A Long-term, Open-label Extension Study to Investigate the Long-term Safety of Alogliptin When Used in Combination With Sulfonylurea or Metformin in Subjects With Type 2 Diabetes in Japan
| Registry | NCT01318135 |
|---|
| Status | Completed |
|---|
| Phase | Phase 2 / Phase 3 |
|---|
| Study type | Interventional; randomized, parallel, masking: none, treatment |
|---|
| Enrollment | 576 (Actual) |
|---|
| Sponsor | Takeda (Industry) |
|---|
| Conditions | Type 2 Diabetes Mellitus |
|---|
| Interventions | Alogliptin and glimepiride, Alogliptin and metformin (Drug) |
|---|
| Dates | start 2009-01-01, primary completion 2010-01-01, completion 2010-04-01, first posted 2011-03-18, last updated 2012-08-16 |
|---|
Related Papers Related Patents Related Grants Related Experts
All trials for Type 2 Diabetes Mellitus All trials of Alogliptin and glimepiride All trials of Alogliptin and metformin
-Summary
To evaluate the efficacy and safety of alogliptin administered as an add-on to sulfonylurea (glimepiride) or metformin, once daily (QD), twice daily (BID) or three times daily (TID).
Expand all sections · Collapse all
+Detailed description
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.
This was a phase 2/3, multicenter, open-label study, in participants who had completed the core phase 2/3 sulfonylurea add-on study (SYR-322/CCT-005; NCT01318083) or the core phase 2/3 metformin add-on study (SYR-322/CCT-006; NCT01318109) to evaluate the safety and efficacy of alogliptin administered as an add-on to a sulfonylurea (glimepiride) or metformin continuously for 40 weeks (52 weeks from the start of study treatment with alogliptin in the core phase 2/3 sulfonylurea add-on study or the core phase 2/3 metformin add-on study).
+Arms and interventions
| Arm | Type | Interventions | Description |
|---|
| Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID | Active comparator | Drug: Alogliptin and glimepiride | |
| Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID | Active comparator | Drug: Alogliptin and glimepiride | |
| Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID | Active comparator | Drug: Alogliptin and metformin | |
| Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID | Active comparator | Drug: Alogliptin and metformin | |
- Alogliptin and glimepiride (Drug), also known as SYR-322, Amaryl: Alogliptin 12.5 mg, tablets, orally, once daily and sulfonylurea 1, 2, 3, 4, 5 or 6 mg, tablets, orally, once or twice daily for up to 52 weeks.
- Alogliptin and glimepiride (Drug), also known as SYR-322, Amaryl: Alogliptin 25 mg, tablets, orally, once daily and sulfonylurea 1, 2, 3, 4, 5 or 6 mg, tablets, orally, once or twice daily for up to 52 weeks.
- Alogliptin and metformin (Drug), also known as SYR-322, Glycoran: Alogliptin 12.5 mg, tablets, orally, once daily and metformin 500 mg, tablets, orally, twice daily or metformin 750 mg, tablets, orally, three times daily for up to 52 weeks.
- Alogliptin and metformin (Drug), also known as SYR-322, Glycoran: Alogliptin 25 mg, tablets, orally, once daily and metformin 500 mg, tablets, orally, twice daily or metformin 750 mg, tablets, orally, three times daily for up to 52 weeks.
+Outcome measures
Primary outcomes
- Number of Participants With Adverse Events. [52 Weeks.]: Treatment-emergent adverse events (TEAE) are defined as 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. A TEAE may also be a pretreatment adverse event or a concurrent medical condition diagnosed prior to the date of first dose of study drug that increases in severity after the start of dosing.
Secondary outcomes
- Change From Baseline in Glycosylated Hemoglobin (Week 8). [Baseline and 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.
- Change From Baseline in Glycosylated Hemoglobin (Week 12). [Baseline and 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 and glycosylated hemoglobin collected at baseline.
- Change From Baseline in Glycosylated Hemoglobin (Week 16). [Baseline and Week 16.]: 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 16 and glycosylated hemoglobin collected at baseline.
- Change From Baseline in Glycosylated Hemoglobin (Week 20). [Baseline and Week 20.]: 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 20 and glycosylated hemoglobin collected at baseline.
- Change From Baseline in Glycosylated Hemoglobin (Week 24). [Baseline and Week 24.]: 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 24 and glycosylated hemoglobin collected at baseline.
- Change From Baseline in Glycosylated Hemoglobin (Week 28). [Baseline and Week 28.]: 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 28 and glycosylated hemoglobin collected at baseline.
- Change From Baseline in Glycosylated Hemoglobin (Week 32). [Baseline and Week 32.]: 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 32 and glycosylated hemoglobin collected at baseline.
- Change From Baseline in Glycosylated Hemoglobin (Week 36). [Baseline and Week 36.]: 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 36 and glycosylated hemoglobin collected at baseline.
- Change From Baseline in Glycosylated Hemoglobin (Week 40). [Baseline and Week 40.]: 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 40 and glycosylated hemoglobin collected at baseline.
- Change From Baseline in Glycosylated Hemoglobin (Week 44). [Baseline and Week 44.]: 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 44 and glycosylated hemoglobin collected at baseline.
- Change From Baseline in Glycosylated Hemoglobin (Week 48). [Baseline and Week 48.]: 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 48 and glycosylated hemoglobin collected at baseline.
- Change From Baseline in Glycosylated Hemoglobin (Week 52). [Baseline and Week 52.]: 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 52 and glycosylated hemoglobin collected at baseline.
- Change From Baseline in Glycosylated Hemoglobin (Final Visit). [Baseline and Final Visit (up to 52).]: 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 final visit and glycosylated hemoglobin collected at baseline.
- Change From Baseline in Fasting Blood Glucose (Week 8). [Baseline and Week 8.]: The change between the value of fasting blood glucose collected at week 8 and baseline.
- Change From Baseline in Fasting Blood Glucose (Week 12). [Baseline and Week 12.]: The change between the value of fasting blood glucose collected at week 12 and baseline.
- Change From Baseline in Fasting Blood Glucose (Week 16). [Baseline and Week 16.]: The change between the value of fasting blood glucose collected at week 6 and baseline.
- Change From Baseline in Fasting Blood Glucose (Week 20). [Baseline and Week 20.]: The change between the value of fasting blood glucose collected at week 20 and baseline.
- Change From Baseline in Fasting Blood Glucose (Week 24). [Baseline and Week 24.]: The change between the value of fasting blood glucose collected at week 24 and baseline.
- Change From Baseline in Fasting Blood Glucose (Week 28). [Baseline and Week 28.]: The change between the value of fasting blood glucose collected at week 28 and baseline.
- Change From Baseline in Fasting Blood Glucose (Week 32). [Baseline and Week 32.]: The change between the value of fasting blood glucose collected at week 32 and baseline.
- Change From Baseline in Fasting Blood Glucose (Week 36). [Baseline and Week 36.]: The change between the value of fasting blood glucose collected at week 36 and baseline.
- Change From Baseline in Fasting Blood Glucose (Week 40). [Baseline and Week 40.]: The change between the value of fasting blood glucose collected at week 40 and baseline.
- Change From Baseline in Fasting Blood Glucose (Week 44). [Baseline and Week 44.]: The change between the value of fasting blood glucose collected at week 44 and baseline.
- Change From Baseline in Fasting Blood Glucose (Week 48). [Baseline and Week 48.]: The change between the value of fasting blood glucose collected at week 48 and baseline.
- Change From Baseline in Fasting Blood Glucose (Week 52). [Baseline and Week 52.]: The change between the value of fasting blood glucose collected at week 52 and baseline.
- Change From Baseline in Fasting Blood Glucose (Final Visit). [Baseline and Final Visit (up to Week 52).]: The change between the value of fasting blood glucose collected at final visit and baseline.
- Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Week 12). [Baseline and Week 12.]: The change between the value of blood glucose measured by the meal tolerance test collected at week 12 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.
- Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Week 24). [Baseline and Week 24.]: The change between the value of blood glucose measured by the meal tolerance test collected at week 24 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.
- Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Week 52). [Baseline and Week 52.]: The change between the value of blood glucose measured by the meal tolerance test collected at week 52 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.
- Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Final Visit). [Baseline and Final Visit (up to Week 52).]: The change between the value of blood glucose measured by the meal tolerance test collected at 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.
+Eligibility
Sex: All, ages: 20 Years to 64 Years
Inclusion Criteria:
Common criteria that applied to participants completing both the core phase 2/3 sulfonylurea add-on study and those completing the core phase 2/3 metformin add-on study:
1. Had completed the core phase 2/3 sulfonylurea add-on study or the core phase 2/3 metformin add-on study.
2. Was capable of understanding and complying with protocol requirements.
3. Signed a written informed consent form prior to the initiation of any study procedure.
Exclusion Criteria:
Common criteria that applied to participants completing both the core phase 2/3 sulfonylurea add-on study and those completing the core phase 2/3 metformin add-on study:
1. With clinical manifestation of hepatic impairment (eg, an aspartate aminotransferase or alanine aminotransferase value of 2.5 times or more of the upper reference limit at Week 8 of the core phase 2/3 sulfonylurea add-on study or the core phase 2/3 metformin add-on study).
2. With clinical manifestation of renal impairment (eg, a creatinine value of 1.5 times or more of the upper reference limit at Week 8 of the core phase 2/3 sulfonylurea add-on study or the core phase 2/3 metformin add-on study).
3. With serious cardiac disease, cerebrovascular disorder, or serious pancreatic or hematological disease (eg, a subject who requires hospital admission).
Criteria that applied only to participants completing the core phase 2/3 metformin add-on study:
1\. With history or symptoms of lactic acidosis.
+Posted results
Participant flow
| Milestone | CCT/005 - 12.5 mg Dose Group* → 12.5 mg Combination Group | CCT/005 - 25 mg Dose Group* → 25 mg Combination Dose Group | Glimepiride Monotherapy Group* → 12.5 mg Combination Group | Glimepiride Monotherapy Group* → 25 mg Combination Group | CCT/006 - 12.5 mg Dose Group* → 12.5 mg Combination Group | CCT/006 - 25 mg Dose Group* → 25 mg Combination Group | Metformin Monotherapy Group* → 12.5 mg Combination Group | Metformin Monotherapy Group* → 25 mg Combination Group |
|---|
| Started | 99 | 102 | 46 | 49 | 91 | 90 | 50 | 49 |
| Completed | 97 | 102 | 46 | 49 | 91 | 90 | 50 | 49 |
| Not completed | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Outcome results
- Number of Participants With Adverse Events. (Primary), Number, participants: Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID 16; Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID 3; Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID 7; Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID 5
- Change From Baseline in Glycosylated Hemoglobin (Week 8). (Secondary), Mean, percentage of Glycosylated Hemoglobin: Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID -0.53 +/- 0.506; Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID -0.65 +/- 0.515; Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID -0.53 +/- 0.486; Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID -0.59 +/- 0.394
- Change From Baseline in Glycosylated Hemoglobin (Week 12). (Secondary), Mean, percentage of Glycosylated Hemoglobin: Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID -0.63 +/- 0.626; Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID -0.72 +/- 0.589; Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID -0.61 +/- 0.576; Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID -0.71 +/- 0.489
- Change From Baseline in Glycosylated Hemoglobin (Week 16). (Secondary), Mean, percentage of Glycosylated Hemoglobin: Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID -0.66 +/- 0.685; Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID -0.76 +/- 0.660; Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID -0.69 +/- 0.614; Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID -0.78 +/- 0.495
- Change From Baseline in Glycosylated Hemoglobin (Week 20). (Secondary), Mean, percentage of Glycosylated Hemoglobin: Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID -0.63 +/- 0.754; Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID -0.70 +/- 0.689; Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID -0.67 +/- 0.648; Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID -0.78 +/- 0.553
- Change From Baseline in Glycosylated Hemoglobin (Week 24). (Secondary), Mean, percentage of Glycosylated Hemoglobin: Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID -0.59 +/- 0.823; Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID -0.70 +/- 0.740; Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID -0.68 +/- 0.668; Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID -0.78 +/- 0.623
- Change From Baseline in Glycosylated Hemoglobin (Week 28). (Secondary), Mean, percentage of Glycosylated Hemoglobin: Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID -0.62 +/- 0.841; Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID -0.76 +/- 0.721; Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID -0.70 +/- 0.659; Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID -0.84 +/- 0.596
- Change From Baseline in Glycosylated Hemoglobin (Week 32). (Secondary), Mean, percentage of Glycosylated Hemoglobin: Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID -0.63 +/- 0.868; Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID -0.77 +/- 0.736; Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID -0.67 +/- 0.644; Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID -0.81 +/- 0.634
- Change From Baseline in Glycosylated Hemoglobin (Week 36). (Secondary), Mean, percentage of Glycosylated Hemoglobin: Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID -0.64 +/- 0.881; Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID -0.77 +/- 0.745; Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID -0.67 +/- 0.659; Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID -0.79 +/- 0.653
- Change From Baseline in Glycosylated Hemoglobin (Week 40). (Secondary), Mean, percentage of Glycosylated Hemoglobin: Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID -0.66 +/- 0.799; Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID -0.74 +/- 0.779; Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID -0.63 +/- 0.676; Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID -0.74 +/- 0.698
- Change From Baseline in Glycosylated Hemoglobin (Week 44). (Secondary), Mean, percentage of Glycosylated Hemoglobin: Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID -0.48 +/- 0.726; Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID -0.71 +/- 0.666; Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID -0.47 +/- 0.787; Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID -0.70 +/- 0.688
- Change From Baseline in Glycosylated Hemoglobin (Week 48). (Secondary), Mean, percentage of Glycosylated Hemoglobin: Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID -0.40 +/- 0.706; Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID -0.61 +/- 0.660; Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID -0.36 +/- 0.762; Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID -0.62 +/- 0.707
- Change From Baseline in Glycosylated Hemoglobin (Week 52). (Secondary), Mean, percentage of Glycosylated Hemoglobin: Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID -0.33 +/- 0.652; Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID -0.53 +/- 0.643; Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID -0.29 +/- 0.744; Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID -0.53 +/- 0.790
- Change From Baseline in Glycosylated Hemoglobin (Final Visit). (Secondary), Mean, percentage of Glycosylated Hemoglobin: Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID -0.42 +/- 0.838; Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID -0.58 +/- 0.791; Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID -0.44 +/- 0.720; Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID -0.58 +/- 0.781
- Change From Baseline in Fasting Blood Glucose (Week 8). (Secondary), Mean, mg/dL: Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID -20.7 +/- 26.50; Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID -19.6 +/- 30.53; Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID -22.0 +/- 22.76; Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID -23.4 +/- 26.75
- Change From Baseline in Fasting Blood Glucose (Week 12). (Secondary), Mean, mg/dL: Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID -22.0 +/- 32.19; Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID -18.1 +/- 29.05; Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID -22.9 +/- 24.04; Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID -24.2 +/- 27.30
- Change From Baseline in Fasting Blood Glucose (Week 16). (Secondary), Mean, mg/dL: Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID -22.3 +/- 34.37; Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID -17.8 +/- 32.22; Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID -21.8 +/- 26.86; Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID -26.1 +/- 26.93
- Change From Baseline in Fasting Blood Glucose (Week 20). (Secondary), Mean, mg/dL: Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID -22.4 +/- 31.75; Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID -22.3 +/- 30.93; Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID -23.4 +/- 27.88; Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID -26.1 +/- 26.19
- Change From Baseline in Fasting Blood Glucose (Week 24). (Secondary), Mean, mg/dL: Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID -24.0 +/- 31.69; Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID -25.0 +/- 32.68; Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID -25.6 +/- 24.22; Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID -26.3 +/- 28.09
- Change From Baseline in Fasting Blood Glucose (Week 28). (Secondary), Mean, mg/dL: Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID -19.9 +/- 36.87; Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID -25.9 +/- 33.67; Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID -25.8 +/- 26.16; Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID -28.2 +/- 29.49
- 11 more outcome measures not shown.
Adverse events
Time frame: 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.
| Arm | Deaths | Serious adverse events | Other adverse events |
|---|
| Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID | 0 | 16/150 (10.7%) | 116/150 (77.3%) |
| Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID | 0 | 3/152 (2.0%) | 134/152 (88.2%) |
| Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID | 0 | 7/142 (4.9%) | 108/142 (76.1%) |
| Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID | 0 | 5/145 (3.4%) | 113/145 (77.9%) |
Serious adverse events by term
| Term | Organ system | Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID | Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID | Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID | Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID |
|---|
| Acute myocardial infarction | Cardiac disorders | 1/150 | 0/152 | 2/142 | 0/145 |
| Angina pectoris | Cardiac disorders | 1/150 | 1/152 | 0/142 | 0/145 |
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/150 | 0/0 | 0/142 | 1/145 |
| Cardiac failure | Cardiac disorders | 0/150 | 0/152 | 0/142 | 1/145 |
| Cellulitis | Infections and infestations | 1/150 | 0/152 | 0/142 | 0/145 |
| Cerebral circulatory failure | Nervous system disorders | 0/150 | 0/152 | 0/142 | 1/145 |
| Cerebral infarction | Nervous system disorders | 1/150 | 0/152 | 0/142 | 0/145 |
| Embolic stroke | Nervous system disorders | 1/150 | 0/152 | 0/142 | 0/145 |
| Enteritis infectious | Infections and infestations | 0/150 | 0/152 | 1/142 | 0/145 |
| Fall | Injury, poisoning and procedural complications | 1/150 | 0/152 | 1/142 | 0/145 |
| Gas gangrene | Infections and infestations | 1/150 | 0/152 | 0/142 | 0/145 |
| Gastric cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 2/150 | 0/152 | 0/142 | 0/145 |
| Gastritis | Gastrointestinal disorders | 1/150 | 0/152 | 0/142 | 0/145 |
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/150 | 0/0 | 0/142 | 1/145 |
| Malignant neoplasm of renal pelvis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/150 | 0/152 | 0/142 | 0/145 |
| Mallory-Weiss syndrome | Gastrointestinal disorders | 0/150 | 0/152 | 0/142 | 1/145 |
| Pancreatic carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/150 | 0/1 | 1/142 | 0/145 |
| Pneumonia legionella | Infections and infestations | 0/150 | 0/152 | 1/142 | 0/145 |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/150 | 0/152 | 0/142 | 0/145 |
| Road traffic accident | Injury, poisoning and procedural complications | 2/150 | 1/152 | 1/142 | 0/145 |
| Sciatica | Nervous system disorders | 1/150 | 0/152 | 0/142 | 0/145 |
| Sudden death | General disorders | 1/150 | 0/152 | 0/142 | 0/145 |
| Vertigo | Ear and labyrinth disorders | 0/150 | 1/152 | 0/142 | 0/145 |
Other adverse events by term
| Term | Organ system | Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID | Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID | Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID | Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID |
|---|
| Alanine aminotransferase increased | Investigations | 0/150 | 0/152 | 6/142 | 2/145 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 6/150 | 4/152 | 2/142 | 6/145 |
| Back pain | Musculoskeletal and connective tissue disorders | 8/150 | 11/152 | 9/142 | 6/145 |
| Blood creatine phosphokinase increased | Investigations | 2/150 | 5/152 | 0/142 | 0/145 |
| Bronchitis | Infections and infestations | 0/150 | 0/152 | 1/142 | 6/145 |
| Cataract | Eye disorders | 6/150 | 7/152 | 0/142 | 0/145 |
| Chest pain | General disorders | 1/150 | 5/152 | 0/142 | 0/145 |
| Conjunctivitis allergic | Eye disorders | 0/150 | 0/152 | 1/142 | 6/145 |
| Constipation | Gastrointestinal disorders | 7/150 | 7/152 | 7/142 | 8/145 |
| Cystitis | Infections and infestations | 5/150 | 5/152 | 5/142 | 4/145 |
| Dental caries | Gastrointestinal disorders | 6/150 | 1/152 | 1/142 | 7/145 |
| Diabetic retinopathy | Eye disorders | 4/150 | 8/152 | 6/142 | 10/145 |
| Diarrhoea | Gastrointestinal disorders | 5/150 | 3/152 | 6/142 | 3/145 |
| Eczema | Skin and subcutaneous tissue disorders | 0/150 | 0/152 | 7/142 | 6/145 |
| Fall | Injury, poisoning and procedural complications | 7/150 | 12/152 | 0/142 | 0/145 |
| Gastritis | Gastrointestinal disorders | 4/150 | 8/152 | 0/142 | 0/145 |
| Gastroenteritis | Infections and infestations | 7/150 | 4/152 | 0/142 | 0/145 |
| Headache | Nervous system disorders | 0/150 | 0/152 | 9/142 | 3/145 |
| Hepatic steatosis | Hepatobiliary disorders | 0/150 | 0/152 | 2/142 | 5/145 |
| Hypertension | Vascular disorders | 0/150 | 0/152 | 7/142 | 4/145 |
| Hypoglycaemia | Metabolism and nutrition disorders | 4/150 | 8/152 | 0/142 | 0/145 |
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | 0/150 | 0/152 | 1/142 | 5/145 |
| Nasopharyngitis | Infections and infestations | 46/150 | 57/152 | 44/142 | 53/145 |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | 6/150 | 1/152 | 0/142 | 0/145 |
| Periarthritis | Musculoskeletal and connective tissue disorders | 7/150 | 4/152 | 0/142 | 0/145 |
| Upper respiratory tract inflammation | Respiratory, thoracic and mediastinal disorders | 10/150 | 16/152 | 6/142 | 6/145 |
| Urticaria | Skin and subcutaneous tissue disorders | 2/150 | 5/152 | 0/142 | 0/145 |
| White blood cell count increased | Investigations | 0/150 | 0/152 | 3/142 | 5/145 |
+Publications
- Results publication: Seino Y, Hiroi S, Hirayama M, Kaku K. Efficacy and safety of alogliptin added to sulfonylurea in Japanese patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial with an open-label, long-term extension study. J Diabetes Investig. 2012 Dec 20;3(6):517-25. doi: 10.1111/j.2040-1124.2012.00226.x. Epub 2012 Jul 12. PMID 24843617
+Investigators
- Professor, Diabetes and Endocrine Division, Study director, Department of Medicine, Kawasaki Medical School