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| ID | Type | Description | Link |
|---|---|---|---|
| JapicCTI-080629 | Registry Identifier | JapicCTI | |
| UMIN000001394 | Registry Identifier | UMIN-CTR | |
| U1111-1119-6303 | Registry Identifier | WHO |
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The purpose of this study was evaluate the efficacy and safety of alogliptin, once dairy (QD) combined with metformin taken twice daily (BID) or three times daily (TID) in type 2 diabetic patients with uncontrolled blood glucose.
Both insulin hyposecretion and insulin-resistance are considered to be involved in the development of type 2 diabetes mellitus.
Takeda is developing SYR-322 (alogliptin) for the improvement of glycemic control in patients with type 2 diabetes mellitus. Alogliptin is an inhibitor of the dipeptidyl peptidase IV (DPP-IV) enzyme. DPP-IV is thought to be primarily responsible for the degradation of 2 peptide hormones released in response to nutrient ingestion. It is expected that inhibition of DPP-IV will improve glycemic control in patients with type 2 diabetes.
The present study was planned to evaluate the efficacy and safety of alogliptin as an add-on to metformin in type 2 diabetic patients who have uncontrolled blood glucose despite treatment with metformin as well as diet and exercise therapies.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Alogliptin 12.5 mg QD and metformin 500mg BID or 750mg TID | Active Comparator |
| |
| Alogliptin 25mg QD and metformin 500mg BID or 750mg TID | Active Comparator |
| |
| Metformin 500mg BID or 750mg TID | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alogliptin and metformin | Drug | Alogliptin 12.5 mg, tablets, orally, once daily and metformin 250 mg, tablets, orally, twice or three times daily for up 12 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (Week 12). | The change in 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 week 12 or final visit and glycosylated hemoglobin collected at baseline. | Baseline and Week 12. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (Week 2). | The change in 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 week 2 and glycosylated hemoglobin collected at baseline. | Baseline and Week 2. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Professor, Diabetes and Endocrine Division | Department of Medicine, Kawasaki Medical School | Study Director |
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Participants with a historical diagnosis of type 2 diabetes mellitus with uncontrolled blood glucose despite treatment with metformin as well as diet and exercise were enrolled in one of 3, once-daily (QD), twice daily (BID) or three times daily (TID) treatment groups.
Participants enrolled at 30 investigative sites in Japan from 22 August 2008 to 28 April 2009.
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| ID | Title | Description |
|---|---|---|
| FG000 | Alogliptin 12.5 mg QD and Metformin 500mg BID or 750mg TID | Alogliptin 12.5 mg, tablets, orally, once daily and metformin 250 mg, tablets, orally, twice or three times daily for up 12 weeks. |
| FG001 | Alogliptin 25mg QD and Metformin 500mg BID or 750mg TID | Alogliptin 25 mg, tablets, orally, once daily and metformin 250 mg, tablets, orally, twice or three times daily for up 12 weeks. |
| FG002 | Metformin 500mg BID or 750mg TID | Metformin 250 mg, tablets, orally, twice or three times daily and alogliptin placebo-matching tablets, orally, once daily for up 12 weeks. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Alogliptin 12.5 mg QD and Metformin 500mg BID or 750mg TID | Alogliptin 12.5 mg, tablets, orally, once daily and metformin 250 mg, tablets, orally, twice or three times daily for up 12 weeks. |
| BG001 | Alogliptin 25mg QD and Metformin 500mg BID or 750mg TID |
| 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 | Change From Baseline in Glycosylated Hemoglobin (Week 12). | The change in 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 week 12 or final visit and glycosylated hemoglobin collected at baseline. | Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set. | Posted | Mean | Standard Deviation | percentage of Glycosylated Hemoglobin | Baseline and Week 12. |
|
Treatment-emergent adverse events are any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 30 days after receiving the last dose of study drug.
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
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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 | Alogliptin 12.5 mg QD and Metformin 500mg BID or 750mg TID | Alogliptin 12.5 mg, tablets, orally, once daily and metformin 250 mg, tablets, orally, twice or three times daily for up 12 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (12.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| General Manager | Japan Development Center, Pharmaceutical Development Division | +81-6-6204-5257 | clinicaltrialregistry@tpna.com |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C520853 | alogliptin |
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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|
| Alogliptin and metformin | Drug | Alogliptin 25 mg, tablets, orally, once daily and metformin 250 mg, tablets, orally, twice or three times daily for up 12 weeks. |
|
|
| Metformin | Drug | Metformin 250 mg, tablets, orally, twice or three times daily and alogliptin placebo-matching tablets, orally, once daily for up 12 weeks. |
|
|
| Change From Baseline in Glycosylated Hemoglobin (Week 4). |
The change in 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 week 4 and glycosylated hemoglobin collected at baseline. |
| Baseline and Week 4. |
| Change From Baseline in Glycosylated Hemoglobin (Week 8). | The change in 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 week 8 and glycosylated hemoglobin collected at baseline. | Baseline and Week 8. |
| Change From Baseline in Fasting Plasma Glucose (Week 2). | The change between the value of fasting plasma glucose collected at week 2 and baseline. | Baseline and Week 2. |
| Change From Baseline in Fasting Plasma Glucose (Week 4). | The change between the value of fasting plasma glucose collected at week 4 and baseline. | Baseline and Week 4. |
| Change From Baseline in Fasting Plasma Glucose (Week 8). | The change between the value of fasting plasma glucose collected at week 8 and baseline. | Baseline and Week 8. |
| Change From Baseline in Fasting Plasma Glucose (Week 12). | The change between the value of fasting plasma glucose collected at week 12 or final visit and baseline. | Baseline and Week 12. |
| Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Week 12). | The change between the value of blood glucose measured by the meal tolerance test collected at week 12 or final visit and blood glucose measured by the meal tolerance test collected at baseline. Meal tolerance test measures blood glucose through blood samples drawn before a meal and at 2 hours after the start of the meal. | Baseline and Week 12. |
| Schedule Conflict |
|
Alogliptin 25 mg, tablets, orally, once daily and metformin 250 mg, tablets, orally, twice or three times daily for up 12 weeks. |
| BG002 | Metformin 500mg BID or 750mg TID | Metformin 250 mg, tablets, orally, twice or three times daily and alogliptin placebo-matching tablets, orally, once daily for up 12 weeks. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Alogliptin 25mg QD and Metformin 500mg BID or 750mg TID | Alogliptin 25 mg, tablets, orally, once daily and metformin 250 mg, tablets, orally, twice or three times daily for up 12 weeks. |
| OG002 | Metformin 500mg BID or 750mg TID | Metformin 250 mg, tablets, orally, twice or three times daily and alogliptin placebo-matching tablets, orally, once daily for up 12 weeks. |
|
|
|
| Secondary | Change From Baseline in Glycosylated Hemoglobin (Week 2). | The change in 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 week 2 and glycosylated hemoglobin collected at baseline. | Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set. | Posted | Mean | Standard Deviation | percentage of Glycosylated Hemoglobin | Baseline and Week 2. |
|
|
|
|
| Secondary | Change From Baseline in Glycosylated Hemoglobin (Week 4). | The change in 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 week 4 and glycosylated hemoglobin collected at baseline. | Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set. | Posted | Mean | Standard Deviation | percentage of Glycosylated Hemoglobin | Baseline and Week 4. |
|
|
|
|
| Secondary | Change From Baseline in Glycosylated Hemoglobin (Week 8). | The change in 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 week 8 and glycosylated hemoglobin collected at baseline. | Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set. | Posted | Mean | Standard Deviation | percentage of Glycosylated Hemoglobin | Baseline and Week 8. |
|
|
|
|
| Secondary | Change From Baseline in Fasting Plasma Glucose (Week 2). | The change between the value of fasting plasma glucose collected at week 2 and baseline. | Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set. | Posted | Mean | Standard Deviation | mg/dL | Baseline and Week 2. |
|
|
|
|
| Secondary | Change From Baseline in Fasting Plasma Glucose (Week 4). | The change between the value of fasting plasma glucose collected at week 4 and baseline. | Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set. | Posted | Mean | Standard Deviation | mg/dL | Baseline and Week 4. |
|
|
|
|
| Secondary | Change From Baseline in Fasting Plasma Glucose (Week 8). | The change between the value of fasting plasma glucose collected at week 8 and baseline. | Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set. | Posted | Mean | Standard Deviation | mg/dL | Baseline and Week 8. |
|
|
|
|
| Secondary | Change From Baseline in Fasting Plasma Glucose (Week 12). | The change between the value of fasting plasma glucose collected at week 12 or final visit and baseline. | Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set. | Posted | Mean | Standard Deviation | mg/dL | Baseline and Week 12. |
|
|
|
|
| Secondary | Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Week 12). | The change between the value of blood glucose measured by the meal tolerance test collected at week 12 or final visit and blood glucose measured by the meal tolerance test collected at baseline. Meal tolerance test measures blood glucose through blood samples drawn before a meal and at 2 hours after the start of the meal. | Analysis based on last observation carried forward, where the last postbaseline double-blind observed value is carried forward and used for all subsequent scheduled time points where data is missing. Values are from the Full Analysis Set. | Posted | Mean | Standard Deviation | mg/dL | Baseline and Week 12. |
|
|
|
|
| 0 |
| 92 |
| 32 |
| 92 |
| EG001 | Alogliptin 25mg QD and Metformin 500mg BID or 750mg TID | Alogliptin 25 mg, tablets, orally, once daily and metformin 250 mg, tablets, orally, twice or three times daily for up 12 weeks. | 2 | 96 | 37 | 96 |
| EG002 | Metformin 500mg BID or 750mg TID | Metformin 250 mg, tablets, orally, twice or three times daily and alogliptin placebo-matching tablets, orally, once daily for up 12 weeks. | 0 | 100 | 29 | 100 |
| Mallory-Weiss syndrome | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Conjunctivitis allergic | Eye disorders | MedDRA (12.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hepatic steatosis | Hepatobiliary disorders | MedDRA (12.0) | Systematic Assessment |
|
| Blood lactic acid increased | Investigations | MedDRA (12.0) | Systematic Assessment |
|
The clinical trial contract states that information should never be disclosed without prior consent of the sponsor, although it does not specify the number of days during which disclosure of information is limited.
| Mean Difference (Final Values) |
| -0.192 |
| 2-Sided |
| 95 |
| -0.242 |
| -0.143 |
| No |
| Superiority or Other |
| Mean Difference (Final Values) |
| -0.403 |
| 2-Sided |
| 95 |
| -0.484 |
| -0.323 |
| No |
| Superiority or Other |
| Hazard Ratio, log |
| -0.692 |
| 2-Sided |
| 95 |
| -0.814 |
| -0.569 |
| No |
| Superiority or Other |
| Mean Difference (Final Values) |
| -23.27 |
| 2-Sided |
| 95 |
| -30.43 |
| -16.12 |
| No |
| Superiority or Other |
| Mean Difference (Final Values) |
| -21.35 |
| 2-Sided |
| 95 |
| -28.32 |
| -14.39 |
| No |
| Superiority or Other |
| Mean Difference (Final Values) |
| -18.16 |
| 2-Sided |
| 95 |
| -25.43 |
| -10.90 |
| No |
| Superiority or Other |
| Mean Difference (Final Values) |
| -22.38 |
| 2-Sided |
| 95 |
| -30.87 |
| -13.88 |
| No |
| Superiority or Other |
| Mean Difference (Final Values) |
| -6.41 |
| 2-Sided |
| 95 |
| -16.34 |
| 3.52 |
| No |
| Superiority or Other |