Type-2 Diabetes Mellitus
Conditions
Keywords
type-2 diabetes mellitus, inadequately controlled Metformin
Brief summary
The purpose of this study was to observe change of HbA1c over time from baseline to month 12. The ultimate goal of this study was to provide a local reference value to the physicians & patients in the future when they consider initiating Vildagliptin and taking balance between efficacy, compliance, risk factors, convenience and medication cost.
Interventions
DRUGLAF237 (vildagliptin)
Vildagliptin 50mg capsule
DRUGMetformin
Metformin maximum tolerance dose
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or Female in age ≥18 at Visit 1 2. Type 2 diabetes mellitus (T2DM) patients on their maximum tolerated dose of Metformin for more than 3 months 3. HbA1c (glycosylated hemoglobin) at Visit 1 greater than 7.0% 4. With nearest documented record of HbA1c before Visit 1 greater than 7.0% after patient reached his/her maximum tolerated dose of Metformin Key
Exclusion criteria
1. Patients with hepatic impairment, including patients with a pre-treatment alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5 X the upper limit of normal at Visit 1 2. Patients with moderate or severe renal impairment or end-stage-renal-disease (ESRD) on haemodialysis at the time of enrolment 3. Patients with hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption 4. Pregnant women or breastfeeding women at the time of enrolment 5. Use of insulin or other oral anti-diabetic drug (OAD) apart from Metformin in the past for T2DM treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Month 12 | Baseline, Month 12 (weeK 52) | HbA1c is an integrated measure of average glucose concentration in plasma in the last 2-3 months. Blood samples were collected to analyze HbA1c |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis) | Baseline, Month 3, 6, 9 and 12 | HbA1c is an integrated measure of average glucose concentration in plasma in the last 2-3 months. Blood samples were collected to analyze HbA1c. Mixed Model of Repeated Measures (MMRM) was used to analyze this outcome. For the MMRM analysis, the model includes terms for treatment, period, treatment-by-period interaction and baseline value, and further adjusted by age, pre-existing hypertension and microvascular and macrovascular complications for diabetes mellitus. The variables selected for baseline adjustment were based on the lowest AIC. |
| Change in Fasting Plasma Glucose (FPG) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis) | Baseline, Month 3, 6, 9 and 12 | Blood samples were collected to analyze fasting plasma glucose. Mixed Model of Repeated Measures (MMRM) was used to analyze this outcome. For the MMRM analysis, the model included terms for treatment, period, treatment-by-period interaction and baseline value, and further adjusted by pre-existing hypertension. The variable selected for baseline adjustment was based on the lowest AIC. |
| Percentage of Patients Achieving Good Glycemic Control | Month 3, 6, 9, 12 | Blood samples were collected to analyze HbA1c. Good glycemic control is defined as patient achieving Hb1Ac \< 7.0%. Percentage of patients who achieved HbA1c less than 7.0% at month 3, 6, 9 and 12 were reported for this endpoint. |
| Percentage of Overall Drug Compliance in 12 Months | Month 12 | The overall drug compliance (%) = (Observed Consumption / Expected Consumption) x 100% Where (Observed Consumption / Expected Consumption) = \[1- (Number of missing tablets from all visits/(sum of Allocated Daily Dosage (in tablets) from all visits × No. of Days between the Date Dispensed and the Date Returned))\] |
| Number of Patients With Adverse Events, Serious Adverse Events and Death as an Assessment of Overall Safety and Tolerability | Month 12 | This analysis reported percentage patients with adverse events and patient discontinued from the study due to adverse events. Aslo, percentage of patients with serious adverse events and death was reported. |
Countries
Hong Kong
Participant flow
Pre-assignment details
There was 117 patients randomized and received either Vildagliptin 50mg QD or 50 mg BID.
Participants by arm
| Arm | Count |
|---|---|
| LAF237 (Vildagliptin) 50mg Once Daily (QD) Vildagliptin 50mg QD plus stabilized or maximum tolerated dose of Metformin | 56 |
| LAF237 (Vildagliptin) 50mg Twice Daily (BID) Vildagliptin 50mg BID plus stabilized or maximum tolerated dose of Metformin | 61 |
| Total | 117 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 4 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | LAF237 (Vildagliptin) 50mg Once Daily (QD) | LAF237 (Vildagliptin) 50mg Twice Daily (BID) | Total |
|---|---|---|---|
| Age, Continuous | 58 Years STANDARD_DEVIATION 10.3 | 59 Years STANDARD_DEVIATION 10 | 58 Years STANDARD_DEVIATION 10.1 |
| Sex: Female, Male Female | 26 Participants | 31 Participants | 57 Participants |
| Sex: Female, Male Male | 30 Participants | 30 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 56 | 7 / 61 |
| serious Total, serious adverse events | 2 / 56 | 2 / 61 |
Outcome results
Primary
Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Month 12
HbA1c is an integrated measure of average glucose concentration in plasma in the last 2-3 months. Blood samples were collected to analyze HbA1c
Time frame: Baseline, Month 12 (weeK 52)
Population: Intent to treat (ITT) analysis set included all randomized patients who received at least one dose of study medication. Patients with both baseline and 12 month data were included in this analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LAF237 (Vildagliptin) 50mg Once Daily (QD) | Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Month 12 | -0.8 percentage of Glycosylated Hemoglobin | Standard Deviation 1.01 |
| LAF237 (Vildagliptin) 50mg Twice Daily (BID) | Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Month 12 | -1.0 percentage of Glycosylated Hemoglobin | Standard Deviation 1.24 |
Secondary
Change in Fasting Plasma Glucose (FPG) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis)
Blood samples were collected to analyze fasting plasma glucose. Mixed Model of Repeated Measures (MMRM) was used to analyze this outcome. For the MMRM analysis, the model included terms for treatment, period, treatment-by-period interaction and baseline value, and further adjusted by pre-existing hypertension. The variable selected for baseline adjustment was based on the lowest AIC.
Time frame: Baseline, Month 3, 6, 9 and 12
Population: Intent to treat (ITT) analysis set included all randomized patients who received at least one dose of study medication.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LAF237 (Vildagliptin) 50mg Once Daily (QD) | Change in Fasting Plasma Glucose (FPG) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis) | 3 month from baseline | -0.9 mmol/L | Standard Error 0.18 |
| LAF237 (Vildagliptin) 50mg Once Daily (QD) | Change in Fasting Plasma Glucose (FPG) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis) | 6 month from baseline | -1.2 mmol/L | Standard Error 0.18 |
| LAF237 (Vildagliptin) 50mg Once Daily (QD) | Change in Fasting Plasma Glucose (FPG) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis) | 9 month from baseline | -1.1 mmol/L | Standard Error 0.17 |
| LAF237 (Vildagliptin) 50mg Once Daily (QD) | Change in Fasting Plasma Glucose (FPG) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis) | 12 month from baseline | -0.9 mmol/L | Standard Error 0.2 |
| LAF237 (Vildagliptin) 50mg Twice Daily (BID) | Change in Fasting Plasma Glucose (FPG) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis) | 12 month from baseline | -0.8 mmol/L | Standard Error 0.2 |
| LAF237 (Vildagliptin) 50mg Twice Daily (BID) | Change in Fasting Plasma Glucose (FPG) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis) | 3 month from baseline | -1.3 mmol/L | Standard Error 0.16 |
| LAF237 (Vildagliptin) 50mg Twice Daily (BID) | Change in Fasting Plasma Glucose (FPG) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis) | 9 month from baseline | -1.0 mmol/L | Standard Error 0.16 |
| LAF237 (Vildagliptin) 50mg Twice Daily (BID) | Change in Fasting Plasma Glucose (FPG) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis) | 6 month from baseline | -0.9 mmol/L | Standard Error 0.17 |
Secondary
Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis)
HbA1c is an integrated measure of average glucose concentration in plasma in the last 2-3 months. Blood samples were collected to analyze HbA1c. Mixed Model of Repeated Measures (MMRM) was used to analyze this outcome. For the MMRM analysis, the model includes terms for treatment, period, treatment-by-period interaction and baseline value, and further adjusted by age, pre-existing hypertension and microvascular and macrovascular complications for diabetes mellitus. The variables selected for baseline adjustment were based on the lowest AIC.
Time frame: Baseline, Month 3, 6, 9 and 12
Population: Intent to treat (ITT) analysis set included all randomized patients who received at least one dose of study medication. .
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LAF237 (Vildagliptin) 50mg Once Daily (QD) | Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis) | 3 month from baseline | -0.6 percentage of Glycosylated Hemoglobin | Standard Error 0.11 |
| LAF237 (Vildagliptin) 50mg Once Daily (QD) | Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis) | 6 month from baseline | -0.7 percentage of Glycosylated Hemoglobin | Standard Error 0.13 |
| LAF237 (Vildagliptin) 50mg Once Daily (QD) | Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis) | 9 month from baseline | -0.7 percentage of Glycosylated Hemoglobin | Standard Error 0.13 |
| LAF237 (Vildagliptin) 50mg Once Daily (QD) | Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis) | 12 month from baseline | -0.6 percentage of Glycosylated Hemoglobin | Standard Error 0.15 |
| LAF237 (Vildagliptin) 50mg Twice Daily (BID) | Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis) | 12 month from baseline | -0.6 percentage of Glycosylated Hemoglobin | Standard Error 0.15 |
| LAF237 (Vildagliptin) 50mg Twice Daily (BID) | Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis) | 3 month from baseline | -0.9 percentage of Glycosylated Hemoglobin | Standard Error 0.1 |
| LAF237 (Vildagliptin) 50mg Twice Daily (BID) | Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis) | 9 month from baseline | -0.7 percentage of Glycosylated Hemoglobin | Standard Error 0.13 |
| LAF237 (Vildagliptin) 50mg Twice Daily (BID) | Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Month 3, 6, 9 and 12 (Based on MMRM Analysis) | 6 month from baseline | -0.9 percentage of Glycosylated Hemoglobin | Standard Error 0.12 |
Secondary
Number of Patients With Adverse Events, Serious Adverse Events and Death as an Assessment of Overall Safety and Tolerability
This analysis reported percentage patients with adverse events and patient discontinued from the study due to adverse events. Aslo, percentage of patients with serious adverse events and death was reported.
Time frame: Month 12
Population: Intent to treat (ITT) analysis set included all randomized patients who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LAF237 (Vildagliptin) 50mg Once Daily (QD) | Number of Patients With Adverse Events, Serious Adverse Events and Death as an Assessment of Overall Safety and Tolerability | Death | 0 Patients |
| LAF237 (Vildagliptin) 50mg Once Daily (QD) | Number of Patients With Adverse Events, Serious Adverse Events and Death as an Assessment of Overall Safety and Tolerability | Serious adverse events | 2 Patients |
| LAF237 (Vildagliptin) 50mg Once Daily (QD) | Number of Patients With Adverse Events, Serious Adverse Events and Death as an Assessment of Overall Safety and Tolerability | Patients discontinued due to any AE/SAE | 4 Patients |
| LAF237 (Vildagliptin) 50mg Once Daily (QD) | Number of Patients With Adverse Events, Serious Adverse Events and Death as an Assessment of Overall Safety and Tolerability | Any adverse events | 15 Patients |
| LAF237 (Vildagliptin) 50mg Twice Daily (BID) | Number of Patients With Adverse Events, Serious Adverse Events and Death as an Assessment of Overall Safety and Tolerability | Patients discontinued due to any AE/SAE | 4 Patients |
| LAF237 (Vildagliptin) 50mg Twice Daily (BID) | Number of Patients With Adverse Events, Serious Adverse Events and Death as an Assessment of Overall Safety and Tolerability | Serious adverse events | 2 Patients |
| LAF237 (Vildagliptin) 50mg Twice Daily (BID) | Number of Patients With Adverse Events, Serious Adverse Events and Death as an Assessment of Overall Safety and Tolerability | Death | 0 Patients |
| LAF237 (Vildagliptin) 50mg Twice Daily (BID) | Number of Patients With Adverse Events, Serious Adverse Events and Death as an Assessment of Overall Safety and Tolerability | Any adverse events | 14 Patients |
Secondary
Percentage of Overall Drug Compliance in 12 Months
The overall drug compliance (%) = (Observed Consumption / Expected Consumption) x 100% Where (Observed Consumption / Expected Consumption) = \[1- (Number of missing tablets from all visits/(sum of Allocated Daily Dosage (in tablets) from all visits × No. of Days between the Date Dispensed and the Date Returned))\]
Time frame: Month 12
Population: Intent to treat (ITT) analysis set included all randomized patients who received at least one dose of study medication. Patients who had reported dosing compliance were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LAF237 (Vildagliptin) 50mg Once Daily (QD) | Percentage of Overall Drug Compliance in 12 Months | 96.90 Percentage of overall drug compliance | Standard Deviation 5.682 |
| LAF237 (Vildagliptin) 50mg Twice Daily (BID) | Percentage of Overall Drug Compliance in 12 Months | 97.48 Percentage of overall drug compliance | Standard Deviation 6.277 |
Secondary
Percentage of Patients Achieving Good Glycemic Control
Blood samples were collected to analyze HbA1c. Good glycemic control is defined as patient achieving Hb1Ac \< 7.0%. Percentage of patients who achieved HbA1c less than 7.0% at month 3, 6, 9 and 12 were reported for this endpoint.
Time frame: Month 3, 6, 9, 12
Population: Intent to treat (ITT) analysis set included all randomized patients who received at least one dose of study medication. 'n' indicates patients with HbA1c data in that time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LAF237 (Vildagliptin) 50mg Once Daily (QD) | Percentage of Patients Achieving Good Glycemic Control | At Month 3 | 33.3 Percentage of patients |
| LAF237 (Vildagliptin) 50mg Once Daily (QD) | Percentage of Patients Achieving Good Glycemic Control | At Month 6 | 39.2 Percentage of patients |
| LAF237 (Vildagliptin) 50mg Once Daily (QD) | Percentage of Patients Achieving Good Glycemic Control | At Month 9 | 45.1 Percentage of patients |
| LAF237 (Vildagliptin) 50mg Once Daily (QD) | Percentage of Patients Achieving Good Glycemic Control | At Month 12 | 49.0 Percentage of patients |
| LAF237 (Vildagliptin) 50mg Twice Daily (BID) | Percentage of Patients Achieving Good Glycemic Control | At Month 12 | 40.0 Percentage of patients |
| LAF237 (Vildagliptin) 50mg Twice Daily (BID) | Percentage of Patients Achieving Good Glycemic Control | At Month 3 | 47.5 Percentage of patients |
| LAF237 (Vildagliptin) 50mg Twice Daily (BID) | Percentage of Patients Achieving Good Glycemic Control | At Month 9 | 47.4 Percentage of patients |
| LAF237 (Vildagliptin) 50mg Twice Daily (BID) | Percentage of Patients Achieving Good Glycemic Control | At Month 6 | 45.6 Percentage of patients |