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| ID | Type | Description | Link |
|---|---|---|---|
| JapicCTI-132368 | Registry Identifier | JapicCTI | |
| JapicCTI-R150782 | Registry Identifier | JapicCTI |
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The purpose of this study is to investigate the safety and efficacy of long-term use of pioglitazone/metformin hydrochloride combination tablets in the routine clinical setting in patients with type 2 diabetes mellitus for whom therapy with pioglitazone hydrochloride combined with metformin hydrochloride is considered suitable.
This is a special drug use surveillance (survey on long-term use) designed to investigate the safety and efficacy of long-term use of pioglitazone/metformin hydrochloride combination tablets (Metact Combination Tablets) in patients with type 2 diabetes mellitus in the routine clinical setting.
The following items will also be studied:
The planned sample size was 1000 participants. The usual adult dosage is one tablet of Metact administered orally once daily after breakfast (15 mg/500 mg or 30 mg/500 mg of pioglitazone/metformin hydrochloride).
<Precautions Related to Dosage and Administration> Edema due to pioglitazone administration has been reported with comparative frequency in women. Therefore, it is preferable to be vigilant for edema and start Metact Combination Tablets at a dosage equivalent to 15 mg of pioglitazone once daily when administering the study drug to women.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pioglitazone/Metformin Hydrochloride | Pioglitazone/metformin hydrochloride combination tablets, orally, for 12 months as prescribed by the standard of care. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pioglitazone/metformin hydrochloride | Drug | Pioglitazone/metformin hydrochloride combination tablets |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Drug Reactions | Adverse events are defined as any unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product reported from the first dose of study drug to the last dose of study drug. Among these, events which are considered possibly associated with a medicinal product are defined as adverse drug reactions. | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Tabulation of the HbA1c test value and change at each test time point (test value at each test time point after baseline - test value at baseline). A negative change from Baseline indicates improvement. n=number of participants analyzed at each time point. Final assessment is defined as a cumulative assessment of Month 12 and Early Termination Visit data. |
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Inclusion Criteria:
-Patients with type 2 diabetes mellitus for whom a physician has concluded that therapy with pioglitazone hydrochloride combined with metformin hydrochloride is suitable and for whom long-term treatment with Metact Combination Tablets is considered necessary.
Exclusion Criteria:
-Patients for whom pioglitazone hydrochloride and metformin hydrochloride are contraindicated.
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Type 2 diabetes mellitus
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| Name | Affiliation | Role |
|---|---|---|
| Postmarketing Group Manager | Takeda | Study Chair |
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Patients with type 2 diabetes mellitus for whom a physician has concluded that therapy with pioglitazone hydrochloride combined with metformin hydrochloride is suitable and for whom long-term treatment with Metact Combination Tablets is considered necessary.
Participants took part in the study at 196 investigative sites in Japan from July 2010 to November 2013 (N=1103).
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| ID | Title | Description |
|---|---|---|
| FG000 | Pioglitazone/Metformin Hydrochloride | Pioglitazone/metformin hydrochloride combination tablets, orally, for 12 months as prescribed by the standard of care. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety analysis set
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| ID | Title | Description |
|---|---|---|
| BG000 | Pioglitazone/Metformin Hydrochloride | Pioglitazone/metformin hydrochloride combination tablets, orally, for 12 months as prescribed by the standard of care. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Adverse Drug Reactions | Adverse events are defined as any unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product reported from the first dose of study drug to the last dose of study drug. Among these, events which are considered possibly associated with a medicinal product are defined as adverse drug reactions. | Safety Analysis Set, all patients for whom data was collected in case report forms, except those who were treated before the contract period, those who were enrolled after Day 15 of the start of treatment with Metact Combination Tablets, and those with missing data after treatment (missed visits). | Posted | Number | participants | 12 months |
|
From baseline to 12 months of treatment.
At each visit the investigator documented occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by participant or observed by investigator was recorded, irrespective of relation to study treatment. The same PTs (Preferred Term) coded for same patient with differing LLTs (Low Level Terms) are counted twice.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pioglitazone/Metformin Hydrochloride | Pioglitazone/metformin hydrochloride combination tablets, orally, for 12 months as prescribed by the standard of care. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA version 16.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director, Clinical Science | Takeda Pharmaceuticals Company Limited | +1-877-825-3327 | trialdisclosures@takeda.com |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000077205 | Pioglitazone |
| D008687 | Metformin |
| ID | Term |
|---|---|
| D045162 | Thiazolidinediones |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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| Baseline and Months 3, 6, 9, 12 and final assessment |
| Change From Baseline in Fasting Blood Glucose | Tabulation of fasting blood glucose test values and change at each test time point (test value at each test time point after baseline - test value at baseline). A negative change from Baseline indicates improvement. n=number of participants analyzed at each time point. Final assessment is defined as a cumulative assessment of Month 12 and Early Termination Visit data. | Baseline and Months 3, 6, 9, 12 and final assessment |
| Change From Baseline in Fasting Insulin | Tabulation of fasting insulin test values and change at each test time point (test value at each test time point after baseline - test value at baseline). A negative change from Baseline indicates improvement. n=number of participants analyzed at each time point. Final assessment is defined as a cumulative assessment of Month 12 and Early Termination Visit data. | Baseline and Months 3, 6, 9, 12 and final assessment |
| years |
|
| Age, Customized | Number | participants |
|
| Age, Customized | Number | participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Pregnancy status (Females) | Female participants only (n=450) | Number | participants |
|
| Weight | Mean | Standard Deviation | kg |
|
| Weight, Customized | Number | participants |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
|
| Body Mass Index, Customized | Number | participants |
|
| Duration of Type 2 Diabetes | Mean | Standard Deviation | years |
|
| Duration of Type 2 Diabetes, Customized | Number | participants |
|
| Healthcare Category | Number | participants |
|
| History of Allergies | Number | participants |
|
| Presence of Complications | Number | participants |
|
| Breakdown of Complications | Participants may be counted in more than 1 category. DM=diabetes mellitus. | Number | participants |
|
| Complications: Breakdown of Diabetic Complications | Only participants with diabetic complications are reported. Participants may also be counted in more than 1 category. | Number | participants |
|
| Complications: Breakdown of Lifestyle-Related Diseases (Excluding Diabetes Mellitus) | Participants may be counted in more than 1 category. | Number | participants |
|
| Complications: Breakdown of Liver Diseases | Only participants with liver diseases are reported. Participants may also be counted in more than 1 category. | Number | participants |
|
| Complications: Breakdown of Renal Diseases | Only participants with renal diseases are reported. Participants may also be counted in more than 1 category. | Number | participants |
|
| Complications: Breakdown of Heart or Cerebrovascular Diseases | Only participants with heart or cerebrovascular diseases are reported. Participants may also be counted in more than 1 category. | Number | participants |
|
| Stages of Cardiac Failure (New York Heart Association [NYHA] Classification) | Only participants with cardiac failure are reported. NYHA Class definitions are as follows: Class I - No limitation of physical activity; Class II - Slight limitation of physical activity; Class III - Marked limitation of physical activity; Class IV - Unable to carry on any physical activity without discomfort. | Number | participants |
|
| Complications: Breakdown of Allergic Conditions | Only participants with allergic conditions are reported. Participants may also be counted in more than 1 category. | Number | participants |
|
| Complications: Breakdown of Malignant Tumors | Only participants with malignant tumors are reported. Participants may also be counted in more than 1 category. | Number | participants |
|
| Presence of Medical History | Breakdown of medical history was categorized as liver disease, renal disease, heart disease, cerebrovascular disease, malignant tumor and any other disease from those mentioned above. Only participants with medical history are presented. | Number | participants |
|
| Alcohol History (Drinking Alcohol-Containing Beverages Nearly Every Day) | Number | participants |
|
| Smoking Classification | Number | participants |
|
| Status of Administration of Pioglitazone and Metformin Prior to Dosing of Metact Combination Tablets | Number | participants |
|
| Daily Dose of Pioglitazone Prior to Dosing of Metact Combination Tablets | Mean | Standard Deviation | mg/day |
|
| Daily Dose of Pioglitazone Prior to Dosing of Metact Combination Tablets | 348 participants did not take pioglitazone prior to dosing of Metact combination tablet. | Number | participants |
|
| Daily Dose of Pioglitazone Before Switching to Metact Combination Tablets,and Metact Dose Assignment | Metact LD=1 tablet of Metact Combination Tablets low dose. Metact HD=1 tablet Metact Combination Tablets high dose, Pio=Pioglitazone. 348 participants did not take pioglitazone prior to dosing of Metact combination tablet. | Number | participants |
|
| Daily Dose of Metformin Prior to Dosing of Metact Combination Tablets | Mean | Standard Deviation | mg/day |
|
| Daily Dose of Metformin Prior to Dosing of Metact Combination Tablets | Participants may be counted in more than 1 category. | Number | participants |
|
| Daily Dose of Metformin Before Switching to Metact Combination Tablets,and Metact Dose Assignment | Metact LD=1 tablet of Metact Combination Tablets low dose. Metact HD=1 tablet Metact Combination Tablets high dose, Pio=Pioglitazone. Participants could be counted in more than 1 category. 579 participants did not take Metformin prior to dosing of Metact combination tablet. | Number | participants |
|
| Compliance Status of Pioglitazone (Within 3 Months Before Switching to Metact Combination Tablets) | 348 participants did not take pioglitazone prior to dosing of Metact combination tablet. | Number | participants |
|
| Compliance Status of Metformin (Within 3 Months Before Switching to Metact Combination Tablets) | 579 participants did not take Metformin prior to dosing of Metact combination tablet. | Number | participants |
|
| Frequency of daily dosing of Metformin prior to dosing of Metact Combination Tablets | 579 participants did not take Metformin prior to dosing of Metact combination tablet. TID = Three times a day. | Number | participants |
|
| Switch from metformin (> 500 mg/day) to Metact Combination Tablets | Number | participants |
|
| Response to pioglitazone in Pioglitazone monotherapy prior to dosing of Metact Combination Tablets | 625 participants did not take pioglitazone in pioglitazone monotherapy prior to dosing of Metact combination tablet. | Number | participants |
|
| Daily dose in Pioglitazone monotherapy prior to dosing of Metact Combination Tablets | Participants who responded poorly to pioglitazone treatment were reported. 760 participants did not take pioglitazone in Pioglitazone monotherapy prior to dosing of Metact combination tablet in patients who responded poorly to pioglitazone treatment. | Mean | Standard Deviation | mg/day |
|
| Daily dose in Pioglitazone monotherapy prior to dosing of Metact Combination Tablets | Participants who responded poorly to pioglitazone treatment were reported. 760 participants did not take pioglitazone in Pioglitazone monotherapy prior to dosing of Metact combination tablet in patients who responded poorly to pioglitazone treatment. | Number | participants |
|
| Daily dose in Pioglitazone monotherapy prior to switching to Metact Combination Tablets | Participants who responded poorly to pioglitazone treatment were reported. 760 participants did not take pioglitazone in Pioglitazone monotherapy prior to dosing of Metact combination tablet in patients who responded poorly to pioglitazone treatment. | Number | participants |
|
| Rate of compliance with the diet regimen at the start of treatment with Metact Combination Tablets | Number | participants |
|
| Rate of compliance with exercise regimen at the start of treatment with Metact Combination Tablets | Number | participants |
|
| HbA1c (NGSP value) at the start of treatment with Metact Combination Tablets | HbA1c = glycosylated hemoglobin NGSP = National Glycohemoglobin Standardization Program | Mean | Standard Deviation | percentage of HbA1c |
|
| Participants with HbA1c (NGSP value) at the start of treatment with Metact Combination Tablets | Number | participants |
|
| Fasting blood glucose at the start of treatment with Metact Combination Tablets | Mean | Standard Deviation | mg/dL |
|
| Participants with Fasting blood glucose at the start of treatment with Metact Combination Tablets | Number | participants |
|
| Fasting insulin at the start of treatment with Metact Combination Tablets | Mean | Standard Deviation | μU/dL |
|
| Participants with Fasting insulin at the start of treatment with Metact Combination Tablets | Number | participants |
|
|
|
| Secondary | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Tabulation of the HbA1c test value and change at each test time point (test value at each test time point after baseline - test value at baseline). A negative change from Baseline indicates improvement. n=number of participants analyzed at each time point. Final assessment is defined as a cumulative assessment of Month 12 and Early Termination Visit data. | The analysis was performed in the efficacy assessment population (n=905). | Posted | Mean | Standard Deviation | percentage of HbA1c | Baseline and Months 3, 6, 9, 12 and final assessment |
|
|
|
| Secondary | Change From Baseline in Fasting Blood Glucose | Tabulation of fasting blood glucose test values and change at each test time point (test value at each test time point after baseline - test value at baseline). A negative change from Baseline indicates improvement. n=number of participants analyzed at each time point. Final assessment is defined as a cumulative assessment of Month 12 and Early Termination Visit data. | The analysis was performed in the efficacy assessment population (n=905). | Posted | Mean | Standard Deviation | mg/dL | Baseline and Months 3, 6, 9, 12 and final assessment |
|
|
|
| Secondary | Change From Baseline in Fasting Insulin | Tabulation of fasting insulin test values and change at each test time point (test value at each test time point after baseline - test value at baseline). A negative change from Baseline indicates improvement. n=number of participants analyzed at each time point. Final assessment is defined as a cumulative assessment of Month 12 and Early Termination Visit data. | The analysis was performed in the efficacy assessment population (n=905). | Posted | Mean | Standard Deviation | μU/dL | Baseline and Months 3, 6, 9, 12 and final assessment |
|
|
|
| 18 |
| 1,067 |
| 0 |
| 1,067 |
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 16.0 | Systematic Assessment |
|
| Gastric cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 16.0 | Systematic Assessment |
|
| Malignant ascites | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 16.0 | Systematic Assessment |
|
| Rectal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 16.0 | Systematic Assessment |
|
| Uterine cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 16.0 | Systematic Assessment |
|
| Thyroid cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 16.0 | Systematic Assessment |
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| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA version 16.0 | Systematic Assessment |
|
| Cerebral infarction | Nervous system disorders | MedDRA version 16.0 | Systematic Assessment |
|
| Diabetic hyperglycaemic coma | Nervous system disorders | MedDRA version 16.0 | Systematic Assessment |
|
| Acute myocardial infarction | Cardiac disorders | MedDRA version 16.0 | Systematic Assessment |
|
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA version 16.0 | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA version 16.0 | Systematic Assessment |
|
| Liver disorder | Hepatobiliary disorders | MedDRA version 16.0 | Systematic Assessment |
|
| Nephrolithiasis | Renal and urinary disorders | MedDRA version 16.0 | Systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | MedDRA version 16.0 | Systematic Assessment |
|
| Renal impairment | Renal and urinary disorders | MedDRA version 16.0 | Systematic Assessment |
|
| Sudden death | General disorders | MedDRA version 16.0 | Systematic Assessment |
|
| Femur fracture | Injury, poisoning and procedural complications | MedDRA version 16.0 | Systematic Assessment |
|
| Radius fracture | Injury, poisoning and procedural complications | MedDRA version 16.0 | Systematic Assessment |
|
| Ulna fracture | Injury, poisoning and procedural complications | MedDRA version 16.0 | Systematic Assessment |
|
| Heat illness | Injury, poisoning and procedural complications | MedDRA version 16.0 | Systematic Assessment |
|
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
| D004700 | Endocrine System Diseases |
| D001393 |
| Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| Title | Measurements |
|---|---|
|
| Month 12 (n=670) |
|
| Final Assessment (n=896) |
|
| Title | Measurements |
|---|---|
|
| Month 12 (n=255) |
|
| Final Assessment (n=375) |
|
| Title | Measurements |
|---|---|
|
| Month 12 (n=51) |
|
| Final Assessment (n=63) |
|