Type 2 Diabetes Mellitus
Conditions
Keywords
insulin resistance
Brief summary
The purpose of this study is to evaluate the efficacy and safety of Teneligliptin in combination with Insulin in patients with type 2 Diabetes for 16 weeks administration and to evaluate the safety and efficacy of Teneligliptin in combination with Insulin with an extension treatment for up to 52 weeks.
Interventions
DRUGTeneli (Teneligliptin)
DRUGPlacebo
DRUGInsulin
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who has been receiving a stable dose and regimen of insulin over 12 weeks before administration of investigational drug * 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 7.5% and 10.5% * 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 0 and Week 16 | 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 16. 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 0 and Week 16 | The change from Baseline in Fasting Plasma Glucose collected at Week 16. 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 | 0, 0.5, 1, 2 hours post-dose at Week 0 and Week 16 | The change from Baseline in AUC0-2h for Postprandial Plasma Glucose collected at Week 16. 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 0 and Week 16 | The change from Baseline in 2-hour Postprandial Plasma Glucose collected at Week 16. 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 (Teneligliptin) + Insulin Placebo for 16 weeks (double-blind period) followed by teneligliptin (20 mg once daily, titrated to 40 mg if no adequate efficacy is obtained ) for an additional 36 weeks (open-label period) in combination with insulin. | 71 |
| Teneli (Teneligliptin) /Teneli + Insulin Teneligliptin (20 mg once daily) for 16 weeks (double-blind period) followed by teneligliptin (20 mg once daily, titrated to 40 mg if no adequate efficacy is obtained ) for an additional 36 weeks (open-label period) in combination with insulin. | 77 |
| Total | 148 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1：Double-blind Period | Adverse Event | 3 | 0 |
| Period 1：Double-blind Period | Lack of Efficacy | 2 | 1 |
| Period 1：Double-blind Period | Physician Decision | 1 | 0 |
| Period 1：Double-blind Period | Protocol Violation | 0 | 1 |
| Period 1：Double-blind Period | stopping criteria | 1 | 0 |
| Period 1：Double-blind Period | Withdrawal by Subject | 1 | 0 |
| Period 2：Open-label Period | Adverse Event | 1 | 0 |
| Period 2：Open-label Period | Lack of Efficacy | 2 | 4 |
| Period 2：Open-label Period | Physician Decision | 1 | 0 |
| Period 2：Open-label Period | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo/Teneli (Teneligliptin) + Insulin | Teneli (Teneligliptin) /Teneli + Insulin | Total |
|---|---|---|---|
| Age, Customized <65 years | 49 Participants | 46 Participants | 95 Participants |
| Age, Customized >=65 years | 22 Participants | 31 Participants | 53 Participants |
| Sex: Female, Male Female | 18 Participants | 18 Participants | 36 Participants |
| Sex: Female, Male Male | 53 Participants | 59 Participants | 112 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 | 18 / 71 | 14 / 77 | 25 / 63 | 45 / 77 |
| serious Total, serious adverse events | 2 / 71 | 1 / 77 | 5 / 63 | 5 / 77 |
Outcome results
Primary
Change From Baseline in HbA1c
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 16. 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 16
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 post baseline double-blind observed value was carried forward and used for Week 16 where data was missing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Teneli (Teneligliptin) + Insulin | Change From Baseline in HbA1c | -0.07 percentage of HbA1c | Standard Error 0.08 |
| Teneli (Teneligliptin) /Teneli + Insulin | Change From Baseline in HbA1c | -0.87 percentage of HbA1c | Standard Error 0.08 |
Secondary
Change From Baseline in 2-hour Postprandial Plasma Glucose
The change from Baseline in 2-hour Postprandial Plasma Glucose collected at Week 16. 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 16
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 (Teneligliptin) + Insulin | Change From Baseline in 2-hour Postprandial Plasma Glucose | 3.0 mg/dL | Standard Error 7.6 |
| Teneli (Teneligliptin) /Teneli + Insulin | Change From Baseline in 2-hour Postprandial Plasma Glucose | -42.9 mg/dL | Standard Error 7 |
Secondary
Change From Baseline in Fasting Plasma Glucose
The change from Baseline in Fasting Plasma Glucose collected at Week 16. 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 16
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 post baseline double-blind observed value was carried forward and used for Week 16 where data was missing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Teneli (Teneligliptin) + Insulin | Change From Baseline in Fasting Plasma Glucose | 8.0 mg/dL | Standard Error 4.6 |
| Teneli (Teneligliptin) /Teneli + Insulin | Change From Baseline in Fasting Plasma Glucose | -5.4 mg/dL | Standard Error 4.4 |
Secondary
Change From Baseline in the Areas Under the Curve From 0 to 2 h (AUC0-2h) for Postprandial Plasma Glucose
The change from Baseline in AUC0-2h for Postprandial Plasma Glucose collected at Week 16. 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 16
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 (Teneligliptin) + Insulin | Change From Baseline in the Areas Under the Curve From 0 to 2 h (AUC0-2h) for Postprandial Plasma Glucose | 9.827 mg*hr/dL | Standard Error 11.437 |
| Teneli (Teneligliptin) /Teneli + Insulin | Change From Baseline in the Areas Under the Curve From 0 to 2 h (AUC0-2h) for Postprandial Plasma Glucose | -54.035 mg*hr/dL | Standard Error 10.552 |