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

A Long-Term, Open-Label Extension Study to Investigate the Long-Term Safety of SYR-322 When Used in Combination With Thiazolidine in Subjects With Type 2 Diabetes in Japan

Status

Completed

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01318122

Enrollment

336

Registered

2011-03-18

Start date

2008-05-31

Completion date

2009-08-31

Last updated

2012-02-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type 2 Diabetes Mellitus

Keywords

Diabetes Mellitus - Type 2, Diabetes Mellitus, Drug Therapy

Brief summary

The purpose of this study was to evaluate the long-term safety and efficacy of alogliptin and Thiazolidine administered once daily (QD) for 40 consecutive weeks in participants who completed a phase 2/3 Thiazolidine add on study.

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. To evaluate the long-term safety and efficacy of alogliptin, participants in the present study were enrolled from a core phase 2/3 thiazolidine add on study (SYR-322/CCT-004; NCT01318070).

Interventions

DRUGAlogliptin and pioglitazone

Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

33 Years to 88 Years

Healthy volunteers

Inclusion criteria

1. Had completed the core phase 2/3 thiazolidine add on study. 2. The subject 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

1. With clinical manifestation of hepatic impairment (e.g., an AST or ALT value of 2.5 times or more of the upper reference limit at Week 8 of the core phase 2/3 thiazolidine add on study). 2. With clinical manifestation of renal impairment (e.g., a creatinine value of 2 mg/dL or more at Week 8 of the core phase 2/3 thiazolidine add on study). 3. With a history or symptoms of cardiac failure.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Adverse Events.	52 Weeks.	Treatment-emergent adverse events (TEAE) are adverse events with an onset that occurs after receiving study drug and within 30 days after receiving the last dose of study drug. A TEAE may also be a pre-treatment 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

Measure	Time frame	Description
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 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 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 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 Glycosylated Hemoglobin (Final Visit).	Baseline and Final Visit (up to 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 or 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 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 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 week 52 or 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 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.
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 week 52 or end of study 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 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.

Participant flow

Recruitment details

Participants enrolled at 32 investigative sites in Japan from 10 May 2008 to 03 August 2009.

Pre-assignment details

Participants who had completed the core phase 2/3 thiazolidine add on study (SYR-322/CCT-004; NCT01318070) were enrolled in one of 2, once-daily (QD) treatment groups.

Participants by arm

Arm	Count
Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	166
Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	165
Total	331

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Enrolled - Long-Term Extension Study	Adverse Event	0	0	2	1
Enrolled - Long-Term Extension Study	Other	1	0	0	0
Entered - Long-Term Extension Study	Adverse Event	6	6	2	4
Entered - Long-Term Extension Study	Lack of Efficacy	0	2	3	0
Entered - Long-Term Extension Study	Lost to Follow-up	1	0	0	0
Entered - Long-Term Extension Study	Withdrawal by Subject	2	3	1	0

Baseline characteristics

Characteristic	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD	Total
Age, Customized ≤ 64 years	116 participants	103 participants	219 participants
Age, Customized ≥ 65 years	50 participants	62 participants	112 participants
Sex: Female, Male Female	65 Participants	58 Participants	123 Participants
Sex: Female, Male Male	101 Participants	107 Participants	208 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	143 / 166	146 / 165
serious Total, serious adverse events	14 / 166	11 / 165

Outcome results

Primary

Number of Participants With Adverse Events.

Treatment-emergent adverse events (TEAE) are adverse events with an onset that occurs after receiving study drug and within 30 days after receiving the last dose of study drug. A TEAE may also be a pre-treatment 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.

Time frame: 52 Weeks.

Population: Full Analysis Set was defined as the population of participants randomized in the core phase 2/3 thiazolidine add on study (SYR-322/CCT-004 study; NCT01318070) and received at least 1 dose of the investigational products (SYR-322DB in combination with pioglitazone) for the treatment period.

Arm	Measure	Group	Value (NUMBER)
Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Number of Participants With Adverse Events.	Number of Participants with Serious Adverse Event	14 participants
Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Number of Participants With Adverse Events.	Number of Participants with Other Adverse Event	143 participants
Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD	Number of Participants With Adverse Events.	Number of Participants with Serious Adverse Event	11 participants
Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD	Number of Participants With Adverse Events.	Number of Participants with Other Adverse Event	146 participants

Secondary

Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Final Visit).

The change between the value of blood glucose measured by the meal tolerance test collected at week 52 or end of study 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.

Time frame: Baseline and Final Visit (up to Week 52).