Diabetes MellitusPhase 3NCT00762112
Safety Study of TAK-559 in Treating Subjects With Type 2 Diabetes Mellitus
A Phase 3 study testing TAK-559 in people with Diabetes Mellitus, run by Takeda.
Trial summary
The purpose of this study was to determine the long-term safety of TAK-559, once daily (QD), in subjects with Type 2 Diabetes. Read more about this study
- Who is it for?
- Ages 25 to 80 years
- Conditions the study is for
- Diabetes Mellitus
- What is being tested?
- TAK-559
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 316 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Required sponsor approval if older than 80 years.
- Had either:
- Successfully completed Protocol 01-03-TL-559-016, or
- Participated in either Protocol 01-02-TL-559-013, 01-02-TL-559-014, 01-04-TL-559-028, or 01-04-TL-559-029 and either
- completed the study
- prematurely terminated from the study due to the HbA1c withdrawal criterion after at least 12 weeks of treatment, or
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- in the opinion of the investigator, demonstrated a lack of efficacy after at least 16 weeks of treatment and was withdrawn from the study.
- 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.
- Were willing to continue following an individualized weight maintenance diet during the study period.
- Had evidence of insulin secretory capacity, as demonstrated by a fasting C-peptide concentration of greater than or equal to 1.5 ng/mL (0.50 nmol/L) at the prior visit of Protocol 013, 014, 016, 028, or 029.
- Were willing to perform daily self-monitoring blood glucose tests.
- Were in good health at Enrollment, as determined by a physician at the final visit of Protocol 013, 014, 016, 028, or 029 (ie, via medical history and physical examination), other than having type 2 diabetes mellitus and New York Heart Association Classification I or II congestive heart failure.
- Had clinical laboratory evaluations (including clinical chemistry, hematology, and complete urinalysis after fasting for at least 8 hours) within the normal reference range for the testing laboratory, unless the results were deemed not clinically significant by the investigator or sponsor, at the prior visit of Protocol 013, 014, 016, 028, or 029.
- 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 the prior visit of Protocol 013, 014, 016, 028, or 029.
Who cannot join
- Had significant cardiovascular disease, including, but not limited to, New York Heart Association Classification III or IV CHF at Enrollment.
- Had a planned surgical or catheter intervention for coronary angioplasty within 12 months after the Enrollment Visit.
- Had a systolic blood pressure greater than 140 mm Hg or a diastolic blood pressure greater than 95 mm Hg at Enrollment.
- Had symptomatic orthostatic hypotension or systolic blood pressure less than 90 mm Hg at Enrollment.
- Had a history of a clinically significant abnormal electrocardiogram or experienced any cardiovascular event including, but not limited to, myocardial infarction, coronary angioplasty or bypass graft, unstable angina pectoris, transient ischemic attacks, or documented cerebrovascular accident during Protocol 013, 014, 016, 028, or 029.
- Had a creatine phosphokinase value above 3 times the upper limit of normal at the prior visit of Protocol 013, 014, 016, 028, or 029.
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- Had a triglyceride level greater than 500 mg/dL (5.6 nmol/L) at the prior visit of Protocol 013, 014, 016, 028, or 029.
- Had an alanine aminotransferase or aspartate aminotransferase level above 3 times the upper limit of normal, active liver disease, or jaundice at any time during Protocol 013, 014, 016, 028, or 029.
- Had donated and/or received any blood products within 3 months prior to Enrollment.
- Had used illicit drugs or abused alcohol during participation in Protocol 013, 014, 016, 028, or 029.
- Had experienced another illness occurring at the same time requiring hospitalization during the occurring at the same time 3 weeks before the Enrollment Visit.
- Had experienced any other serious disease or condition during participation in Protocol 013, 014, 016, 028, or 029 that might have affected life expectancy or made it difficult to successfully manage and follow the patient according to the protocol.
- 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:
- insulin (for patients who participated in Protocol 01-02-TL-559-013, 01-02-TL-559-014, 01-04-TL-559-028, and 01-04-TL-559-029)
- prescription-strength niacin
- fibric acid derivatives
- systemic corticosteroids
- warfarin
- rifampin
- nicotinic acid
- St. John's Wort
- thiazolidinediones
- peroxisome proliferator-activated receptor agonists other than the study drug.
- Had experienced persistent unexplained microscopic or macroscopic hematuria or developed cancer of the bladder while participating in Protocol 013, 014, 016, 028, or 029.
About this study
Official title: A Long-Term, Open-Label, Phase 3a Safety Study of Oral TAK-559 (32 mg QD) in the Treatment of Patients With Type 2 Diabetes Mellitus
The purpose of this study was to determine the long-term safety of TAK-559, once daily (QD), in subjects with Type 2 Diabetes.
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.
- Conditions
- Diabetes Mellitus
- Being tested
- TAK-559
- 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-559Drug
TAK-559 32 mg, tablets, orally, once daily for up to 24 months.
| Study group | Role | What they receive |
|---|---|---|
| TAK-559 32 mg QD | Experimental | Not described Receives: Drug: TAK-559 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in clinical laboratory hematology tests.
Measured: Week 2 and Months 6, 12, 18, and Final Visit
Change from baseline in clinical laboratory chemistry tests.
Measured: Week 2 and Months 6, 12, 18, and Final Visit
Blood pressure measurements.
Measured: All visits.
Pulse measurements.
Measured: All visits.
Body weight.
Measured: All visits.
Physical examinations.
Measured: Months 6, 12, 18, and Final Visit
12-lead electrocardiogram.
Measured: Months 6, 12, and Final Visit
Adverse event occurrence.
Measured: All visits or at occurrence
Secondary outcomes (21)
Change from baseline in glycosylated hemoglobin.
Measured: Months 3, 6, 9, 12, 15, 18, 21, and Final Visit
Change from baseline in fasting plasma glucose.
Measured: All visits.
Change from baseline in fasting insulin.
Measured: Months 3, 6, 9, 12, 15, 18, 21, and Final Visit
Change from baseline in fasting C-peptide.
Measured: Months 6, 12, 18, and Final Visit
Change from baseline in triglycerides.
Measured: Months 6, 12, 18, and Final Visit
Change from baseline in total cholesterol.
Measured: Months 6, 12, 18, and Final Visit
Change from baseline in high-density lipoprotein.
Measured: Months 6, 12, 18, and Final Visit
Change from baseline in low-density lipoprotein.
Measured: Months 6, 12, 18, and Final Visit
Change from baseline in very-low-density lipoprotein.
Measured: Months 6, 12, 18, and Final Visit
Change from baseline in low-density lipoprotein fractionation.
Measured: Months 6, 12, 18, and Final Visit
Change from baseline in intermediate-density lipoprotein size.
Measured: Months 6, 12, 18, and Final Visit
Change from baseline in large low-density lipoprotein size.
Measured: Months 6, 12, 18, and Final Visit
Change from baseline in small low-density lipoprotein size.
Measured: Months 6, 12, 18, and Final Visit
Change from baseline in medium-small low-density lipoprotein size.
Measured: Months 6, 12, 18, and Final Visit
Change from baseline in very-small low-density lipoprotein size.
Measured: Months 6, 12, 18, and Final Visit
Change from baseline in mean low-density lipoprotein size.
Measured: Months 6, 12, 18, and Final Visit
Change from baseline in apolipoproteins A1 and B.
Measured: Months 12 and Final Visit
Change from baseline in atherosclerosis marker plasminogen activator inhibitor 1.
Measured: Months 6, 12, and Final Visit
Change from baseline in atherosclerosis marker fibrinogen.
Measured: Months 6, 12, and Final Visit
Change from baseline in inflammation marker Interleukin-6.
Measured: Months 6, 12, and Final Visit
Change from baseline in inflammation marker C-reactive protein.
Measured: Months 6, 12, 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 316 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
- NCT00762112
- Sponsor's protocol ID
- 01-03-TL-559-017
- Other IDs
- U1111-1128-4850
- 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 Long-Term, Open-Label, Phase 3a Safety Study of Oral TAK-559 (32 mg QD) in the Treatment of Patients With Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT00762112
- Acronym / sponsor ID
- 01-03-TL-559-017
- 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
- 316 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 long-term safety of TAK-559, once daily (QD), in subjects with Type 2 Diabetes.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TAK-559 32 mg QD | Experimental | Drug: TAK-559 |
Who may qualify
- Ages
- 25 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Required sponsor approval if older than 80 years.
- Had either:
- 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.
- Were willing to continue following an individualized weight maintenance diet during the study period.
- Had evidence of insulin secretory capacity, as demonstrated by a fasting C-peptide concentration of greater than or equal to 1.5 ng/mL (0.50 nmol/L) at the prior visit of Protocol 013, 014, 016, 028, or 029.
Key exclusion criteria (24 listed)
- Had significant cardiovascular disease, including, but not limited to, New York Heart Association Classification III or IV CHF at Enrollment.
- Had a planned surgical or catheter intervention for coronary angioplasty within 12 months after the Enrollment Visit.
- Had a systolic blood pressure greater than 140 mm Hg or a diastolic blood pressure greater than 95 mm Hg at Enrollment.
- Had symptomatic orthostatic hypotension or systolic blood pressure less than 90 mm Hg at Enrollment.
- Had a history of a clinically significant abnormal electrocardiogram or experienced any cardiovascular event including, but not limited to, myocardial infarction, coronary angioplasty or bypass graft, unstable angina pectoris, transient ischemic attacks, or documented cerebrovascular accident during Protocol 013, 014, 016, 028, or 029.
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-559TAK-559 32 mg, tablets, orally, once daily for up to 24 months. | Drug | TAK-559 32 mg QD |
Primary outcome
Change from baseline in clinical laboratory hematology tests.
Time frame: Week 2 and Months 6, 12, 18, and Final Visit
Change from baseline in clinical laboratory chemistry tests.
Time frame: Week 2 and Months 6, 12, 18, and Final Visit
Blood pressure measurements.
Time frame: All visits.
Pulse measurements.
Time frame: All visits.
Body weight.
Time frame: All visits.
Physical examinations.
Time frame: Months 6, 12, 18, and Final Visit
12-lead electrocardiogram.
Time frame: Months 6, 12, and Final Visit
Adverse event occurrence.
Time frame: All visits or at occurrence
21 secondary outcomes
Change from baseline in glycosylated hemoglobin.
Time frame: Months 3, 6, 9, 12, 15, 18, 21, and Final Visit
Change from baseline in fasting plasma glucose.
Time frame: All visits.
Change from baseline in fasting insulin.
Time frame: Months 3, 6, 9, 12, 15, 18, 21, and Final Visit
Change from baseline in fasting C-peptide.
Time frame: Months 6, 12, 18, and Final Visit
Change from baseline in triglycerides.
Time frame: Months 6, 12, 18, and Final Visit
Change from baseline in total cholesterol.
Time frame: Months 6, 12, 18, and Final Visit
Change from baseline in high-density lipoprotein.
Time frame: Months 6, 12, 18, and Final Visit
Change from baseline in low-density lipoprotein.
Time frame: Months 6, 12, 18, and Final Visit
Change from baseline in very-low-density lipoprotein.
Time frame: Months 6, 12, 18, and Final Visit
Change from baseline in low-density lipoprotein fractionation.
Time frame: Months 6, 12, 18, and Final Visit
Change from baseline in intermediate-density lipoprotein size.
Time frame: Months 6, 12, 18, and Final Visit
Change from baseline in large low-density lipoprotein size.
Time frame: Months 6, 12, 18, and Final Visit
Change from baseline in small low-density lipoprotein size.
Time frame: Months 6, 12, 18, and Final Visit
Change from baseline in medium-small low-density lipoprotein size.
Time frame: Months 6, 12, 18, and Final Visit
Change from baseline in very-small low-density lipoprotein size.
Time frame: Months 6, 12, 18, and Final Visit
Change from baseline in mean low-density lipoprotein size.
Time frame: Months 6, 12, 18, and Final Visit
Change from baseline in apolipoproteins A1 and B.
Time frame: Months 12 and Final Visit
Change from baseline in atherosclerosis marker plasminogen activator inhibitor 1.
Time frame: Months 6, 12, and Final Visit
Change from baseline in atherosclerosis marker fibrinogen.
Time frame: Months 6, 12, and Final Visit
Change from baseline in inflammation marker Interleukin-6.
Time frame: Months 6, 12, and Final Visit
Change from baseline in inflammation marker C-reactive protein.
Time frame: Months 6, 12, 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 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 24 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?
Change from baseline in clinical laboratory hematology tests. (time frame: Week 2 and Months 6, 12, 18, and Final Visit). The study lists 8 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.