Diabetes MellitusPhase 3NCT00770952
Efficacy of Pioglitazone and Glimepiride Combination Therapy in Treating Subjects With Type 2 Diabetes Mellitus.
A Phase 3 study testing Pioglitazone and Glimepiride and Glimepiride in people with Diabetes Mellitus, run by Takeda at 17 sites in Germany.
Trial summary
The purpose of this study is to determine the effect of pioglitazone, once daily (QD), and glimepiride combination therapy compared to glimepiride monotherapy in subjects with Type 2 Diabetes. Read more about this study
- Who is it for?
- Ages 30 to 75 years
- Conditions the study is for
- Diabetes Mellitus
- What is being tested?
- Pioglitazone and Glimepiride and Glimepiride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 91 participants
- Where
- 17 sitesGermany
- Study dates
- Dec 2006to Dec 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 30 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 2 Diabetes according to the American Diabetes Association Criteria.
- Treatment with Glimepiride monotherapy (1-3 mg per day) 3 months before entering the study.
- Glycosylated hemoglobin greater than 6.5%, but less than 8.5% and/ or fasting plasma glucose greater than 7 mmol/l within the last 4 weeks.
- 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
- Type 1 Diabetes mellitus.
- History of hypersensitivity to the study drugs or to drugs with similar chemical structures.
- Progressive fatal disease.
- History of drug or alcohol abuse during the last 5 years.
- More than one unexplained episode of severe hypoglycemia within 6 months prior to entering the study.
- A history of significant cardiovascular (New York Heart Association stage I - IV), respiratory, gastrointestinal, hepatic (alanine aminotransferase greater than 2.5 times the upper limit of the normal reference range), renal (serum creatinine greater than 1.8 mg/dl; glomerular filtration rate less than 40 ml/min as estimated by the Cockroft-Gault formula), neurological, psychiatric and/or hematological disease, history of macular edema.
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- Blood donation within the last 30 days.
- Is 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:
- CYP2C9 inductors
- CYP2C9 inhibitors
- rifampicin
- fluconazole
- drugs used for treating type 2 diabetes (insulin, insulin analogous compounds and oral antidiabetic drugs)
- Pretreatment with thiazolidinediones within the last 12 months.
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
Germany17 sites
Study site
Aschaffenburg, Bavaria
Study site
Berlin, State of Berlin
Study site
Dortmund, North Rhine-Westphalia
Study site
Frankfurt am Main, Hesse
Study site
Friedrichsthal, Saarland
Study site
Frielendorf, Hesse
Study site
Hanover, Lower Saxony
Study site
Ingolstadt, Bavaria
Study site
Kallstadt, Rhineland-Palatinate
Study site
Mainz, Rhineland-Palatinate
Study site
Mayen, Rhineland-Palatinate
Study site
Meissen, Saxony
Study site
Neuwied, Rhineland-Palatinate
Study site
Rhaunen, Rhineland-Palatinate
Study site
Rotenburg an der Fulda, Hesse
Study site
Siegen, North Rhine-Westphalia
Study site
Villingen-Schwenningen, Baden-Wurttemberg
About this study
Official title: Effects of Pioglitazone in Combination With Glimepiride in Comparison to Glimepiride Monotherapy on Metabolic Control in Patients With Type 2 Diabetes Mellitus
The purpose of this study is to determine the effect of pioglitazone, once daily (QD), and glimepiride combination therapy compared to glimepiride monotherapy in subjects with Type 2 Diabetes.
Read the detailed description
Tight glycemic control is mandatory for the prevention and treatment of vascular complications in patients suffering from diabetes mellitus. After onset of Type 2 Diabetes, patients are usually treated with diet along with or without different combinations of oral drugs. One first-line drug class are sulfonylurea drugs that are preferably provided to patients who are not obese. The mode of action of sulfonylurea drugs is to increase beta-cell secretion, but it could be shown that they lead to deterioration of the beta-cell secretion product over time, resulting in increased proinsulin secretion. Since proinsulin is an independent cardiovascular risk factor, recent publications have demonstrated an increased risk for cardiovascular events in patients treated with sulfonylurea drugs as compared to other treatment methods.
Combination therapy of sulfonylurea drugs with glitazones has been shown to counterbalance the effect of deteriorated beta-cell secretion and to improve insulin sensitivity and the levels of proinsulin, C-peptide and other laboratory surrogate markers for cardiovascular risk. Proving that the treatment of diabetic patients with higher doses of beta cytotropic agents can be avoided and beta-cell function can be preserved by using pioglitazone in combination with low dose sulfonylurea drugs, it will be possible to optimize the treatment of patients with type 2 diabetes who are not controlled efficiently by sulfonylurea drugs monotherapy.
In this study patients will be enrolled who are inefficiently treated with a Glimepiride monotherapy. Patients will be either randomized to a combinational therapy of Pioglitazone and Glimepiride or Glimepiride monotherapy. If possible, study medication will be up-titrated to maximal dosage levels in both treatment arms to observe maximal and comparable treatment effects. Stable effects on beta-cell function will be observed after 24 weeks of treatment.
- Conditions
- Diabetes Mellitus
- Being tested
- Pioglitazone and Glimepiride, Glimepiride
- 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 GlimepirideDrug
Also called ACTOS®
Pioglitazone 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.
GlimepirideDrug
Pioglitazone 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.
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone 30 mg to 45 mg QD + Glimepiride 2 mg to 4 mg QD | Experimental | Not described Receives: Drug: Pioglitazone and Glimepiride |
| Glimepiride 4 mg to 6 mg QD | Active comparator | Not described Receives: Drug: Glimepiride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline in Homeostatic Model Assessment - Beta cell.
Measured: Week: 24 or Final Visit beyond week 12.
Secondary outcomes (12)
Change from Baseline in Glycosylated Hemoglobin.
Measured: Week: 24 or Final Visit beyond week 12.
Change from Baseline in oral glucose tolerance testing.
Measured: Week: 24 or Final Visit beyond week 12.
Change from Baseline in Insulin.
Measured: Week: 24 or Final Visit beyond week 12.
Change from Baseline in Proinsulin.
Measured: Week: 24 or Final Visit beyond week 12.
Change from Baseline in C-peptide.
Measured: Week: 24 or Final Visit beyond week 12.
Change from Baseline in High sensitivity C-Reactive Protein.
Measured: Week: 24 or Final Visit beyond week 12.
Change from Baseline in Adiponectin.
Measured: Week: 24 or Final Visit beyond week 12.
Change from Baseline in Homeostatic Model Assessment - Sensitivity.
Measured: Week: 24 or Final Visit beyond week 12.
Change from Baseline in Triglycerides
Measured: Week: 24 or Final Visit beyond week 12.
Change from Baseline in Low Density Lipoprotein-Cholesterol
Measured: Week: 24 or Final Visit beyond week 12.
Change from Baseline in High Density Lipoprotein-Cholesterol
Measured: Week: 24 or Final Visit beyond week 12.
Change from Baseline in Total Cholesterol
Measured: Week: 24 or Final Visit beyond week 12.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2008 (estimated)
- Study startDec 2006
- Primary completionDec 2008
- Study completionDec 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
- 91 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Medical Adviser Clinical Research, Study director, Takeda Pharma Gmbh, Aachen (Germany)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00770952
- Sponsor's protocol ID
- ATS K020
- Other IDs
- 2006-002271-41, D-PIO-112, U1111-1114-3221
- Status last verified
- Jul 2010
- First submitted
- 9 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
- Effects of Pioglitazone in Combination With Glimepiride in Comparison to Glimepiride Monotherapy on Metabolic Control in Patients With Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT00770952
- Acronym / sponsor ID
- ATS K020
- 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
- 91 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Dec 2006
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 10 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 is to determine the effect of pioglitazone, once daily (QD), and glimepiride combination therapy compared to glimepiride monotherapy in subjects with Type 2 Diabetes.
Detailed description
Tight glycemic control is mandatory for the prevention and treatment of vascular complications in patients suffering from diabetes mellitus. After onset of Type 2 Diabetes, patients are usually treated with diet along with or without different combinations of oral drugs. One first-line drug class are sulfonylurea drugs that are preferably provided to patients who are not obese. The mode of action of sulfonylurea drugs is to increase beta-cell secretion, but it could be shown that they lead to deterioration of the beta-cell secretion product over time, resulting in increased proinsulin secretion. Since proinsulin is an independent cardiovascular risk factor, recent publications have demonstrated an increased risk for cardiovascular events in patients treated with sulfonylurea drugs as compared to other treatment methods.
Combination therapy of sulfonylurea drugs with glitazones has been shown to counterbalance the effect of deteriorated beta-cell secretion and to improve insulin sensitivity and the levels of proinsulin, C-peptide and other laboratory surrogate markers for cardiovascular risk. Proving that the treatment of diabetic patients with higher doses of beta cytotropic agents can be avoided and beta-cell function can be preserved by using pioglitazone in combination with low dose sulfonylurea drugs, it will be possible to optimize the treatment of patients with type 2 diabetes who are not controlled efficiently by sulfonylurea drugs monotherapy.
In this study patients will be enrolled who are inefficiently treated with a Glimepiride monotherapy. Patients will be either randomized to a combinational therapy of Pioglitazone and Glimepiride or Glimepiride monotherapy. If possible, study medication will be up-titrated to maximal dosage levels in both treatment arms to observe maximal and comparable treatment effects. Stable effects on beta-cell function will be observed after 24 weeks of treatment.
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 30 mg to 45 mg QD + Glimepiride 2 mg to 4 mg QD | Experimental | Drug: Pioglitazone and Glimepiride |
| Glimepiride 4 mg to 6 mg QD | Active comparator | Drug: Glimepiride |
Who may qualify
- Ages
- 30 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Type 2 Diabetes according to the American Diabetes Association Criteria.
- Treatment with Glimepiride monotherapy (1-3 mg per day) 3 months before entering the study.
- Glycosylated hemoglobin greater than 6.5%, but less than 8.5% and/ or fasting plasma glucose greater than 7 mmol/l within the last 4 weeks.
- 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.
Key exclusion criteria (14 listed)
- Type 1 Diabetes mellitus.
- History of hypersensitivity to the study drugs or to drugs with similar chemical structures.
- Progressive fatal disease.
- History of drug or alcohol abuse during the last 5 years.
- More than one unexplained episode of severe hypoglycemia within 6 months prior to entering 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 |
|---|---|---|
| Pioglitazone and GlimepirideAlso: ACTOS®Pioglitazone 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. | Drug | Pioglitazone 30 mg to 45 mg QD + Glimepiride 2 mg to 4 mg QD |
| GlimepiridePioglitazone 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. | Drug | Glimepiride 4 mg to 6 mg QD |
Primary outcome
Change from Baseline in Homeostatic Model Assessment - Beta cell.
Time frame: Week: 24 or Final Visit beyond week 12.
12 secondary outcomes
Change from Baseline in Glycosylated Hemoglobin.
Time frame: Week: 24 or Final Visit beyond week 12.
Change from Baseline in oral glucose tolerance testing.
Time frame: Week: 24 or Final Visit beyond week 12.
Change from Baseline in Insulin.
Time frame: Week: 24 or Final Visit beyond week 12.
Change from Baseline in Proinsulin.
Time frame: Week: 24 or Final Visit beyond week 12.
Change from Baseline in C-peptide.
Time frame: Week: 24 or Final Visit beyond week 12.
Change from Baseline in High sensitivity C-Reactive Protein.
Time frame: Week: 24 or Final Visit beyond week 12.
Change from Baseline in Adiponectin.
Time frame: Week: 24 or Final Visit beyond week 12.
Change from Baseline in Homeostatic Model Assessment - Sensitivity.
Time frame: Week: 24 or Final Visit beyond week 12.
Change from Baseline in Triglycerides
Time frame: Week: 24 or Final Visit beyond week 12.
Change from Baseline in Low Density Lipoprotein-Cholesterol
Time frame: Week: 24 or Final Visit beyond week 12.
Change from Baseline in High Density Lipoprotein-Cholesterol
Time frame: Week: 24 or Final Visit beyond week 12.
Change from Baseline in Total Cholesterol
Time frame: Week: 24 or Final Visit beyond week 12.
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.
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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.
Medical Adviser Clinical Research study director
Takeda Pharma Gmbh, Aachen (Germany)
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pioglitazone and Glimepiride and Glimepiride in people with Diabetes Mellitus, run by Takeda at 17 sites in Germany.
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 4 inclusion and 14 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.
Where is the study taking place?
The record lists 17 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Change from Baseline in Homeostatic Model Assessment - Beta cell. (time frame: Week: 24 or Final Visit beyond week 12.). 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.