Diabetes MellitusPhase 3NCT00762957
Safety and Efficacy of TAK-559 in Combination With Metformin in Patients With Type 2 Diabetes Mellitus.
A Phase 3 study testing TAK-559 and metformin and Metformin in people with Diabetes Mellitus, run by Takeda.
Trial 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 Read more about this study
- Who is it for?
- Ages 25 to 75 years
- Conditions the study is for
- Diabetes Mellitus
- What is being tested?
- TAK-559 and metformin and Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- No sites listed yet
- Study dates
- Nov 2004to Dec 2004
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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.
About this study
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
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
Read the 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.
- Conditions
- Diabetes Mellitus
- Being tested
- TAK-559 and metformin, Metformin
- Keywords
- Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Drug Therapy
- Medical subject headings
- Diabetes Mellitus, Glucose Metabolism Disorders, Diabetes Mellitus, Type 2, Diabetes Mellitus, Lipoatrophic, Dyslipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAK-559 and metforminDrug
TAK-559 16 mg, tablets, orally, once daily and metformin stable dose orally, once daily for up to 26 weeks.
TAK-559 and metforminDrug
TAK-559 32 mg, tablets, orally, once daily and metformin stable dose, orally, once daily for up to 26 weeks.
MetforminDrug
TAK-559 placebo-matching tablets, orally, once daily and metformin stable dose, orally, once daily for up to 26 weeks.
| Study group | Role | What they receive |
|---|---|---|
| TAK-559 16 mg QD + Metformin QD | Experimental | Not described Receives: Drug: TAK-559 and metformin |
| TAK-559 32 mg QD + Metformin QD | Experimental | Not described Receives: Drug: TAK-559 and metformin |
| Metformin QD | Active comparator | Not described Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in glycosylated hemoglobin.
Measured: Final Visit.
Secondary outcomes (16)
Change from baseline in glycosylated hemoglobin.
Measured: Weeks 2, 4, 8, 12, 16 and 20
Change from baseline in fasting plasma glucose.
Measured: Weeks 2, 4, 8, 12, 16, 20 and Final Visit
Change from baseline in serum insulin.
Measured: Weeks 4, 12, 16, 20 and Final Visit.
Change from baseline in C-peptide.
Measured: Weeks 4, 12, 16, 20 and Final Visit.
Change from baseline in triglycerides.
Measured: Weeks 12, 16, 20 and Final Visit.
Change from baseline in total cholesterol.
Measured: Weeks 12, 16, 20 and Final Visit.
Change from baseline in high-density lipoprotein.
Measured: Weeks 12, 16, 20 and Final Visit.
Change from baseline in low-density lipoprotein.
Measured: Weeks 12, 16, 20 and Final Visit.
Change from baseline in very-low-density lipoprotein.
Measured: Weeks 12, 16, 20 and Final Visit.
Change from baseline in apolipoproteins A1 and B 100.
Measured: Final Visit
Change from baseline in free fatty acids.
Measured: Weeks 12, 16, 20 and Final Visit.
Change from baseline in thrombosis marker plasminogen activator inhibitor-1
Measured: Weeks 4, 12, 16, 20 and Final Visit
Change from baseline in thrombosis marker fibrinogen.
Measured: Weeks 4, 12, 16, 20 and Final Visit
Change from baseline in inflammation marker Interleukin-6.
Measured: Weeks 4, 12, 16, 20 and Final Visit
Change from baseline in inflammation marker C-reactive protein.
Measured: Weeks 4, 12, 16, 20 and Final Visit
Change from baseline in urinary albumin to creatinine ratio.
Measured: Weeks 12, 16, 20 and Final Visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2008 (estimated)
- Study startNov 2004
- Primary completionDec 2004
- Study completionDec 2004
Why it stopped: Hepatic Safety Signal Identified.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- VP Biological Sciences, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00762957
- Sponsor's protocol ID
- 01-04-TL-559-029
- Other IDs
- U1111-1128-4945
- Status last verified
- Feb 2012
- First submitted
- 26 Sep 2008
- Last updated
- 28 Feb 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00762957
- Acronym / sponsor ID
- 01-04-TL-559-029
- Conditions
- Diabetes Mellitus
- Keywords
- Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Drug Therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Hepatic Safety Signal Identified.
- Enrolment
- 15 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Nov 2004
- Primary completion
- Dec 2004 (actual)
- Study completion
- Dec 2004 (actual)
- First posted
- 30 Sep 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| TAK-559 16 mg QD + Metformin QD | Experimental | Drug: TAK-559 and metformin |
| TAK-559 32 mg QD + Metformin QD | Experimental | Drug: TAK-559 and metformin |
| Metformin QD | Active comparator | Drug: Metformin |
Who may qualify
- Ages
- 25 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (28 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TAK-559 and metforminTAK-559 16 mg, tablets, orally, once daily and metformin stable dose orally, once daily for up to 26 weeks. | Drug | TAK-559 16 mg QD + Metformin QD |
| TAK-559 and metforminTAK-559 32 mg, tablets, orally, once daily and metformin stable dose, orally, once daily for up to 26 weeks. | Drug | TAK-559 32 mg QD + Metformin QD |
| MetforminTAK-559 placebo-matching tablets, orally, once daily and metformin stable dose, orally, once daily for up to 26 weeks. | Drug | Metformin QD |
Primary outcome
Change from baseline in glycosylated hemoglobin.
Time frame: Final Visit.
16 secondary outcomes
Change from baseline in glycosylated hemoglobin.
Time frame: Weeks 2, 4, 8, 12, 16 and 20
Change from baseline in fasting plasma glucose.
Time frame: Weeks 2, 4, 8, 12, 16, 20 and Final Visit
Change from baseline in serum insulin.
Time frame: Weeks 4, 12, 16, 20 and Final Visit.
Change from baseline in C-peptide.
Time frame: Weeks 4, 12, 16, 20 and Final Visit.
Change from baseline in triglycerides.
Time frame: Weeks 12, 16, 20 and Final Visit.
Change from baseline in total cholesterol.
Time frame: Weeks 12, 16, 20 and Final Visit.
Change from baseline in high-density lipoprotein.
Time frame: Weeks 12, 16, 20 and Final Visit.
Change from baseline in low-density lipoprotein.
Time frame: Weeks 12, 16, 20 and Final Visit.
Change from baseline in very-low-density lipoprotein.
Time frame: Weeks 12, 16, 20 and Final Visit.
Change from baseline in apolipoproteins A1 and B 100.
Time frame: Final Visit
Change from baseline in free fatty acids.
Time frame: Weeks 12, 16, 20 and Final Visit.
Change from baseline in thrombosis marker plasminogen activator inhibitor-1
Time frame: Weeks 4, 12, 16, 20 and Final Visit
Change from baseline in thrombosis marker fibrinogen.
Time frame: Weeks 4, 12, 16, 20 and Final Visit
Change from baseline in inflammation marker Interleukin-6.
Time frame: Weeks 4, 12, 16, 20 and Final Visit
Change from baseline in inflammation marker C-reactive protein.
Time frame: Weeks 4, 12, 16, 20 and Final Visit
Change from baseline in urinary albumin to creatinine ratio.
Time frame: Weeks 12, 16, 20 and Final Visit
Results and safety
The study was stopped early (reason given: Hepatic Safety Signal Identified.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
VP Biological Sciences study director
Takeda
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing TAK-559 and metformin and Metformin in people with Diabetes Mellitus, run by Takeda.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Hepatic Safety Signal Identified.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in glycosylated hemoglobin. (time frame: Final Visit.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2012.