Type 2 Diabetes Mellitus
Conditions
Keywords
insulin resistance
Brief summary
The purpose of this study is to evaluate the efficacy and safety of MP-513 (Teneligliptin) in combination with thiazolidinedione (pioglitazone) in patients with type 2 Diabetes for 12 weeks administration and to evaluate the safety and efficacy of MP-513 in combination with thiazolidinedione with an extension treatment for up to 52 weeks.
Interventions
DRUGPlacebo / Teneli (Teneligliptin) + pio (pioglitazone)
Placebo for 12 weeks (double-blind period) followed by teneligliptin for an additional 40 weeks (open-label period) in combination with pioglitazone.
DRUGTeneli / Teneli + pio
Teneligliptin for 12 weeks (double-blind period) followed by teneligliptin for an additional 40 weeks (open-label period) in combination with pioglitazone.
Sponsors
Tanabe Pharma Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients who are 20 - 75 years old * Patients who are under dietary management and taking therapeutic exercise for diabetes over 12 weeks before administration of investigational drug * Patients whose HbA1c is between 6.5% and 10.0% * Patients who took Thiazolidinedione for diabetes over 16 weeks before administration of investigational drug * Patients who were not administered diabetes therapeutic drugs prohibited for concomitant use within 12 weeks before administration of investigational drug.
Exclusion criteria
* Patients with type 1 diabetes, diabetes mellitus caused by pancreas impairment, or secondary diabetes (Cushing disease, acromegaly, etc) * Patients who are accepting treatments of arrhythmias * Patients with serious diabetic complications * Patients who are the excessive alcohol addicts * Patients with severe hepatic disorder or severe renal disorder. * Patients who are pregnant, lactating, and probably pregnant patients, and patients who can not agree to contraception
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c at Week 12 | at Week 0 and Week 12 | The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Week 12. Least squares means were derived from an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline HbA1c as a covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose at Week 12 | at Week 0 and Week 12 | The change from Baseline in Fasting Plasma Glucose collected at Week 12. Least squares means were derived from an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline Fasting Plasma Glucose as a covariate. |
| Change From Baseline in the Areas Under the Curve From 0 to 2 h (AUC0-2h) for Postprandial Plasma Glucose at Week 12 | 0, 0.5, 1, 2 hours post-dose at Week 0 and Week 12 | The change from Baseline in AUC0-2h for Postprandial Plasma Glucose collected at Week 12. Least squares means were derived from an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline AUC0-2h for Postprandial Plasma Glucose as a covariate. |
| Change From Baseline in 2-hour Postprandial Plasma Glucose at Week 12 | at Week 0 and Week 12 | The change from Baseline in 2-hour Postprandial Plasma Glucose collected at Week 12. Least squares means were derived from an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline 2-hour Postprandial Plasma Glucose as a covariate. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo/Teneli + Pio Placebo for 12 weeks (double-blind period) followed by teneligliptin for an additional 40 weeks (open-label period) in combination with pioglitazone. | 101 |
| Teneli/Teneli + Pio Teneligliptin for 12 weeks (double-blind period) followed by teneligliptin for an additional 40 weeks (open-label period) in combination with pioglitazone. | 103 |
| Total | 204 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1：Double Blind Period | Adverse Event | 2 | 1 |
| Period 1：Double Blind Period | Lack of Efficacy | 1 | 0 |
| Period 1：Double Blind Period | Physician Decision | 0 | 4 |
| Period 2：Open-label Period | Adverse Event | 4 | 5 |
| Period 2：Open-label Period | Physician Decision | 3 | 1 |
| Period 2：Open-label Period | Withdrawal by Subject | 0 | 4 |
Baseline characteristics
| Characteristic | Placebo/Teneli + Pio | Teneli/Teneli + Pio | Total |
|---|---|---|---|
| Age, Continuous | 61.1 years STANDARD_DEVIATION 8.9 | 59.7 years STANDARD_DEVIATION 9.7 | 60.4 years STANDARD_DEVIATION 9.3 |
| Sex: Female, Male Female | 25 Participants | 35 Participants | 60 Participants |
| Sex: Female, Male Male | 76 Participants | 68 Participants | 144 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 47 / 101 | 63 / 103 | 89 / 98 | 88 / 103 |
| serious Total, serious adverse events | 1 / 101 | 4 / 103 | 3 / 98 | 11 / 103 |
Outcome results
Primary
Change From Baseline in HbA1c at Week 12
The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Week 12. Least squares means were derived from an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline HbA1c as a covariate.
Time frame: at Week 0 and Week 12
Population: The full analysis set, consisting of all type 2 diabetic patients, who received at least one dose of study drug and who had at least one efficacy data after randomization. Analysis based on last observation carried forward, where the last postbaseline double-blind observed value was carried forward and used for Week 12 where data was missing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Teneli + Pio | Change From Baseline in HbA1c at Week 12 | -0.20 Percent of HbA1c | Standard Error 0.05 |
| Teneli/Teneli + Pio | Change From Baseline in HbA1c at Week 12 | -0.94 Percent of HbA1c | Standard Error 0.04 |
Secondary
Change From Baseline in 2-hour Postprandial Plasma Glucose at Week 12
The change from Baseline in 2-hour Postprandial Plasma Glucose collected at Week 12. Least squares means were derived from an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline 2-hour Postprandial Plasma Glucose as a covariate.
Time frame: at Week 0 and Week 12
Population: The full analysis set, consisting of all type 2 diabetic patients, who received at least one dose of study drug and who had at least one efficacy data after randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Teneli + Pio | Change From Baseline in 2-hour Postprandial Plasma Glucose at Week 12 | -5.6 mg / dL | Standard Error 3.6 |
| Teneli/Teneli + Pio | Change From Baseline in 2-hour Postprandial Plasma Glucose at Week 12 | -56.9 mg / dL | Standard Error 3.6 |
Secondary
Change From Baseline in Fasting Plasma Glucose at Week 12
The change from Baseline in Fasting Plasma Glucose collected at Week 12. Least squares means were derived from an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline Fasting Plasma Glucose as a covariate.
Time frame: at Week 0 and Week 12
Population: The full analysis set, consisting of all type 2 diabetic patients, who received at least one dose of study drug and who had at least one efficacy data after randomization. Analysis based on last observation carried forward, where the last postbaseline double-blind observed value was carried forward and used for Week 12 where data was missing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Teneli + Pio | Change From Baseline in Fasting Plasma Glucose at Week 12 | -4.5 mg / dL | Standard Error 2 |
| Teneli/Teneli + Pio | Change From Baseline in Fasting Plasma Glucose at Week 12 | -21.0 mg / dL | Standard Error 1.9 |
Secondary
Change From Baseline in the Areas Under the Curve From 0 to 2 h (AUC0-2h) for Postprandial Plasma Glucose at Week 12
The change from Baseline in AUC0-2h for Postprandial Plasma Glucose collected at Week 12. Least squares means were derived from an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline AUC0-2h for Postprandial Plasma Glucose as a covariate.
Time frame: 0, 0.5, 1, 2 hours post-dose at Week 0 and Week 12
Population: The full analysis set, consisting of all type 2 diabetic patients, who received at least one dose of study drug and who had at least one efficacy data after randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Teneli + Pio | Change From Baseline in the Areas Under the Curve From 0 to 2 h (AUC0-2h) for Postprandial Plasma Glucose at Week 12 | -13.722 mg*h / dL | Standard Error 5.134 |
| Teneli/Teneli + Pio | Change From Baseline in the Areas Under the Curve From 0 to 2 h (AUC0-2h) for Postprandial Plasma Glucose at Week 12 | -85.031 mg*h / dL | Standard Error 5.134 |