Efficacy of TAK-559 in Treating Subjects With Type 2 Diabetes Mellitus
Primary Purpose
Diabetes Mellitus
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
TAK-559
TAK-559
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus focused on measuring Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Drug Therapy
Eligibility Criteria
Inclusion Criteria:
- Is diagnosed with type 2 diabetes mellitus using American Diabetes Association diagnostic criteria, and on a stable dose of an oral anti-diabetic monotherapy prior to Screening A.
- 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.
- Was taking a stable dose of at least 10 mg of glyburide for at least 10 days prior to Screening B.
- Was on a stable or worsening self-monitoring blood glucose level while taking glyburide.
- Had a low-density lipoprotein less than 160 mg/dL (4.1 mmol/L) at Screening A.
- Had a body mass index 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 uIU/mL (5.5 mIU/L) and greater than or equal to 0.35 uIU/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 evaluations within the normal reference range for the testing laboratory, or if not, the results must be deemed not clinically significant by the investigator prior to Randomization.
- Females were post menopausal, surgically sterile, or using adequate contraception.
Exclusion Criteria:
- Was diagnosed with type 1 diabetes mellitus, hemochromatosis, or has a history of ketoacidosis.
- Had any condition known to invalidate glycosylated hemoglobin results (eg, hemolytic states, hemoglobinopathies).
Was required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:
- Insulin
- Oral anti-diabetics other than TAK-559 (including sulfonylureas other than glyburide, alpha-glucosidase inhibitors, metformin)
- 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 prior to Screening A.
- Had abdominal, thoracic, or vascular surgery within 6 months prior to Screening A that in the investigator's opinion would warrant exclusion from the study.
- Had a creatine phosphokinase value greater than 3 times the upper limit of normal at Screening A. The creatine phosphokinase value can be retested prior to Randomization if elevated.
- 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.
- Had any alteration in allowed lipid lowering medication (dose or drug) within 2 months of Randomization, if applicable.
- Had donated and/or received any blood or blood products within 3 months prior to Randomization.
- Had a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within 2 years prior to Randomization.
- Had a systolic BP 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 previous history of cancer, other than basal cell or stage 1 squamous cell carcinoma of the skin, that has not been in remission within 5 years prior to Randomization.
- Had an alanine transaminase or aspartate transaminase level greater than 3 times the upper limit of normal, active liver disease, or jaundice at Screening A.
- Had a positive human immunodeficiency virus, hepatitis B surface antigen, or hepatitis B e antigen test at Screening A.
- Had any other serious disease or condition at Screening A or at Randomization that might affect life expectancy or make it difficult to successfully manage and follow the patient according to the protocol.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
TAK-559 16 mg QD
TAK-559 32mg QD
Placebo QD
Arm Description
Outcomes
Primary Outcome Measures
Change in Baseline in Glycosylated hemoglobin.
Secondary Outcome Measures
Change in Baseline in Glycosylated hemoglobin.
Change in Baseline in Fasting Plasma Glucose.
Change in Baseline in Serum insulin.
Change in Baseline in C-peptide.
Change in Baseline in Lipids (triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, very-low-density lipoprotein).
Change in Baseline in Lipids (low-density lipoprotein fractionation).
Change in Baseline in Apolipoproteins Al and B100.
Change in Baseline in Free fatty acids.
Markers of thrombosis (plasminogen activator inhibitor-i).
Markers of thrombosis (fibrinogen).
Markers of inflammation (interleukin-6).
Markers of inflammation (C-reactive protein).
Urinary albumin/creatinine ratio.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00763022
Brief Title
Efficacy of TAK-559 in Treating Subjects With Type 2 Diabetes Mellitus
Official Title
A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel Study of the Safety and Efficacy of TAK-559 Compared to Placebo in the Treatment of Patients With Type 2 Diabetes Mellitus
Study Type
Interventional
2. Study Status
Record Verification Date
November 2012
Overall Recruitment Status
Completed
Study Start Date
November 2003 (undefined)
Primary Completion Date
December 2004 (Actual)
Study Completion Date
December 2004 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study was to determine the safety and efficacy of TAK-559, once daily (QD), in Type 2 Diabetes subjects.
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.
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 whose symptoms were managed by diet and exercise.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus
Keywords
Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Drug Therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
302 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TAK-559 16 mg QD
Arm Type
Experimental
Arm Title
TAK-559 32mg QD
Arm Type
Experimental
Arm Title
Placebo QD
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
TAK-559
Intervention Description
TAK-559 16 mg, tablets, orally, once daily for up to 26 weeks.
Intervention Type
Drug
Intervention Name(s)
TAK-559
Intervention Description
TAK-559 32 mg, tablets, orally, once daily for up to 26 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
TAK-559 placebo-matching tablets, orally, once daily for up to 26 weeks.
Primary Outcome Measure Information:
Title
Change in Baseline in Glycosylated hemoglobin.
Time Frame
Weeks: 4, 8, 12, 16, 20 and Final Visit.
Secondary Outcome Measure Information:
Title
Change in Baseline in Glycosylated hemoglobin.
Time Frame
Weeks: 4, 8, 12, 16, 20 and Final Visit.
Title
Change in Baseline in Fasting Plasma Glucose.
Time Frame
Weeks: 2, 4, 8, 12, 16, 20 and Final Visit.
Title
Change in Baseline in Serum insulin.
Time Frame
Weeks: 4, 12, 16, 20 and Final Visit.
Title
Change in Baseline in C-peptide.
Time Frame
Weeks: 4, 12, 16, 20 and Final Visit.
Title
Change in Baseline in Lipids (triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, very-low-density lipoprotein).
Time Frame
Weeks: 12, 16, 20 and Final Visit.
Title
Change in Baseline in Lipids (low-density lipoprotein fractionation).
Time Frame
Weeks: 12, 16, 20 and Final Visit.
Title
Change in Baseline in Apolipoproteins Al and B100.
Time Frame
Final Visit.
Title
Change in Baseline in Free fatty acids.
Time Frame
Weeks: 12, 16, 20 and Final Visit.
Title
Markers of thrombosis (plasminogen activator inhibitor-i).
Time Frame
Weeks: 4, 12, 16, 20 and Final Visit.
Title
Markers of thrombosis (fibrinogen).
Time Frame
Weeks: 4, 12, 16, 20 and Final Visit.
Title
Markers of inflammation (interleukin-6).
Time Frame
Weeks: 4, 12, 16, 20 and Final Visit.
Title
Markers of inflammation (C-reactive protein).
Time Frame
Weeks: 4, 12, 16, 20 and Final Visit.
Title
Urinary albumin/creatinine ratio.
Time Frame
Weeks: 12, 16, 20 and Final Visit.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Is diagnosed with type 2 diabetes mellitus using American Diabetes Association diagnostic criteria, and on a stable dose of an oral anti-diabetic monotherapy prior to Screening A.
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.
Was taking a stable dose of at least 10 mg of glyburide for at least 10 days prior to Screening B.
Was on a stable or worsening self-monitoring blood glucose level while taking glyburide.
Had a low-density lipoprotein less than 160 mg/dL (4.1 mmol/L) at Screening A.
Had a body mass index 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 uIU/mL (5.5 mIU/L) and greater than or equal to 0.35 uIU/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 evaluations within the normal reference range for the testing laboratory, or if not, the results must be deemed not clinically significant by the investigator prior to Randomization.
Females were post menopausal, surgically sterile, or using adequate contraception.
Exclusion Criteria:
Was diagnosed with type 1 diabetes mellitus, hemochromatosis, or has a history of ketoacidosis.
Had any condition known to invalidate glycosylated hemoglobin results (eg, hemolytic states, hemoglobinopathies).
Was required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:
Insulin
Oral anti-diabetics other than TAK-559 (including sulfonylureas other than glyburide, alpha-glucosidase inhibitors, metformin)
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 prior to Screening A.
Had abdominal, thoracic, or vascular surgery within 6 months prior to Screening A that in the investigator's opinion would warrant exclusion from the study.
Had a creatine phosphokinase value greater than 3 times the upper limit of normal at Screening A. The creatine phosphokinase value can be retested prior to Randomization if elevated.
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.
Had any alteration in allowed lipid lowering medication (dose or drug) within 2 months of Randomization, if applicable.
Had donated and/or received any blood or blood products within 3 months prior to Randomization.
Had a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within 2 years prior to Randomization.
Had a systolic BP 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 previous history of cancer, other than basal cell or stage 1 squamous cell carcinoma of the skin, that has not been in remission within 5 years prior to Randomization.
Had an alanine transaminase or aspartate transaminase level greater than 3 times the upper limit of normal, active liver disease, or jaundice at Screening A.
Had a positive human immunodeficiency virus, hepatitis B surface antigen, or hepatitis B e antigen test at Screening A.
Had any other serious disease or condition at Screening A or at Randomization that might affect life expectancy or make it difficult to successfully manage and follow the patient according to the protocol.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sr VP Clinical Science
Organizational Affiliation
Takeda
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
Efficacy of TAK-559 in Treating Subjects With Type 2 Diabetes Mellitus
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