Study of TAK-559 in Treating Subjects With Type 2 Diabetes Mellitus
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|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|
- 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 ]
|Study Start Date:||November 2003|
|Study Completion Date:||December 2004|
|Primary Completion Date:||December 2004 (Final data collection date for primary outcome measure)|
|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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00762190
|Study Director:||VP Biological Sciences||Takeda|