Diabetes MellitusPhase 3PRISMANCT00772174
Efficacy and Safety Study of Pioglitazone Combined With Metformin on Metabolic Syndrome in Subjects With Type 2 Diabetes
A Phase 3 study testing Pioglitazone and Metformin and Metformin in people with Diabetes Mellitus, run by Takeda.
Trial summary
The purpose of this study was to determine the efficacy of pioglitazone taken with metformin on high-density lipoprotein cholesterol in subjects with Type 2 Diabetes. Read more about this study
- Who is it for?
- Ages 35 to 75 years
- Conditions the study is for
- Diabetes Mellitus
- What is being tested?
- Pioglitazone 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
- 418 participants
- Where
- No sites listed yet
- Study dates
- Jan 2007to Feb 2008
- 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 35 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of Type 2 Diabetes Mellitus.
- Has glycosylated hemoglobin levels between 6.0% and 8.0%.
- Treatment with metformin (2,000 to 3,000 mg daily) for at least 3 months.
- Has reduced high-density lipoprotein cholesterol levels less than 40 mg/dl in males and less than 50 mg/dl in females, irrespective of treatment with statins.
- Has central obesity defined as a waist circumference greater than or equal to 94 cm for men and greater than or equal to 80 cm for females.
- Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
Who cannot join
- Has a diagnosis of Type 1 Diabetes Mellitus.
- 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:
- other oral antidiabetic drugs than metformin or with insulin in the 3 months preceding study entry.
- Fibrates
- Rifampicin
- Has any disease with malabsorption.
Show all 17Show fewer
- Has acute or chronic pancreatitis.
- Has familial polyposis coli.
- Has a medical history of myocardial infarction, transient ischemic attacks or stroke in the past 6 months.
- Has heart failure as defined by the New York Heart Association classification I-IV.
- Has significant liver impairment, with an alanine aminotransferase level greater than 2.5 the upper limit of normal range.
- Has significant renal impairment, with a serum creatinine level greater than 1.5 mg/dl for men and greater than 1.2 mg/dl for women.
- Has anemia of any etiology (defined as hemoglobin levels less than 10.5 g/dL) or any other hematologic disease.
- Has a diagnosis or suspicion of neoplastic disease.
- History of chronic alcohol or drug abuse.
- Known allergy, sensitivity or intolerance to the study drugs and their formulation ingredients.
- Participation in another trial in the 3 months preceding study entry.
About this study
Official title: Double-blind, Randomized, Multicenter, Parallel-Group Study to Evaluate the Effects of Pioglitazone on Metabolic Syndrome in Patients With Type 2 Diabetes Treated With Metformin
The purpose of this study was to determine the efficacy of pioglitazone taken with metformin on high-density lipoprotein cholesterol in subjects with Type 2 Diabetes.
Read the detailed description
Diabetes is none of the most common, chronic diseases worldwide and affects nearly 200 million people. It is the fourth or fifth leading cause of death in developed countries, and it is expected that diabetes will reach epidemic proportions, affecting 333 million people globally by 2025.
The metabolic syndrome is a cluster of the most dangerous cardiovascular risk factors and includes diabetes and pre-diabetes in addition to abdominal obesity, low high-density lipoprotein cholesterol, high triglycerides and hypertension. It is estimated that around a quarter of the world's adult population has metabolic syndrome, and are twice as likely to die and three times as likely to have a heart attack or stroke when compared to people without the syndrome. In addition, non-diabetic people with metabolic syndrome have a fivefold greater risk of developing type 2 diabetes. The clustering of cardiovascular risk factors that typifies the metabolic syndrome is now considered the driving force for a cardiovascular disease epidemic.
Metabolic syndrome has been recently defined by a Consensus Conference of the International Diabetes Federation as a cluster of clinical and laboratory signs characterized by the presence of abnormal deposition of fat tissue in the abdomen and visceral districts, and at least two other clinical and laboratory abnormalities, including altered glucose metabolism or type 2 diabetes and decreased levels of high-density lipoprotein cholesterol. One of the underlying pathophysiological mechanisms of metabolic syndrome is insulin resistance, characterized by an increased glucose output from the liver, and reduced glucose uptake in the muscle and adipose tissue cells. Drugs whose mechanism of action consists of increasing insulin sensitivity in the target tissues are able to reduce the clinical manifestations and consequences of metabolic syndrome.
While each individual component of metabolic syndrome confers an increased risk of cardiovascular-related complications or death, this risk is more pronounced when the syndrome itself is present. The more components of metabolic syndrome are evident, the higher is the cardiovascular mortality rate.
- Conditions
- Diabetes Mellitus
- Being tested
- Pioglitazone 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.
Pioglitazone and MetforminDrug
Also called ACTOS®, AD4833
Pioglitazone 15 mg, tablets, orally, two-times daily and metformin stable dose, orally, three-times daily for 4 weeks; then increased to pioglitazone 15 mg, tablets, orally, three-times daily and metformin stable dose, orally, three-times daily for up to 20 weeks.
MetforminDrug
Pioglitazone placebo-matching tablets, orally, two-times daily and metformin stable dose, orally, three-times daily for 4 weeks; then increased to pioglitazone placebo-matching tablets, orally, three-times daily and metformin stable dose, orally, three-times daily for up to 20 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone + Metformin | Experimental | Not described Receives: Drug: Pioglitazone and Metformin |
| Metformin | Active comparator | Not described Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Increase in High-Density Lipoprotein cholesterol levels.
Measured: Final Visit.
Secondary outcomes (5)
The change from Baseline in Metabolic Syndrome, as defined by the International Diabetes Federation (aggregate waist circumference, fasting plasma glucose, triglycerides and high-density lipoprotein cholesterol).
Measured: Weeks: 8 and 24.
The change from Baseline in Metabolic Syndrome, as defined by the International Diabetes Federation (blood pressure).
Measured: At all Visits.
The change from Baseline in Individual Metabolic Parameters (insulin sensitivity and beta-cell function, inflammatory cytokines, adipokines, endothelial functionality).
Measured: Weeks: 8 and 24.
Adverse Events.
Measured: At all Visits.
The change from Baseline in Laboratory Parameters (hematology, chemistry and urinalysis).
Measured: Weeks: 8 and 24.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2008 (estimated)
- Study startJan 2007
- Primary completionFeb 2008
- Study completionFeb 2008
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
- 418 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Medical Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00772174
- Sponsor's protocol ID
- IT-PIO-108
- Other IDs
- 2006-000725-54, PIOc/LAN07/TIF, U1111-1115-9278
- Acronym
- PRISMA
- Status last verified
- Jul 2010
- First submitted
- 8 Oct 2008
- Last updated
- 5 Jul 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double-blind, Randomized, Multicenter, Parallel-Group Study to Evaluate the Effects of Pioglitazone on Metabolic Syndrome in Patients With Type 2 Diabetes Treated With Metformin
- ClinicalTrials.gov ID
- NCT00772174
- Acronym / sponsor ID
- PRISMA / IT-PIO-108
- 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
- Completed
- Enrolment
- 418 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Jan 2007
- Primary completion
- Feb 2008 (actual)
- Study completion
- Feb 2008 (actual)
- First posted
- 15 Oct 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 efficacy of pioglitazone taken with metformin on high-density lipoprotein cholesterol in subjects with Type 2 Diabetes.
Detailed description
Diabetes is none of the most common, chronic diseases worldwide and affects nearly 200 million people. It is the fourth or fifth leading cause of death in developed countries, and it is expected that diabetes will reach epidemic proportions, affecting 333 million people globally by 2025.
The metabolic syndrome is a cluster of the most dangerous cardiovascular risk factors and includes diabetes and pre-diabetes in addition to abdominal obesity, low high-density lipoprotein cholesterol, high triglycerides and hypertension. It is estimated that around a quarter of the world's adult population has metabolic syndrome, and are twice as likely to die and three times as likely to have a heart attack or stroke when compared to people without the syndrome. In addition, non-diabetic people with metabolic syndrome have a fivefold greater risk of developing type 2 diabetes. The clustering of cardiovascular risk factors that typifies the metabolic syndrome is now considered the driving force for a cardiovascular disease epidemic.
Metabolic syndrome has been recently defined by a Consensus Conference of the International Diabetes Federation as a cluster of clinical and laboratory signs characterized by the presence of abnormal deposition of fat tissue in the abdomen and visceral districts, and at least two other clinical and laboratory abnormalities, including altered glucose metabolism or type 2 diabetes and decreased levels of high-density lipoprotein cholesterol. One of the underlying pathophysiological mechanisms of metabolic syndrome is insulin resistance, characterized by an increased glucose output from the liver, and reduced glucose uptake in the muscle and adipose tissue cells. Drugs whose mechanism of action consists of increasing insulin sensitivity in the target tissues are able to reduce the clinical manifestations and consequences of metabolic syndrome.
While each individual component of metabolic syndrome confers an increased risk of cardiovascular-related complications or death, this risk is more pronounced when the syndrome itself is present. The more components of metabolic syndrome are evident, the higher is the cardiovascular mortality rate.
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 |
|---|---|---|
| Pioglitazone + Metformin | Experimental | Drug: Pioglitazone and Metformin |
| Metformin | Active comparator | Drug: Metformin |
Who may qualify
- Ages
- 35 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Diagnosis of Type 2 Diabetes Mellitus.
- Has glycosylated hemoglobin levels between 6.0% and 8.0%.
- Treatment with metformin (2,000 to 3,000 mg daily) for at least 3 months.
- Has reduced high-density lipoprotein cholesterol levels less than 40 mg/dl in males and less than 50 mg/dl in females, irrespective of treatment with statins.
- Has central obesity defined as a waist circumference greater than or equal to 94 cm for men and greater than or equal to 80 cm for females.
Key exclusion criteria (17 listed)
- Has a diagnosis of Type 1 Diabetes Mellitus.
- 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:
- Has any disease with malabsorption.
- Has acute or chronic pancreatitis.
- Has familial polyposis coli.
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 |
|---|---|---|
| Pioglitazone and MetforminAlso: ACTOS®, AD4833Pioglitazone 15 mg, tablets, orally, two-times daily and metformin stable dose, orally, three-times daily for 4 weeks; then increased to pioglitazone 15 mg, tablets, orally, three-times daily and metformin stable dose, orally, three-times daily for up to 20 weeks. | Drug | Pioglitazone + Metformin |
| MetforminPioglitazone placebo-matching tablets, orally, two-times daily and metformin stable dose, orally, three-times daily for 4 weeks; then increased to pioglitazone placebo-matching tablets, orally, three-times daily and metformin stable dose, orally, three-times daily for up to 20 weeks. | Drug | Metformin |
Primary outcome
Increase in High-Density Lipoprotein cholesterol levels.
Time frame: Final Visit.
5 secondary outcomes
The change from Baseline in Metabolic Syndrome, as defined by the International Diabetes Federation (aggregate waist circumference, fasting plasma glucose, triglycerides and high-density lipoprotein cholesterol).
Time frame: Weeks: 8 and 24.
The change from Baseline in Metabolic Syndrome, as defined by the International Diabetes Federation (blood pressure).
Time frame: At all Visits.
The change from Baseline in Individual Metabolic Parameters (insulin sensitivity and beta-cell function, inflammatory cytokines, adipokines, endothelial functionality).
Time frame: Weeks: 8 and 24.
Adverse Events.
Time frame: At all Visits.
The change from Baseline in Laboratory Parameters (hematology, chemistry and urinalysis).
Time frame: Weeks: 8 and 24.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2010.
- ACTOS® Package InsertLink provided by the sponsor.
Related trials for Diabetes Mellitus
Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Effects of Lean Pork Loin Intake on Protein Homeostasis and Glucose Regulation in Prediabetic Adults
Hyperglycaemia (Non Diabetic), Prediabetes
Recruiting
PAW-Hydrogel for Chronic Wound Healing
Diabetic Foot Ulcer (DFU), Pressure Ulcer (PU)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
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.
Medical Director study director
Takeda
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pioglitazone 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 6 inclusion and 17 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: finished, as of the sponsor's last update on 5 Jul 2010. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Increase in High-Density Lipoprotein cholesterol levels. (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 5 Jul 2010.