Type 2 Diabetes Mellitus (T2DM)
Conditions
Keywords
Diabetes Mellitus (DM) ,, diabetes,, noninsulin-dependent diabetes mellitus (NIDDM),, adult-onset diabetes,, high blood sugar,, T2DM
Brief summary
The purpose of this study was to assess the efficacy and safety of vildagliptin 50 mg bid add-on therapy to improve overall glycemic control in patients with T2DM inadequately controlled by insulin, with or without concomitant metformin treatment. It was agreed with PMDA to conduct a postmarketing clinical trial to further collect the efficacy and safety data of vildagliptin especially in Japanese patients when it iwas used on top of insulin.
Interventions
Corresponds to vildagliptin (LAF237) 50 mg tablets twice daily
DRUGPlacebo
Matching placebo of vildagliptin 50 mg twice daily
DRUGInsulin
Patients continued their prescribed insulin dose. The dose of insulin remained within a 10% increase of the baseline dose throughout the trial (with no change in frequency or insulin type) unless dose adjustments were required for safety reasons. The insulin dose was allowed to be decreased for safety reasons at anytime without specific dose limits at the Investigator's discretion.
DRUGMetformin
Patients continued their prescribed metformin dose, if applicable.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of T2DM by standard criteria. * HbA1c ≥ 7.0 to ≤ 10% at Visit 1. * Age: ≥ 20 to \< 75 years old at Visit 1. * BMI ≥ 20 to ≤ 35 kg/m2 at Visit 1.
Exclusion criteria
* FPG ≥ 270 mg/dL (≥15 mmol/L) at Visit 1. * Type 1 diabetes, monogenic diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes. * Significant heart diseases * Hepatic disorder Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 12 Weeks Between Treatment Groups | Baseline, week 12 | HbA1c was performed on a blood sample obtained and measured by high performance liquid chromatography performed at a central laboratory. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Meeting Responder Rates in HbA1c | Baseline, week 12 | Responder rate was analyzed in categories: Criterion 1- Endpoint HbA1c ≤ 6.5%, Criterion 2- Endpoint HbA1c \< 7% , Criterion 3- Endpoint HbA1c \< 7% in patients with baseline HbA1c ≤ 8%, Criterion 4- HbA1c reduction from baseline at endpoint ≥ 1%, Criterion 5- HbA1c reduction from baseline at endpoint ≥ 0.5%. The number of patients analyzed for Criterion 1 and 2 include only patients with baseline HbA1c ≥ 7% (\> 6.5%) and endpoint HbA1c measurement. The number of patients analyzed for Criterion 3 includes only patients with 7% ≤ baseline HbA1c ≤ 8% and endpoint HbA1c measurement. The number of patients analyzed for Criterion 4 and 5 include patients with both baseline and endpoint HbA1c measurements. |
| Change From Baseline in Fasting Plasma Glucose (FPG) at 12 Weeks | Baseline, week 12 | FPG was performed on a blood sample obtained and analyzed at a central laboratory. |
| Number of Participants With Incidence of Hypoglycemia and Severe Hypoglycemia | 12 weeks | Hypoglycemic events are defined as a) symptoms suggestive of hypoglycemia, where the patient is able to initiate self-treatment and plasma glucose measurement is \< 56 mg/dL (grade 1), b) symptoms suggestive of hypoglycemia, where the patient is unable to initiate self-treatment and plasma glucose measurement is \< 56 mg/dL (grade 2), c) symptoms suggestive of hypoglycemia, where the patient is unable to initiate self-treatment and no plasma glucose measurement is available (suspected grade 2) |
| Number of Participants With Adverse Events, Serious Adverse Events and Death | 12 weeks | The occurrence of adverse events was sought by non-directive questioning of the patient at each visit. Adverse events are defined as appearance or worsening of any undesirable symptom, vital sign, or medical conditions. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vildagliptin (LAF237) Patients received vildagliptin (LAF237) 50 mg tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study | 78 |
| Placebo In this arm, patients received vildagliptin 50 mg matching placebo tablets twice daily for 12 weeks. Patients continued on a stable dose of long-acting or intermediate-acting or pre-mixed insulin, and metformin if applicable, throughout the study | 78 |
| Total | 156 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Patient withdrew consent | 0 | 1 |
| Overall Study | Unsatisfactory therapeutic effect | 0 | 1 |
Baseline characteristics
| Characteristic | Vildagliptin (LAF237) | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 58.5 Years STANDARD_DEVIATION 9.57 | 60.1 Years STANDARD_DEVIATION 9.11 | 59.3 Years STANDARD_DEVIATION 9.34 |
| Sex: Female, Male Female | 23 Participants | 22 Participants | 45 Participants |
| Sex: Female, Male Male | 55 Participants | 56 Participants | 111 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 78 | 21 / 78 |
| serious Total, serious adverse events | 2 / 78 | 1 / 78 |
Outcome results
Primary
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 12 Weeks Between Treatment Groups
HbA1c was performed on a blood sample obtained and measured by high performance liquid chromatography performed at a central laboratory.
Time frame: Baseline, week 12
Population: The full analysis set consisted of all randomized patients who received at least one dose of study medication and had at least one post-baseline assessment of efficacy parameter measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vildagliptin (LAF237) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 12 Weeks Between Treatment Groups | -1.01 percentage of glycosylated haemoglobin | Standard Error 0.06 |
| Placebo | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 12 Weeks Between Treatment Groups | -0.11 percentage of glycosylated haemoglobin | Standard Error 0.06 |
Comparison: H0: δ vildagliptin 50 mg bid = δ placebo versus H1: δ Vildagliptin 50 mg bid \< δ placebo,p-value: <0.00195% CI: [-1.08, -0.73]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at 12 Weeks
FPG was performed on a blood sample obtained and analyzed at a central laboratory.
Time frame: Baseline, week 12
Population: The full analysis set consisted of all randomized patients who received at least one dose of study medication and had at least one post-baseline assessment of efficacy parameter measurement. Number of patients with observations at both baseline and endpoint are analyzed in this endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vildagliptin (LAF237) | Change From Baseline in Fasting Plasma Glucose (FPG) at 12 Weeks | -21.87 mg/dL | Standard Error 4.05 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at 12 Weeks | -0.30 mg/dL | Standard Error 4.04 |
Secondary
Number of Participants With Adverse Events, Serious Adverse Events and Death
The occurrence of adverse events was sought by non-directive questioning of the patient at each visit. Adverse events are defined as appearance or worsening of any undesirable symptom, vital sign, or medical conditions. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
Time frame: 12 weeks
Population: The safety set consisted of all patients who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vildagliptin (LAF237) | Number of Participants With Adverse Events, Serious Adverse Events and Death | Any adverse events | 36 Participants |
| Vildagliptin (LAF237) | Number of Participants With Adverse Events, Serious Adverse Events and Death | Serious adverse events | 2 Participants |
| Vildagliptin (LAF237) | Number of Participants With Adverse Events, Serious Adverse Events and Death | Death | 0 Participants |
| Placebo | Number of Participants With Adverse Events, Serious Adverse Events and Death | Any adverse events | 34 Participants |
| Placebo | Number of Participants With Adverse Events, Serious Adverse Events and Death | Serious adverse events | 1 Participants |
| Placebo | Number of Participants With Adverse Events, Serious Adverse Events and Death | Death | 0 Participants |
Secondary
Number of Participants With Incidence of Hypoglycemia and Severe Hypoglycemia
Hypoglycemic events are defined as a) symptoms suggestive of hypoglycemia, where the patient is able to initiate self-treatment and plasma glucose measurement is \< 56 mg/dL (grade 1), b) symptoms suggestive of hypoglycemia, where the patient is unable to initiate self-treatment and plasma glucose measurement is \< 56 mg/dL (grade 2), c) symptoms suggestive of hypoglycemia, where the patient is unable to initiate self-treatment and no plasma glucose measurement is available (suspected grade 2)
Time frame: 12 weeks
Population: The safety set consisted of all patients who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vildagliptin (LAF237) | Number of Participants With Incidence of Hypoglycemia and Severe Hypoglycemia | at least one hypoglycemic event | 5 Participants |
| Vildagliptin (LAF237) | Number of Participants With Incidence of Hypoglycemia and Severe Hypoglycemia | grade 2 hypoglycemic events | 0 Participants |
| Vildagliptin (LAF237) | Number of Participants With Incidence of Hypoglycemia and Severe Hypoglycemia | suspected grade 2 hypoglycemic events | 0 Participants |
| Placebo | Number of Participants With Incidence of Hypoglycemia and Severe Hypoglycemia | at least one hypoglycemic event | 1 Participants |
| Placebo | Number of Participants With Incidence of Hypoglycemia and Severe Hypoglycemia | grade 2 hypoglycemic events | 0 Participants |
| Placebo | Number of Participants With Incidence of Hypoglycemia and Severe Hypoglycemia | suspected grade 2 hypoglycemic events | 0 Participants |
Secondary
Percentage of Patients Meeting Responder Rates in HbA1c
Responder rate was analyzed in categories: Criterion 1- Endpoint HbA1c ≤ 6.5%, Criterion 2- Endpoint HbA1c \< 7% , Criterion 3- Endpoint HbA1c \< 7% in patients with baseline HbA1c ≤ 8%, Criterion 4- HbA1c reduction from baseline at endpoint ≥ 1%, Criterion 5- HbA1c reduction from baseline at endpoint ≥ 0.5%. The number of patients analyzed for Criterion 1 and 2 include only patients with baseline HbA1c ≥ 7% (\> 6.5%) and endpoint HbA1c measurement. The number of patients analyzed for Criterion 3 includes only patients with 7% ≤ baseline HbA1c ≤ 8% and endpoint HbA1c measurement. The number of patients analyzed for Criterion 4 and 5 include patients with both baseline and endpoint HbA1c measurements.
Time frame: Baseline, week 12
Population: The full analysis set consisted of all randomized patients who received at least one dose of study medication and had at least one post-baseline assessment of efficacy parameter measurement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vildagliptin (LAF237) | Percentage of Patients Meeting Responder Rates in HbA1c | At least one criterion met (n = 78, 78) | 67 percentage of patients |
| Vildagliptin (LAF237) | Percentage of Patients Meeting Responder Rates in HbA1c | Criterion 1 (n= 77, 78) | 23 percentage of patients |
| Vildagliptin (LAF237) | Percentage of Patients Meeting Responder Rates in HbA1c | Criterion 2 (n= 76, 77) | 38 percentage of patients |
| Vildagliptin (LAF237) | Percentage of Patients Meeting Responder Rates in HbA1c | Criterion 3 (n= 42, 37) | 33 percentage of patients |
| Vildagliptin (LAF237) | Percentage of Patients Meeting Responder Rates in HbA1c | Criterion 4 (n=78, 78) | 38 percentage of patients |
| Vildagliptin (LAF237) | Percentage of Patients Meeting Responder Rates in HbA1c | Criterion 5 (n= 78, 78) | 62 percentage of patients |
| Placebo | Percentage of Patients Meeting Responder Rates in HbA1c | Criterion 4 (n=78, 78) | 5 percentage of patients |
| Placebo | Percentage of Patients Meeting Responder Rates in HbA1c | At least one criterion met (n = 78, 78) | 21 percentage of patients |
| Placebo | Percentage of Patients Meeting Responder Rates in HbA1c | Criterion 3 (n= 42, 37) | 3 percentage of patients |
| Placebo | Percentage of Patients Meeting Responder Rates in HbA1c | Criterion 1 (n= 77, 78) | 2 percentage of patients |
| Placebo | Percentage of Patients Meeting Responder Rates in HbA1c | Criterion 5 (n= 78, 78) | 20 percentage of patients |
| Placebo | Percentage of Patients Meeting Responder Rates in HbA1c | Criterion 2 (n= 76, 77) | 3 percentage of patients |