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Pioglitazone

Phase 3

Diabetes Mellitus | Small molecule | Metabolic |Takeda Pharmaceutical Company Limited|Last Updated: Apr 27, 2020

Target and mechanism

ModalitySmall molecule

Also known as Pioglitazone and insulin, Pioglitazone and azilsartan, Pioglitazone and atorvastatin, Pioglitazone and Metformin, Pioglitazone and metformin, Pioglitazone and Glimepiride

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials12
Total Enrollment8,584

FDA Designations

No designations recorded

Clinical trial landscape

Pioglitazone · 20 trials · 17 indications

Phase 3 11Phase 2 8Phase 1 1
NCT00091949Insulin Resistance Intervention After Stroke TrialStroke
COMPLETED3,876 Analytics
NCT01156597Effects of Pioglitazone on High-density Lipoprotein (HDL) Function in Persons With DiabetesType 2 Diabetes Mellitus
COMPLETED30 Analytics
NCT00727857Efficacy and Safety of Pioglitazone and Metformin Combination Therapy in Treating Type 2 Diabetes Mellitus.Diabetes Mellitus
COMPLETED600 Analytics
NCT00770653Efficacy of Pioglitazone/Metformin Combination Therapy in Subjects With Type 2 Diabetes Mellitus and Dyslipidemia.Diabetes Mellitus
COMPLETED305 Analytics
NCT00772174Efficacy and Safety Study of Pioglitazone Combined With Metformin on Metabolic Syndrome in Subjects With Type 2 DiabetesDiabetes Mellitus
COMPLETED418 Analytics
NCT00770952Efficacy of Pioglitazone and Glimepiride Combination Therapy in Treating Subjects With Type 2 Diabetes Mellitus.Diabetes Mellitus
COMPLETED91 Analytics
NCT00225264Efficacy Study of Pioglitazone and Glimepiride on the Rate of Progression of Atherosclerotic Disease.Diabetes Mellitus
COMPLETED458 Analytics
NCT00225277Efficacy Study of Pioglitazone Compared to Glimepiride on Coronary Atherosclerotic Disease Progression in Subjects With Type 2 Diabetes MellitusDiabetes Mellitus
COMPLETED547 Analytics
NCT00174993Efficacy of Pioglitazone on Macrovascular Outcome in Patients With Type 2 DiabetesDiabetes Mellitus
COMPLETED4,373 Analytics
NCT00521742Efficacy of Pioglitazone Compared to Glyburide in Treating Subjects With Type 2 Diabetes Mellitus and Mild Cardiac DiseaseDiabetes Mellitus
COMPLETED300 Analytics
PHASE3COMPLETED
Insulin Resistance Intervention After Stroke Trial
StrokeUnlock trial analytics
PHASE3COMPLETED
Effects of Pioglitazone on High-density Lipoprotein (HDL) Function in Persons With Diabetes
Type 2 Diabetes MellitusUnlock trial analytics
PHASE3COMPLETED
Efficacy and Safety of Pioglitazone and Metformin Combination Therapy in Treating Type 2 Diabetes Mellitus.
Diabetes MellitusUnlock trial analytics
PHASE3COMPLETED
Efficacy of Pioglitazone/Metformin Combination Therapy in Subjects With Type 2 Diabetes Mellitus and Dyslipidemia.
Diabetes MellitusUnlock trial analytics
PHASE3COMPLETED
Efficacy and Safety Study of Pioglitazone Combined With Metformin on Metabolic Syndrome in Subjects With Type 2 Diabetes
Diabetes MellitusUnlock trial analytics
PHASE3COMPLETED
Efficacy of Pioglitazone and Glimepiride Combination Therapy in Treating Subjects With Type 2 Diabetes Mellitus.
Diabetes MellitusUnlock trial analytics
PHASE3COMPLETED
Efficacy Study of Pioglitazone and Glimepiride on the Rate of Progression of Atherosclerotic Disease.
Diabetes MellitusUnlock trial analytics
PHASE3COMPLETED
Efficacy Study of Pioglitazone Compared to Glimepiride on Coronary Atherosclerotic Disease Progression in Subjects With Type 2 Diabetes Mellitus
Diabetes MellitusUnlock trial analytics
PHASE3COMPLETED
Efficacy of Pioglitazone on Macrovascular Outcome in Patients With Type 2 Diabetes
Diabetes MellitusUnlock trial analytics
PHASE3COMPLETED
Efficacy of Pioglitazone Compared to Glyburide in Treating Subjects With Type 2 Diabetes Mellitus and Mild Cardiac Disease
Diabetes MellitusUnlock trial analytics

Study Endpoints

Primary Endpoints

Recurrent Fatal or Non-fatal Stroke, or Fatal or Non-fatal Myocardial Infarction
Up to 5 years
Increased HDL-Cholesterol and Decreased Triglycerides
24 weeks

The primary endpoint will be increased high density lipoprotein cholesterol and decreased triglycerides measured as the difference after 12 or 24 weeks of treatment from baseline levels. The data are expressed as the percent change from the baseline value and calculated using he equation: * Change=\[100%\*(Endpoint value - Baseline Value)/Baseline Value\]

Percent Change From Baseline in Glycosylated Hemoglobin
Baseline and Week 24

The change between the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at final visit or week 24 and Glycosylated Hemoglobin collected at baseline.

The Mean Increase From Baseline in High-Density Lipoprotein Cholesterol.
Baseline and Week 24.

The increase in High-Density Lipoprotein (HDL) Cholesterol collected at week 24 or final visit and HDL-Cholesterol collected at baseline.

Increase in High-Density Lipoprotein cholesterol levels.
Final Visit.
Change from Baseline in Homeostatic Model Assessment - Beta cell.
Week: 24 or Final Visit beyond week 12.
Absolute change from Baseline in carotid intima-media thickness.
Weeks 24, 48 and Final Visit.
Nominal Change From Baseline in Percent Atheroma Volume
Baseline and Final Visit (up to 72 weeks)

The nominal change from baseline in percent atheroma volume for all slices of anatomically comparable segments of the target coronary artery. Assessment completed at the Week 72 visit or Final Visit if treatment was prematurely discontinued.

Time to the Composite of All Cause Mortality, Non-Fatal Myocardial Infarction, Stroke, Acute Coronary Syndrome, Major Leg Amputation, Cardiac Intervention, Bypass Surgery or Leg Revascularization.
At First Occurrence
Change in the walking distance during a standardized 6-minute walk test.
Weeks 2, 16, 24, 40, and 52 or Final Visit
Change in fasting triglyceride level
Final Visit
Airway Reactivity
12 weeks

Presence and degree of airway hyperresponsiveness assessed by methacholine challenge test. PC20= Methacholine dose at wich the FEV1 deops by \> 20% from pre-methacholine baseline values.

Glucose Tolerance at 24 Weeks
24 weeks

1. Normal = normal plasma glucose and normal glucose tolerance (OGTT). 2. Impaired category includes all non-diabetic participants with either a) Impaired fasting glucose = fasting plasma glucose \>110 mg/dl and \<126 mg/dl; or b) Impaired glucose intolerance = 2-hour plasma glucose (OGTT) \>140 mg/dl and \<200 mg/dl. 3. Diabetes = fasting plasma glucose \>126 mg/dl 2-hour (OGTT) plasma glucose \>200 mg/dl.

Glucose Tolerance at 48 Weeks
48 weeks

1. Normal = normal plasma glucose and normal glucose tolerance (OGTT). 2. Impaired category includes all non-diabetic participants with either a) Impaired fasting glucose = fasting plasma glucose \>110 mg/dl and \<126 mg/dl; or b) Impaired glucose intolerance = 2-hour plasma glucose (OGTT) \>140 mg/dl and \<200 mg/dl. 3. Diabetes = fasting plasma glucose \>126 mg/dl 2-hour (OGTT) plasma glucose \>200 mg/dl.

Insulin Sensitivity Index for Glycemia at 24 Weeks
24 weeks

Insulin Sensitivity = Index for Glycemia (ISI gly) = 2 / (\[INSp x GLYp\] + 1). GLYp = Glycemic 0-2 hr area = sum of normalized (based on institutional values) 0 \& 2 hr glucose. INSp = Insulinemic 0-2 hr area = sum of normalized (based on institutional values) 0 \& 2 hr insulin.

Insulin Sensitivity Index for Glycemia at 48 Weeks.
48 weeks

Insulin Sensitivity = Index for Glycemia (ISI gly) = 2 / (\[INSp x GLYp\] + 1). GLYp = Glycemic 0-2 hr area = sum of normalized (based on institutional values) 0 \& 2 hr glucose. INSp = Insulinemic 0-2 hr area = sum of normalized (based on institutional values) 0 \& 2 hr insulin.

Change of total daily Insulin Dose.
Week 24 or Final Visit.
Change in the high-sensitivity C-reactive Protein value.
Week: 12.
Incidence of Cardiac Troponin I elevation (greater than 1 upper limit of normal) post-percutaneous coronary intervention with stent implantation.
24 hours post stent implantation.
Change in the intima-media thickness of the common carotid artery.
Week 24.
Change from Baseline in glycosylated hemoglobin.
Week 24 or Final Visit
Capillary filtration capacity.
Final Visit
Change from Baseline in BOLD fMRI Signal Related to Pioglitazone in Regions of the Brain Related to Cognition.
Baseline, Day 7 and Day 14.

Regions of the brain related to cognition include the hippocampus and the dorsolateral prefrontal cortex.

Secondary Endpoints

Fatal or Non-fatal Stroke Alone
5 years
Acute Coronary Syndrome
5 years
Development of Overt Diabetes
5 years
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Study Design & Arms

AllocationRANDOMIZED
MaskingTRIPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
PioglitazoneACTIVE_COMPARATORpioglitazone
PlaceboPLACEBO_COMPARATORinactive substance
Pioglitazone GroupACTIVE_COMPARATORThis is a baseline versus treatment study comparing subjects on pioglitazone to a matched group of subjects treated with either metformin or sulfonylurea with the intent of controlling blood sugar to a comparable level
Comparator GroupNO_INTERVENTIONThis group of subjects will be maintained on standard treatment with either metformin or sulfonylurea with the intent of controlling blood sugar to a comparable level as group treated with pioglitazone.
Pioglitazone 15 mg /Metformin 850 mg BIDEXPERIMENTAL -
Pioglitazone 15 mg BIDACTIVE_COMPARATOR -
Metformin 850 mg BIDACTIVE_COMPARATOR -
Pioglitazone 15 mg and Metformin 850 mg BIDEXPERIMENTAL -
Glimepiride 2 mg and Metformin 850 mg BIDACTIVE_COMPARATOR -
Pioglitazone + MetforminEXPERIMENTAL -
MetforminACTIVE_COMPARATOR -
Pioglitazone 30 mg to 45 mg QD + Glimepiride 2 mg to 4 mg QDEXPERIMENTAL -
Glimepiride 4 mg to 6 mg QDACTIVE_COMPARATOR -
Pioglitazone QDEXPERIMENTAL -
Glimepiride QDACTIVE_COMPARATOR -
Placebo QDPLACEBO_COMPARATOR -
Pioglitazone 15 mg to 45 mg QDEXPERIMENTAL -
Glyburide 2.5 mg to 15 mg, QDACTIVE_COMPARATOR -
Pioglitazone 15 mg or 30 mg QDEXPERIMENTAL -
Glyburide 5 mg or 10 mg, QDACTIVE_COMPARATOR -
Rosiglitazone QDACTIVE_COMPARATOR -
1ACTIVE_COMPARATOR -
2PLACEBO_COMPARATOR -
sugar pill (placebo)PLACEBO_COMPARATOR1 sugar pill (placebo) taken once daily for 48 weeks.
Pioglitazone 30mg QDEXPERIMENTAL(and variable insulin therapy)
Pioglitazone 15 mg to 30 mg QDEXPERIMENTAL -
Pioglitazone 15 mg to 30 mg QD + Ramipril 2.5 mg to 5 mg QDACTIVE_COMPARATOR -
Ramipril 2.5 mg to 5 mg QDACTIVE_COMPARATOR -
Pioglitazone 30 mg to 45 mg QDEXPERIMENTAL -
Pioglitazone 30mg to 45 mg QD + Atorvastatin 20 mg to 40 mg QDEXPERIMENTAL -
Atorvastatin 20mg to 40 mg QDACTIVE_COMPARATOR -
Pioglitazone 15 mg QD + Azilsartan 5 mg QDEXPERIMENTAL -
Pioglitazone 15 mg QD + Azilsartan 40 mg QDEXPERIMENTAL -
Pioglitazone 15 mg QDACTIVE_COMPARATOR -
Pioglitazone 45 mg QD + Azilsartan 5 mg QDEXPERIMENTAL -
Pioglitazone 45 mg QD + Azilsartan 40 mg QDEXPERIMENTAL -
Pioglitazone 45 mg QDACTIVE_COMPARATOR -
Pioglitazone (Dose 1) QDEXPERIMENTAL -
Pioglitazone (Dose 2) QDEXPERIMENTAL -
Pioglitazone (Dose 3) QDEXPERIMENTAL -

Interventions

NameTypeDescription
pioglitazoneDRUGa thiazolidinedione drug
placeboDRUGan inactive substance
Pioglitazone and metforminDRUGPioglitazone 15 mg /metformin 850 mg combination, tablets, orally, twice daily for up to 24 weeks.
MetforminDRUGMetformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Glimepiride and MetforminDRUGPioglitazone/metformin placebo-matching combination tablets, orally, twice daily and glimepiride 2 mg, tablets, orally, once daily and metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.
Pioglitazone and GlimepirideDRUGPioglitazone 30 mg, tablets, orally, once daily and Glimepiride 2 mg, tablets, orally once daily for two weeks; increased to: Pioglitazone 30 mg, tablets, orally, once daily and Glimepiride 4 mg, tablets, orally, once daily for two weeks; increased to: Pioglitazone 45 mg, tablets, orally, once daily and Glimepiride 4 mg, orally, once daily for up to 20 weeks.
GlimepirideDRUGPioglitazone placebo-matching tablets, orally, once daily and Glimepiride 4 mg, tablets, orally once daily for two weeks; increased to: Pioglitazone placebo-matching tablets, orally, once daily and Glimepiride 5 mg, tablets, orally once daily for two weeks; increased to: Pioglitazone placebo-matching tablets, orally, once daily and Glimepiride 6 mg, tablets, orally once daily for up to 20 weeks.
GlyburideDRUGGlyburide 2.5 mg to 15 mg, capsules, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 52 weeks.
RosiglitazoneDRUGRosiglitazone 4 mg capsules, orally, once daily and placebo-matching capsules, orally, once daily for up to 12 weeks; increasing to rosiglitazone 4 mg, capsules, orally, twice daily for up to 12 weeks
Pioglitazone and insulinDRUGPioglitazone 30 mg, tablets, orally, once daily and variable insulin therapy for up to 24 weeks.
InsulinDRUGPioglitazone placebo-matching tablets, orally, once daily and variable insulin therapy for up to 24 weeks.
Pioglitazone and ramiprilDRUGPioglitazone 15 mg, tablets, orally, once daily and ramipril 2.5 mg, tablets, orally, once daily for two weeks; increased to: Pioglitazone 30 mg, tablets, orally, once daily and ramipril 5 mg, tablets, orally, once daily for up to 10 weeks.
RamiprilDRUGPioglitazone placebo-matching tablets, orally, once daily and ramipril 2.5 mg, tablets, orally, once daily for two weeks; increased to: Pioglitazone placebo-matching tablets, orally, once daily and ramipril 5 mg, tablets, orally, once daily for up to 10 weeks.
Pioglitazone and atorvastatinDRUGPioglitazone 30 mg, capsules, orally, once daily and atorvastatin 20 mg, tablets, orally, once daily for 4 weeks; increase to: Pioglitazone 45 mg, capsules, orally, once daily and atorvastatin 40 mg, tablets, orally, once daily for up to 20 weeks.
AtorvastatinDRUGPioglitazone placebo-matching capsules, orally, once daily and atorvastatin 20 mg, tablets, orally, once daily for 4 weeks; increased to Pioglitazone placebo-matching capsules, orally, once daily and atorvastatin 40 mg, tablets, orally, once daily for up to 20 weeks.
Pioglitazone and azilsartanDRUGPioglitazone 15 mg, tablets, orally, once daily and azilsartan 5 mg, tablets, orally, once daily for up to 24 weeks.
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Eligibility Criteria

Age Range40 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites183

Inclusion Criteria 1. Ages 40 years or greater at the time of randomization. 2. Ischemic stroke or TIA no less than 14 days and no more than 6 months before randomization 3. Documentation of insulin resistance as defined by a value over 3.0 on the Homeostasis Model Assessment of insulin sensitivity...

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