Long-term Safety Study of Alogliptin Used in Combination With Sulfonylurea or Metformin in Participants With Type 2 Diabetes in Japan

Overview[ - collapse ][ - ]

Purpose 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).
ConditionType 2 Diabetes Mellitus
InterventionDrug: Alogliptin and glimepiride
Drug: Alogliptin and glimepiride
Drug: Alogliptin and metformin
Drug: Alogliptin and metformin
PhasePhase 2/Phase 3
SponsorTakeda
Responsible PartyTakeda
ClinicalTrials.gov IdentifierNCT01318135
First ReceivedMarch 16, 2011
Last UpdatedJuly 7, 2012
Last verifiedJuly 2012

Tracking Information[ + expand ][ + ]

First Received DateMarch 16, 2011
Last Updated DateJuly 7, 2012
Start DateJanuary 2009
Estimated Primary Completion DateApril 2010
Current Primary Outcome MeasuresNumber of Participants With Adverse Events. [Time Frame: 52 Weeks.] [Designated as safety issue: Yes]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.
Current Secondary Outcome Measures
  • Change From Baseline in Glycosylated Hemoglobin (Week 8). [Time Frame: Baseline and Week 8.] [Designated as safety issue: No]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). [Time Frame: Baseline and Week 12.] [Designated as safety issue: No]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). [Time Frame: Baseline and Week 16.] [Designated as safety issue: No]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). [Time Frame: Baseline and Week 20.] [Designated as safety issue: No]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). [Time Frame: Baseline and Week 24.] [Designated as safety issue: No]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). [Time Frame: Baseline and Week 28.] [Designated as safety issue: No]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). [Time Frame: Baseline and Week 32.] [Designated as safety issue: No]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). [Time Frame: Baseline and Week 36.] [Designated as safety issue: No]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). [Time Frame: Baseline and Week 40.] [Designated as safety issue: No]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). [Time Frame: Baseline and Week 44.] [Designated as safety issue: No]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). [Time Frame: Baseline and Week 48.] [Designated as safety issue: No]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). [Time Frame: Baseline and Week 52.] [Designated as safety issue: No]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). [Time Frame: Baseline and Final Visit (up to 52).] [Designated as safety issue: No]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). [Time Frame: Baseline and Week 8.] [Designated as safety issue: No]The change between the value of fasting blood glucose collected at week 8 and baseline.
  • Change From Baseline in Fasting Blood Glucose (Week 12). [Time Frame: Baseline and Week 12.] [Designated as safety issue: No]The change between the value of fasting blood glucose collected at week 12 and baseline.
  • Change From Baseline in Fasting Blood Glucose (Week 16). [Time Frame: Baseline and Week 16.] [Designated as safety issue: No]The change between the value of fasting blood glucose collected at week 6 and baseline.
  • Change From Baseline in Fasting Blood Glucose (Week 20). [Time Frame: Baseline and Week 20.] [Designated as safety issue: No]The change between the value of fasting blood glucose collected at week 20 and baseline.
  • Change From Baseline in Fasting Blood Glucose (Week 24). [Time Frame: Baseline and Week 24.] [Designated as safety issue: No]The change between the value of fasting blood glucose collected at week 24 and baseline.
  • Change From Baseline in Fasting Blood Glucose (Week 28). [Time Frame: Baseline and Week 28.] [Designated as safety issue: No]The change between the value of fasting blood glucose collected at week 28 and baseline.
  • Change From Baseline in Fasting Blood Glucose (Week 32). [Time Frame: Baseline and Week 32.] [Designated as safety issue: No]The change between the value of fasting blood glucose collected at week 32 and baseline.
  • Change From Baseline in Fasting Blood Glucose (Week 36). [Time Frame: Baseline and Week 36.] [Designated as safety issue: No]The change between the value of fasting blood glucose collected at week 36 and baseline.
  • Change From Baseline in Fasting Blood Glucose (Week 40). [Time Frame: Baseline and Week 40.] [Designated as safety issue: No]The change between the value of fasting blood glucose collected at week 40 and baseline.
  • Change From Baseline in Fasting Blood Glucose (Week 44). [Time Frame: Baseline and Week 44.] [Designated as safety issue: No]The change between the value of fasting blood glucose collected at week 44 and baseline.
  • Change From Baseline in Fasting Blood Glucose (Week 48). [Time Frame: Baseline and Week 48.] [Designated as safety issue: No]The change between the value of fasting blood glucose collected at week 48 and baseline.
  • Change From Baseline in Fasting Blood Glucose (Week 52). [Time Frame: Baseline and Week 52.] [Designated as safety issue: No]The change between the value of fasting blood glucose collected at week 52 and baseline.
  • Change From Baseline in Fasting Blood Glucose (Final Visit). [Time Frame: Baseline and Final Visit (up to Week 52).] [Designated as safety issue: No]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). [Time Frame: Baseline and Week 12.] [Designated as safety issue: No]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). [Time Frame: Baseline and Week 24.] [Designated as safety issue: No]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). [Time Frame: Baseline and Week 52.] [Designated as safety issue: No]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). [Time Frame: Baseline and Final Visit (up to Week 52).] [Designated as safety issue: No]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.

Descriptive Information[ + expand ][ + ]

Brief TitleLong-term Safety Study of Alogliptin Used in Combination With Sulfonylurea or Metformin in Participants With Type 2 Diabetes in Japan
Official TitleA 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
Brief 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).
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).
Study TypeInterventional
Study PhasePhase 2/Phase 3
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionType 2 Diabetes Mellitus
InterventionDrug: Alogliptin and glimepiride
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.
Other Names:
  • SYR-322
  • Amaryl
Drug: Alogliptin and glimepiride
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.
Other Names:
  • SYR-322
  • Amaryl
Drug: Alogliptin and metformin
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.
Other Names:
  • SYR-322
  • Glycoran
Drug: Alogliptin and metformin
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.
Other Names:
  • SYR-322
  • Glycoran
Study Arm (s)
  • Active Comparator: Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID
  • Active Comparator: Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID
  • Active Comparator: Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID
  • Active Comparator: Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment576
Estimated Completion DateApril 2010
Estimated Primary Completion DateJanuary 2010
Eligibility Criteria
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.
GenderBoth
Ages20 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesNot Provided

Administrative Information[ + expand ][ + ]

NCT Number NCT01318135
Other Study ID NumbersSYR-322/OCT-005
Has Data Monitoring CommitteeNo
Information Provided ByTakeda
Study SponsorTakeda
CollaboratorsNot Provided
Investigators Study Director: Professor, Diabetes and Endocrine Division Department of Medicine, Kawasaki Medical School
Verification DateJuly 2012