and insulin stable dose injection for up to 54 weeks.
- Incidence of Adverse events. [ Time Frame: All visits or at occurrence. ]
- Clinical safety lab tests. [ Time Frame: Weeks 12, 24, and Final Visit. ]
- 12-lead electrocardiogram. [ Time Frame: Weeks: 24 and Final Visit. ]
- Urinalysis. [ Time Frame: Weeks: 12, 24, 36, 48 and Final Visit. ]
- Change from Baseline in Blood pressure and pulse. [ Time Frame: At all visits. ]
- Change from Baseline in Body weight. [ Time Frame: At all visits. ]
- Left ventricular mass index by body surface area measured by echocardiogram. [ Time Frame: Weeks: 24 and Final Visit. ]
- Change from Baseline in total daily dose of insulin. [ Time Frame: At all visits. ]
- Change from Baseline in triglycerides. [ Time Frame: Weeks: 24 and Final Visit. ]
- Change from Baseline in cholesterol. [ Time Frame: Weeks 24 and Final Visit ]
- Change from Baseline in total, high-density lipoproteins. [ Time Frame: Weeks: 24 and Final Visit. ]
- Change from Baseline in low-density lipoproteins. [ Time Frame: Weeks 24 and Final Visit ]
- Change from Baseline in low-density lipoprotein fractionation. [ Time Frame: Weeks 24 and Final Visit ]
- Change from Baseline in very low-density lipoprotein. [ Time Frame: Weeks 24 and Final Visit ]
- Change from Baseline in free fatty acids. [ Time Frame: Weeks 24 and Final Visit ]
- Change from Baseline in apolipoproteins (AI, B). [ Time Frame: Weeks 24 and Final Visit ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00762190
|Study Director:||VP Biological Sciences||Takeda|