Diabetes MellitusPhase 3NCT00762190
Study of TAK-559 in Treating Subjects With Type 2 Diabetes Mellitus
A Phase 3 study testing TAK-559 and insulin and Insulin in people with Diabetes Mellitus, run by Takeda.
Trial summary
The purpose of this study was to determine the safety of TAK-559, once daily (QD), in treating subjects receiving a stable dose of insulin to control type 2 diabetes mellitus. Read more about this study
- Who is it for?
- Ages 25 to 65 years
- Conditions the study is for
- Diabetes Mellitus
- What is being tested?
- TAK-559 and insulin and Insulin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 348 participants
- Where
- No sites listed yet
- Study dates
- Nov 2003to 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Had type 2 diabetes mellitus using American Diabetes Association diagnostic criteria, currently treated with insulin therapy.
- Required sponsor approval if older than 65 years.
- Had a Screening glycosylated hemoglobin less than or equal to 8.0%.
- Had a Screening fasting plasma glucose less than or equal to 200 mg/dL (11.1 mmol/L).
- Had a Screening low density lipoprotein less than or equal to 160 mg/dL (4.1 mmol/L).
- Had a Screening thyroid stimulating hormone level less than or equal to 5.5 μU/mL (5.5 μU/L) and greater than or equal to 0.35 μU/mL (0.35 μU/L).
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- Was willing to continue dietary counseling during study and had dietary advice greater than or equal to 2.5 months prior to Screening.
- Had a Screening ejection fraction greater than or equal to 40% from echocardiogram.
- Had a Screening blood pressure less than or equal to 140/95 mm Hg.
- Was willing to perform daily self-monitoring blood glucose tests.
- A female subject of childbearing potential who was sexually active agreed to use adequate contraception, and was neither pregnant nor lactating from Screening throughout the duration of the study.
- Was in good health as determined by physician (via medical history and physical examination) other than having type 2 diabetes mellitus.
- Had clinical laboratory evaluations within normal reference range or deemed not clinically significant by the investigator or sponsor.
- Started insulin therapy at least 3 months prior to Randomization.
Who cannot join
- Had a hypersensitivity to peroxisome proliferator-activated receptor -alpha or gamma agonists, thiazolidinediones, or fibrates.
- Was diagnosed with type 1 diabetes mellitus or hemochromatosis, or had a history of ketoacidosis.
- Required greater than 2 hypertension medications to achieve adequate blood pressure control.
- Had a history of coronary angioplasty or bypass graft, or unstable angina pectoris within 1 year of Screening.
- Had a history of myocardial infarction.
- Had a history of transient ischemic attack or documented cerebrovascular accident within 6 months of Screening.
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- Abdominal, thoracic, or vascular surgery within 6 months of Screening warranting exclusion (investigator's opinion).
- Had a screening creatine phosphokinase value greater than 3 times the upper limit of normal.
- Had persistent unexplained microscopic or macroscopic hematuria or history of bladder cancer.
- Had a screening triglyceride level greater than 500 mg/dL (5.6 mmol/L).
- Experienced a change in allowed lipid-lowering medication (dose or drug) within 2 months of Randomization.
- Experienced a change in blood pressure medication (dose or drug) within 1 month of Randomization.
- Had systemic corticosteroids within 1 month of Randomization.
- Had donated or received blood products within 3 months of Randomization.
- Had a condition known to invalidate glycosylated hemoglobin.
- Had a history of drug abuse or alcohol abuse within 2 years.
- Had a significant cardiovascular disease, including New York Heart Association Functional (Cardiac) Classification II, III or IV.
- Had a Screening B-Type Natriuretic Peptide greater than 100 pg/mL (100 ng/L).
- Had a history of left ventricular hypertrophy (women greater than 110 g/m2 and men greater than 134 g/m2).
- Had a clinically significant mitral insufficiency at Screening.
- Had a clinically significant aortic stenosis at Screening.
- Had a Screening body mass index greater than 45.
- Had a history of cancer with no remission within 5 years of Randomization, other than basal cell or stage 1 squamous cell carcinoma of the skin.
- Had an alanine transaminase or aspartate transaminase level greater than 3 times the upper limit of normal, active liver disease or jaundice at Screening.
- Had a positive human immunodeficiency virus, hepatitis B surface antigen, or hepatitis B e antigen test at Screening.
- Was required to take or intended to continue taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication that may interfered with the evaluation of the study medication, including:
- oral antidiabetic agents (including sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, peroxisome proliferator-activated receptor agonists and metformin)
- fibrates
- systemic corticosteroids
- warfarin
- rifampin
- nicotinic acid
- minoxidil
- hydralazine
- St. John's Wort
- Was participating or had participated in an investigational study within the past 30 days.
- Had a serious disease or condition at Screening or Randomization that could affect life expectancy or made it difficult to manage/follow patient according to protocol.
About this study
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
The purpose of this study was to determine the safety of TAK-559, once daily (QD), in treating subjects receiving a stable dose of insulin to control 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 of TAK-559 in the treatment of patients with type 2 diabetes mellitus who were on a stable dose of insulin.
- Conditions
- Diabetes Mellitus
- Being tested
- TAK-559 and insulin, Insulin
- 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 insulinDrug
TAK-559 32 mg, tablets, orally, once daily and insulin stable dose injection for up to 54 weeks.
InsulinDrug
TAK-559 placebo-matching, tablets, orally, once daily and insulin stable dose injection for up to 54 weeks.
| Study group | Role | What they receive |
|---|---|---|
| TAK-559 32 mg QD + Insulin | Experimental | Not described Receives: Drug: TAK-559 and insulin |
| Insulin | Active comparator | Not described Receives: Drug: Insulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse events.
Measured: All visits or at occurrence.
Clinical safety lab tests.
Measured: Weeks 12, 24, and Final Visit.
12-lead electrocardiogram.
Measured: Weeks: 24 and Final Visit.
Urinalysis.
Measured: Weeks: 12, 24, 36, 48 and Final Visit.
Change from Baseline in Blood pressure and pulse.
Measured: At all visits.
Change from Baseline in Body weight.
Measured: At all visits.
Left ventricular mass index by body surface area measured by echocardiogram.
Measured: Weeks: 24 and Final Visit.
Secondary outcomes (9)
Change from Baseline in total daily dose of insulin.
Measured: At all visits.
Change from Baseline in triglycerides.
Measured: Weeks: 24 and Final Visit.
Change from Baseline in cholesterol.
Measured: Weeks 24 and Final Visit
Change from Baseline in total, high-density lipoproteins.
Measured: Weeks: 24 and Final Visit.
Change from Baseline in low-density lipoproteins.
Measured: Weeks 24 and Final Visit
Change from Baseline in low-density lipoprotein fractionation.
Measured: Weeks 24 and Final Visit
Change from Baseline in very low-density lipoprotein.
Measured: Weeks 24 and Final Visit
Change from Baseline in free fatty acids.
Measured: Weeks 24 and Final Visit
Change from Baseline in apolipoproteins (AI, B).
Measured: Weeks 24 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 2003
- 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
- 348 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
- NCT00762190
- Sponsor's protocol ID
- 01-03-TL-559-016
- Other IDs
- U1111-1128-1034
- Status last verified
- Nov 2012
- First submitted
- 26 Sep 2008
- Last updated
- 12 Nov 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00762190
- Acronym / sponsor ID
- 01-03-TL-559-016
- 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
- 348 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Nov 2003
- 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 was to determine the safety of TAK-559, once daily (QD), in treating subjects receiving a stable dose of insulin to control 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 of TAK-559 in the treatment of patients with type 2 diabetes mellitus who were on a stable dose of insulin.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TAK-559 32 mg QD + Insulin | Experimental | Drug: TAK-559 and insulin |
| Insulin | Active comparator | Drug: Insulin |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Had type 2 diabetes mellitus using American Diabetes Association diagnostic criteria, currently treated with insulin therapy.
- Required sponsor approval if older than 65 years.
- Had a Screening glycosylated hemoglobin less than or equal to 8.0%.
- Had a Screening fasting plasma glucose less than or equal to 200 mg/dL (11.1 mmol/L).
- Had a Screening low density lipoprotein less than or equal to 160 mg/dL (4.1 mmol/L).
Key exclusion criteria (37 listed)
- Had a hypersensitivity to peroxisome proliferator-activated receptor -alpha or gamma agonists, thiazolidinediones, or fibrates.
- Was diagnosed with type 1 diabetes mellitus or hemochromatosis, or had a history of ketoacidosis.
- Required greater than 2 hypertension medications to achieve adequate blood pressure control.
- Had a history of coronary angioplasty or bypass graft, or unstable angina pectoris within 1 year of Screening.
- Had a history of myocardial infarction.
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 insulinTAK-559 32 mg, tablets, orally, once daily and insulin stable dose injection for up to 54 weeks. | Drug | TAK-559 32 mg QD + Insulin |
| InsulinTAK-559 placebo-matching, tablets, orally, once daily and insulin stable dose injection for up to 54 weeks. | Drug | Insulin |
Primary outcome
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.
9 secondary outcomes
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
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 12 Nov 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 insulin and Insulin 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 37 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 12 Nov 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?
Incidence of Adverse events. (time frame: All visits or at occurrence.). The study lists 7 primary outcomes in all. 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 12 Nov 2012.