Safety and Efficacy of TAK-559 in Combination With Metformin in Patients With Type 2 Diabetes Mellitus.
Overview[ - collapse ][ - ]
| Purpose | The purpose of this study is to evaluate the safety and efficacy of TAK-559, once daily (QD), taken in combination with metformin in treating subjects with type 2 diabetes mellitus |
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| Condition | Diabetes Mellitus |
| Intervention | Drug: TAK-559 and metformin Drug: TAK-559 and metformin Drug: Metformin |
| Phase | Phase 3 |
| Sponsor | Takeda |
| Responsible Party | Takeda |
| ClinicalTrials.gov Identifier | NCT00762957 |
| First Received | September 26, 2008 |
| Last Updated | February 24, 2012 |
| Last verified | February 2012 |
Tracking Information[ + expand ][ + ]
| First Received Date | September 26, 2008 |
|---|---|
| Last Updated Date | February 24, 2012 |
| Start Date | November 2004 |
| Estimated Primary Completion Date | December 2004 |
| Current Primary Outcome Measures | Change from baseline in glycosylated hemoglobin. [Time Frame: Final Visit.] [Designated as safety issue: No] |
| Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
| Brief Title | Safety and Efficacy of TAK-559 in Combination With Metformin in Patients With Type 2 Diabetes Mellitus. |
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| Official Title | A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel Study of the Safety and Efficacy of a Combination of TAK-559 and Metformin Compared to Placebo and Metformin in the Treatment of Patients With Type 2 Diabetes Mellitus |
| Brief Summary | The purpose of this study is to evaluate the safety and efficacy of TAK-559, once daily (QD), taken in combination with metformin in treating subjects with type 2 diabetes mellitus |
| Detailed Description | 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 and glycemic control of TAK-559 in patients with type 2 diabetes mellitus taking metformin for whom monotherapy with an oral anti-diabetic had been insufficient. |
| Study Type | Interventional |
| Study Phase | Phase 3 |
| Study Design | Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment |
| Condition | Diabetes Mellitus |
| Intervention | Drug: TAK-559 and metformin TAK-559 16 mg, tablets, orally, once daily and metformin stable dose orally, once daily for up to 26 weeks. Drug: TAK-559 and metformin TAK-559 32 mg, tablets, orally, once daily and metformin stable dose, orally, once daily for up to 26 weeks. Drug: Metformin TAK-559 placebo-matching tablets, orally, once daily and metformin stable dose, orally, once daily for up to 26 weeks. |
| Study Arm (s) |
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Recruitment Information[ + expand ][ + ]
| Recruitment Status | Terminated |
|---|---|
| Estimated Enrollment | 15 |
| Estimated Completion Date | December 2004 |
| Estimated Primary Completion Date | December 2004 |
| Eligibility Criteria | Inclusion Criteria: - Diagnosed with type 2 diabetes mellitus, and on a stable dose of an oral antidiabetic monotherapy before Screening A. - Female patients of childbearing potential who were sexually active agreed to use adequate contraception, and could neither pregnant nor lactating from Screening throughout the duration of the study. - Had a glycosylated hemoglobin level greater than or equal to 8.0% and less than or equal to 10.0% at Screening B. - Had a fasting plasma glucose greater than or equal to 126 mg/dL (7.0 mmol/L) at Screening B. - Taking a stable dose of at least 1000 mg of metformin for at least 30 days before Screening B. - Had a stable or worsening self-monitoring blood glucose level while taking metformin. - Had a low-density lipoprotein less than 160 mg/dL (4.1 mmol/L) at Screening A. - Had a body mass index was less than or equal to 45 kg/m2 at Screening A. - Was willing to be counseled by the investigator or designee to follow an individualized, weight-maintaining diet during the study period. - Had evidence of insulin secretory capacity as demonstrated by a C-peptide concentration of greater than or equal to 1.5 ng/mL (0.50 nmol/L) at Screening A, and if necessary, after a repeat at Screening B. - Was able to perform daily self-monitoring blood glucose tests throughout the study. - Had a normal thyroid-stimulating hormone level of less than 5.5 μIU/mL (5.5 mIU/L) and greater than or equal to 0.35 μIU/mL (0.35 mIU/L) at Screening A. - Was in good health as determined by a physician (ie, via medical history and physical examination), other than a diagnosis of type 2 diabetes mellitus. - Had fasting clinical laboratory results within the normal ranges for the testing laboratory, or if not, the results were deemed not clinically significant by the investigator before Randomization. Exclusion Criteria: - Diagnosed with type 1 diabetes mellitus, hemochromatosis, or had a history of ketoacidosis. - Had any condition known to invalidate glycosylated hemoglobin results (eg, hemolytic states or hemoglobinopathies). - Took any disallowed medication, prescription medication, herbal treatment or over-the counter medication that may have interfered with evaluation of the study medication, including: - Insulin - Oral antidiabetics including sulfonylureas and alpha-glucosidase inhibitors - Systemic corticosteroids - Warfarin - Rifampin - St. John's Wort. - Thiazolidinediones - Peroxisome proliferator-activated receptor agonists - Nicotinic Acid - Fibrates - Had a history of myocardial infarction, coronary angioplasty or bypass graft, unstable angina pectoris, transient ischemic attacks, clinically significant abnormal electrocardiogram, or documented cerebrovascular accident within 6 months before Screening A. - Had abdominal, thoracic, or vascular surgery within 6 months before Screening A that in the investigator's opinion warranted exclusion from the study. - Had a creatine phosphokinase value greater than 3 times the upper limit of normal at Screening A. - Had persistent unexplained microscopic or macroscopic hematuria or a history of bladder cancer. - Had a triglyceride level greater than 500 mg/dL (5.6 mmol/L) at Screening A. - Received any alteration in allowed lipid lowering medication (dose or drug) within 2 months of Randomization, if applicable. The patient remained on a stable dose throughout the study. If deemed necessary, the dose could have been lowered with prior approval from the Sponsor. - Donated and/or received any blood or blood products within 3 months before Randomization. - Had a history of drug abuse or a history of alcohol abuse within 2 years before Randomization - Had a systolic blood pressure greater than 140 mm Hg or a diastolic blood pressure of greater than 95 mm Hg at Screening B. - Had significant cardiovascular disease including but not limited to, New York Heart Association Functional (Cardiac) Classification III or IV. - Had a history of cancer other than basal cell or stage 1 squamous cell carcinoma of the skin that had not been in remission within 5 years before Randomization. - Had an alanine aminotransferase or aspartate aminotransferase level greater than 3 times the upper limit of normal, active liver disease, or jaundice at Screening A. - Had a positive anti-hepatitis B surface antigen, or anti-hepatitis B e antigen test results at Screening A. - Was currently taking another investigational study medication or had taken an investigational study medication within 30 days before Screening A. - Had any other serious disease or condition at Screening A or at Randomization that might have affected life expectancy or made it difficult to successfully manage and follow the patient according to the protocol. |
| Gender | Both |
| Ages | 25 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | Not Provided |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00762957 |
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| Other Study ID Numbers | 01-04-TL-559-029 |
| Has Data Monitoring Committee | No |
| Information Provided By | Takeda |
| Study Sponsor | Takeda |
| Collaborators | Not Provided |
| Investigators | Study Director: VP Biological Sciences Takeda |
| Verification Date | February 2012 |