Ignite Creation Date:
2025-12-24 @ 6:51 PM
Ignite Modification Date:
2026-01-01 @ 12:06 PM
Study NCT ID:
NCT00762957
Status:
TERMINATED
Last Update Posted:
2012-02-28
First Post:
2008-09-26
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Safety and Efficacy of TAK-559 in Combination With Metformin in Patients With Type 2 Diabetes Mellitus.
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003920', 'term': 'Diabetes Mellitus'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D003924', 'term': 'Diabetes Mellitus, Type 2'}, {'id': 'D003923', 'term': 'Diabetes Mellitus, Lipoatrophic'}, {'id': 'D050171', 'term': 'Dyslipidemias'}], 'ancestors': [{'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D052439', 'term': 'Lipid Metabolism Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C488478', 'term': '(E)-4-(4-((5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy)benzyloxyimino)-4-phenylbutyric acid'}, {'id': 'D008687', 'term': 'Metformin'}], 'ancestors': [{'id': 'D001645', 'term': 'Biguanides'}, {'id': 'D006146', 'term': 'Guanidines'}, {'id': 'D000578', 'term': 'Amidines'}, {'id': 'D009930', 'term': 'Organic Chemicals'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 15}}, 'statusModule': {'whyStopped': 'Hepatic Safety Signal Identified.', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2004-11'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2012-02', 'completionDateStruct': {'date': '2004-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2012-02-24', 'studyFirstSubmitDate': '2008-09-26', 'studyFirstSubmitQcDate': '2008-09-26', 'lastUpdatePostDateStruct': {'date': '2012-02-28', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2008-09-30', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2004-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change from baseline in glycosylated hemoglobin.', 'timeFrame': 'Final Visit.'}], 'secondaryOutcomes': [{'measure': 'Change from baseline in glycosylated hemoglobin.', 'timeFrame': 'Weeks 2, 4, 8, 12, 16 and 20'}, {'measure': 'Change from baseline in fasting plasma glucose.', 'timeFrame': 'Weeks 2, 4, 8, 12, 16, 20 and Final Visit'}, {'measure': 'Change from baseline in serum insulin.', 'timeFrame': 'Weeks 4, 12, 16, 20 and Final Visit.'}, {'measure': 'Change from baseline in C-peptide.', 'timeFrame': 'Weeks 4, 12, 16, 20 and Final Visit.'}, {'measure': 'Change from baseline in triglycerides.', 'timeFrame': 'Weeks 12, 16, 20 and Final Visit.'}, {'measure': 'Change from baseline in total cholesterol.', 'timeFrame': 'Weeks 12, 16, 20 and Final Visit.'}, {'measure': 'Change from baseline in high-density lipoprotein.', 'timeFrame': 'Weeks 12, 16, 20 and Final Visit.'}, {'measure': 'Change from baseline in low-density lipoprotein.', 'timeFrame': 'Weeks 12, 16, 20 and Final Visit.'}, {'measure': 'Change from baseline in very-low-density lipoprotein.', 'timeFrame': 'Weeks 12, 16, 20 and Final Visit.'}, {'measure': 'Change from baseline in apolipoproteins A1 and B 100.', 'timeFrame': 'Final Visit'}, {'measure': 'Change from baseline in free fatty acids.', 'timeFrame': 'Weeks 12, 16, 20 and Final Visit.'}, {'measure': 'Change from baseline in thrombosis marker plasminogen activator inhibitor-1', 'timeFrame': 'Weeks 4, 12, 16, 20 and Final Visit'}, {'measure': 'Change from baseline in thrombosis marker fibrinogen.', 'timeFrame': 'Weeks 4, 12, 16, 20 and Final Visit'}, {'measure': 'Change from baseline in inflammation marker Interleukin-6.', 'timeFrame': 'Weeks 4, 12, 16, 20 and Final Visit'}, {'measure': 'Change from baseline in inflammation marker C-reactive protein.', 'timeFrame': 'Weeks 4, 12, 16, 20 and Final Visit'}, {'measure': 'Change from baseline in urinary albumin to creatinine ratio.', 'timeFrame': 'Weeks 12, 16, 20 and Final Visit'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Glucose Metabolism Disorder', 'Dysmetabolic Syndrome', 'Type II Diabetes', 'Diabetes Mellitus, Lipoatrophic', 'Dyslipidemia', 'Drug Therapy'], 'conditions': ['Diabetes Mellitus']}, 'descriptionModule': {'briefSummary': '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', 'detailedDescription': '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.\n\nInsulin 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.\n\nTAK-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.\n\nThis 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '25 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Diagnosed with type 2 diabetes mellitus, and on a stable dose of an oral antidiabetic monotherapy before Screening A.\n* 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.\n* Had a glycosylated hemoglobin level greater than or equal to 8.0% and less than or equal to 10.0% at Screening B.\n* Had a fasting plasma glucose greater than or equal to 126 mg/dL (7.0 mmol/L) at Screening B.\n* Taking a stable dose of at least 1000 mg of metformin for at least 30 days before Screening B.\n* Had a stable or worsening self-monitoring blood glucose level while taking metformin.\n* Had a low-density lipoprotein less than 160 mg/dL (4.1 mmol/L) at Screening A.\n* Had a body mass index was less than or equal to 45 kg/m2 at Screening A.\n* Was willing to be counseled by the investigator or designee to follow an individualized, weight-maintaining diet during the study period.\n* 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.\n* Was able to perform daily self-monitoring blood glucose tests throughout the study.\n* 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.\n* 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.\n* 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.\n\nExclusion Criteria:\n\n* Diagnosed with type 1 diabetes mellitus, hemochromatosis, or had a history of ketoacidosis.\n* Had any condition known to invalidate glycosylated hemoglobin results (eg, hemolytic states or hemoglobinopathies).\n* Took any disallowed medication, prescription medication, herbal treatment or over-the counter medication that may have interfered with evaluation of the study medication, including:\n\n * Insulin\n * Oral antidiabetics including sulfonylureas and alpha-glucosidase inhibitors\n * Systemic corticosteroids\n * Warfarin\n * Rifampin\n * St. John's Wort.\n * Thiazolidinediones\n * Peroxisome proliferator-activated receptor agonists\n * Nicotinic Acid\n * Fibrates\n* 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.\n* Had abdominal, thoracic, or vascular surgery within 6 months before Screening A that in the investigator's opinion warranted exclusion from the study.\n* Had a creatine phosphokinase value greater than 3 times the upper limit of normal at Screening A.\n* Had persistent unexplained microscopic or macroscopic hematuria or a history of bladder cancer.\n* Had a triglyceride level greater than 500 mg/dL (5.6 mmol/L) at Screening A.\n* 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.\n* Donated and/or received any blood or blood products within 3 months before Randomization.\n* Had a history of drug abuse or a history of alcohol abuse within 2 years before Randomization\n* Had a systolic blood pressure greater than 140 mm Hg or a diastolic blood pressure of greater than 95 mm Hg at Screening B.\n* Had significant cardiovascular disease including but not limited to, New York Heart Association Functional (Cardiac) Classification III or IV.\n* 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.\n* 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.\n* Had a positive anti-hepatitis B surface antigen, or anti-hepatitis B e antigen test results at Screening A.\n* Was currently taking another investigational study medication or had taken an investigational study medication within 30 days before Screening A.\n* 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."}, 'identificationModule': {'nctId': 'NCT00762957', 'briefTitle': 'Safety and Efficacy of TAK-559 in Combination With Metformin in Patients With Type 2 Diabetes Mellitus.', 'organization': {'class': 'INDUSTRY', 'fullName': 'Takeda'}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': '01-04-TL-559-029'}, 'secondaryIdInfos': [{'id': 'U1111-1128-4945', 'type': 'REGISTRY', 'domain': 'WHO'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'TAK-559 16 mg QD + Metformin QD', 'interventionNames': ['Drug: TAK-559 and metformin']}, {'type': 'EXPERIMENTAL', 'label': 'TAK-559 32 mg QD + Metformin QD', 'interventionNames': ['Drug: TAK-559 and metformin']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Metformin QD', 'interventionNames': ['Drug: Metformin']}], 'interventions': [{'name': 'TAK-559 and metformin', 'type': 'DRUG', 'description': 'TAK-559 16 mg, tablets, orally, once daily and metformin stable dose orally, once daily for up to 26 weeks.', 'armGroupLabels': ['TAK-559 16 mg QD + Metformin QD']}, {'name': 'TAK-559 and metformin', 'type': 'DRUG', 'description': 'TAK-559 32 mg, tablets, orally, once daily and metformin stable dose, orally, once daily for up to 26 weeks.', 'armGroupLabels': ['TAK-559 32 mg QD + Metformin QD']}, {'name': 'Metformin', 'type': 'DRUG', 'description': 'TAK-559 placebo-matching tablets, orally, once daily and metformin stable dose, orally, once daily for up to 26 weeks.', 'armGroupLabels': ['Metformin QD']}]}, 'contactsLocationsModule': {'overallOfficials': [{'name': 'VP Biological Sciences', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Takeda'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Takeda', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}