Clinical trial NCT01318135: Long-term Safety Study of Alogliptin Used in Combination With Sulfonylurea or Metformin in Participants With Type 2 Diabetes in Japan
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Type 2 Diabetes Mellitus
Keywords: Diabetes Mellitus - Type 2
Diabetes Mellitus
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-03-18
Enrollment: 576
Sex: ALL
Minimum age (years): 20
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Number of Participants With Adverse Events.
timeFrame: 52 Weeks.
Secondary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (Week 8).
timeFrame: Baseline and Week 8.
measure: Change From Baseline in Glycosylated Hemoglobin (Week 12).
timeFrame: Baseline and Week 12.
measure: Change From Baseline in Glycosylated Hemoglobin (Week 16).
timeFrame: Baseline and Week 16.
measure: Change From Baseline in Glycosylated Hemoglobin (Week 20).
timeFrame: Baseline and Week 20.
measure: Change From Baseline in Glycosylated Hemoglobin (Week 24).
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Glycosylated Hemoglobin (Week 28).
timeFrame: Baseline and Week 28.
measure: Change From Baseline in Glycosylated Hemoglobin (Week 32).
timeFrame: Baseline and Week 32.
measure: Change From Baseline in Glycosylated Hemoglobin (Week 36).
timeFrame: Baseline and Week 36.
measure: Change From Baseline in Glycosylated Hemoglobin (Week 40).
timeFrame: Baseline and Week 40.
measure: Change From Baseline in Glycosylated Hemoglobin (Week 44).
timeFrame: Baseline and Week 44.
measure: Change From Baseline in Glycosylated Hemoglobin (Week 48).
timeFrame: Baseline and Week 48.
measure: Change From Baseline in Glycosylated Hemoglobin (Week 52).
timeFrame: Baseline and Week 52.
measure: Change From Baseline in Glycosylated Hemoglobin (Final Visit).
timeFrame: Baseline and Final Visit (up to 52).
measure: Change From Baseline in Fasting Blood Glucose (Week 8).
timeFrame: Baseline and Week 8.
measure: Change From Baseline in Fasting Blood Glucose (Week 12).
timeFrame: Baseline and Week 12.
measure: Change From Baseline in Fasting Blood Glucose (Week 16).
timeFrame: Baseline and Week 16.
measure: Change From Baseline in Fasting Blood Glucose (Week 20).
timeFrame: Baseline and Week 20.
measure: Change From Baseline in Fasting Blood Glucose (Week 24).
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Fasting Blood Glucose (Week 28).
timeFrame: Baseline and Week 28.
measure: Change From Baseline in Fasting Blood Glucose (Week 32).
timeFrame: Baseline and Week 32.
measure: Change From Baseline in Fasting Blood Glucose (Week 36).
timeFrame: Baseline and Week 36.
measure: Change From Baseline in Fasting Blood Glucose (Week 40).
timeFrame: Baseline and Week 40.
measure: Change From Baseline in Fasting Blood Glucose (Week 44).
timeFrame: Baseline and Week 44.
measure: Change From Baseline in Fasting Blood Glucose (Week 48).
timeFrame: Baseline and Week 48.
measure: Change From Baseline in Fasting Blood Glucose (Week 52).
timeFrame: Baseline and Week 52.
measure: Change From Baseline in Fasting Blood Glucose (Final Visit).
timeFrame: Baseline and Final Visit (up to Week 52).
measure: Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Week 12).
timeFrame: Baseline and Week 12.
measure: Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Week 24).
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Week 52).
timeFrame: Baseline and Week 52.
measure: Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Final Visit).
timeFrame: Baseline and Final Visit (up to Week 52).
Other outcomes:
Locations:
Study officials:
affiliation: Department of Medicine, Kawasaki Medical School
name: Professor, Diabetes and Endocrine Division
role: STUDY_DIRECTOR
References:
citation: 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.