Type 2 Diabetes
Conditions
Keywords
insulin resistance
Brief summary
The purpose of this study is to evaluate the efficacy and safety and to determine the appropriate dose for phase 3 confirmatory trial, of MP-513 (Teneligliptin) in patients with type 2 Diabetes based on the change of HbA1c and adverse events after 12 weeks administration once daily in multi-center, randomized, double-blind, placebo-controlled, parallel assignment manner.
Interventions
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 6.5 - 9.5% * Patients who were not administered 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 failure, or secondary diabetes (Cushing disease, acromegaly, etc) * Patients with Class III/IV heart failure symptoms according to New York Heart Association (NYHA) functional classification * Patients with serious diabetic complications * Patients who are habitual excessive alcohol consumption. * Patients with severe hepatic disorder or severe renal disorder. * 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 | 12 weeks | 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 | 12 weeks | 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 2-hour Postprandial Plasma Glucose at Week 12 | 12 weeks | 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. |
| Change From Baseline in the Areas Under the Curve From 0 to 2 h (AUC0-2h) for Postprandial Plasma Glucose at Week 12 | 12 weeks | 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. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Teneligliptin placebo-matching tablets, orally, once daily | 80 |
| Teneligliptin 10 mg Teneligliptin 10 mg, orally, once daily | 84 |
| Teneligliptin 20 mg Teneligliptin 20 mg, orally, once daily | 79 |
| Teneligliptin 40 mg Teneligliptin 40 mg, orally, once daily | 81 |
| Total | 324 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 1 | 2 |
| Overall Study | Physician Decision | 1 | 1 | 2 | 3 |
Baseline characteristics
| Characteristic | Placebo | Teneligliptin 10 mg | Teneligliptin 20 mg | Teneligliptin 40 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 58.5 years STANDARD_DEVIATION 9.6 | 57.7 years STANDARD_DEVIATION 9.1 | 59.2 years STANDARD_DEVIATION 9.5 | 57.5 years STANDARD_DEVIATION 10.4 | 58.2 years STANDARD_DEVIATION 9.6 |
| Sex: Female, Male Female | 29 Participants | 34 Participants | 20 Participants | 28 Participants | 111 Participants |
| Sex: Female, Male Male | 51 Participants | 50 Participants | 59 Participants | 53 Participants | 213 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 | 44 / 80 | 50 / 84 | 40 / 79 | 46 / 81 |
| serious Total, serious adverse events | 1 / 80 | 0 / 84 | 0 / 79 | 0 / 81 |
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: 12 weeks
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 | Change From Baseline in HbA1c at Week 12 | 0.11 Percent | Standard Error 0.05 |
| Teneligliptin 10 mg | Change From Baseline in HbA1c at Week 12 | -0.77 Percent | Standard Error 0.05 |
| Teneligliptin 20 mg | Change From Baseline in HbA1c at Week 12 | -0.80 Percent | Standard Error 0.05 |
| Teneligliptin 40 mg | Change From Baseline in HbA1c at Week 12 | -0.91 Percent | Standard Error 0.05 |
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: 12 weeks
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 | Change From Baseline in 2-hour Postprandial Plasma Glucose at Week 12 | 7.3 mg / dL | Standard Error 4.5 |
| Teneligliptin 10 mg | Change From Baseline in 2-hour Postprandial Plasma Glucose at Week 12 | -43.3 mg / dL | Standard Error 4.3 |
| Teneligliptin 20 mg | Change From Baseline in 2-hour Postprandial Plasma Glucose at Week 12 | -49.4 mg / dL | Standard Error 4.5 |
| Teneligliptin 40 mg | Change From Baseline in 2-hour Postprandial Plasma Glucose at Week 12 | -51.3 mg / dL | Standard Error 4.5 |
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: 12 weeks
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 | Change From Baseline in Fasting Plasma Glucose at Week 12 | 2.8 mg / dL | Standard Error 2 |
| Teneligliptin 10 mg | Change From Baseline in Fasting Plasma Glucose at Week 12 | -15.0 mg / dL | Standard Error 2 |
| Teneligliptin 20 mg | Change From Baseline in Fasting Plasma Glucose at Week 12 | -14.1 mg / dL | Standard Error 2.1 |
| Teneligliptin 40 mg | Change From Baseline in Fasting Plasma Glucose at Week 12 | -17.2 mg / dL | Standard Error 2 |
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: 12 weeks
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 | Change From Baseline in the Areas Under the Curve From 0 to 2 h (AUC0-2h) for Postprandial Plasma Glucose at Week 12 | 5.897 mg*h / dL | Standard Error 6.41 |
| Teneligliptin 10 mg | Change From Baseline in the Areas Under the Curve From 0 to 2 h (AUC0-2h) for Postprandial Plasma Glucose at Week 12 | -65.445 mg*h / dL | Standard Error 6.141 |
| Teneligliptin 20 mg | Change From Baseline in the Areas Under the Curve From 0 to 2 h (AUC0-2h) for Postprandial Plasma Glucose at Week 12 | -73.211 mg*h / dL | Standard Error 6.409 |
| Teneligliptin 40 mg | Change From Baseline in the Areas Under the Curve From 0 to 2 h (AUC0-2h) for Postprandial Plasma Glucose at Week 12 | -75.326 mg*h / dL | Standard Error 6.422 |