Trial Outcomes & Findings for Early add-on Vildagliptin in Patients With Type 2 Diabetes Inadequately Controlled by Metformin (NCT NCT01766778)
NCT ID: NCT01766778
Last Updated: 2017-05-15
Results Overview
HbA1c is an integrated measure of average glucose concentration in plasma in the last 2-3 months. Blood samples were collected to analyze HbA1c
COMPLETED
PHASE4
117 participants
Baseline, Month 12 (weeK 52)
2017-05-15
Participant Flow
There was 117 patients randomized and received either Vildagliptin 50mg QD or 50 mg BID.
Participant milestones
| Measure |
LAF237 (Vildagliptin) 50mg Once Daily (QD)
Vildagliptin 50mg QD plus stabilized or maximum tolerated dose of Metformin
|
LAF237 (Vildagliptin) 50mg Twice Daily (BID)
Vildagliptin 50mg BID plus stabilized or maximum tolerated dose of Metformin
|
|---|---|---|
|
Overall Study
STARTED
|
56
|
61
|
|
Overall Study
COMPLETED
|
51
|
57
|
|
Overall Study
NOT COMPLETED
|
5
|
4
|
Reasons for withdrawal
| Measure |
LAF237 (Vildagliptin) 50mg Once Daily (QD)
Vildagliptin 50mg QD plus stabilized or maximum tolerated dose of Metformin
|
LAF237 (Vildagliptin) 50mg Twice Daily (BID)
Vildagliptin 50mg BID plus stabilized or maximum tolerated dose of Metformin
|
|---|---|---|
|
Overall Study
Adverse Event
|
4
|
4
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Early add-on Vildagliptin in Patients With Type 2 Diabetes Inadequately Controlled by Metformin
Baseline characteristics by cohort
| Measure |
LAF237 (Vildagliptin) 50mg Once Daily (QD)
n=56 Participants
Vildagliptin 50mg QD plus stabilized or maximum tolerated dose of Metformin
|
LAF237 (Vildagliptin) 50mg Twice Daily (BID)
n=61 Participants
Vildagliptin 50mg BID plus stabilized or maximum tolerated dose of Metformin
|
Total
n=117 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
58 Years
STANDARD_DEVIATION 10.3 • n=5 Participants
|
59 Years
STANDARD_DEVIATION 10.0 • n=7 Participants
|
58 Years
STANDARD_DEVIATION 10.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
26 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
57 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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
HbA1c is an integrated measure of average glucose concentration in plasma in the last 2-3 months. Blood samples were collected to analyze HbA1c
Outcome measures
| Measure |
LAF237 (Vildagliptin) 50mg Once Daily (QD)
n=49 Participants
Vildagliptin 50mg QD plus stabilized or maximum tolerated dose of Metformin
|
LAF237 (Vildagliptin) 50mg Twice Daily (BID)
n=50 Participants
Vildagliptin 50mg BID plus stabilized or maximum tolerated dose of Metformin
|
|---|---|---|
|
Change of Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Month 12
|
-0.8 percentage of Glycosylated Hemoglobin
Standard Deviation 1.01
|
-1.0 percentage of Glycosylated Hemoglobin
Standard Deviation 1.24
|
SECONDARY outcome
Timeframe: Baseline, Month 3, 6, 9 and 12Population: Intent to treat (ITT) analysis set included all randomized patients who received at least one dose of study medication. .
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.
Outcome measures
| Measure |
LAF237 (Vildagliptin) 50mg Once Daily (QD)
n=56 Participants
Vildagliptin 50mg QD plus stabilized or maximum tolerated dose of Metformin
|
LAF237 (Vildagliptin) 50mg Twice Daily (BID)
n=61 Participants
Vildagliptin 50mg BID plus stabilized or maximum tolerated dose of Metformin
|
|---|---|---|
|
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
|
-0.9 percentage of Glycosylated Hemoglobin
Standard Error 0.10
|
|
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
|
-0.9 percentage of Glycosylated Hemoglobin
Standard Error 0.12
|
|
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
|
-0.7 percentage of Glycosylated Hemoglobin
Standard Error 0.13
|
|
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
|
-0.6 percentage of Glycosylated Hemoglobin
Standard Error 0.15
|
SECONDARY outcome
Timeframe: Baseline, Month 3, 6, 9 and 12Population: Intent to treat (ITT) analysis set included all randomized patients who received at least one dose of study medication.
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.
Outcome measures
| Measure |
LAF237 (Vildagliptin) 50mg Once Daily (QD)
n=56 Participants
Vildagliptin 50mg QD plus stabilized or maximum tolerated dose of Metformin
|
LAF237 (Vildagliptin) 50mg Twice Daily (BID)
n=61 Participants
Vildagliptin 50mg BID plus stabilized or maximum tolerated dose of Metformin
|
|---|---|---|
|
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
|
-1.3 mmol/L
Standard Error 0.16
|
|
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
|
-0.9 mmol/L
Standard Error 0.17
|
|
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
|
-1.0 mmol/L
Standard Error 0.16
|
|
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 0.20
|
-0.8 mmol/L
Standard Error 0.20
|
SECONDARY outcome
Timeframe: Month 3, 6, 9, 12Population: 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.
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.
Outcome measures
| Measure |
LAF237 (Vildagliptin) 50mg Once Daily (QD)
n=56 Participants
Vildagliptin 50mg QD plus stabilized or maximum tolerated dose of Metformin
|
LAF237 (Vildagliptin) 50mg Twice Daily (BID)
n=61 Participants
Vildagliptin 50mg BID plus stabilized or maximum tolerated dose of Metformin
|
|---|---|---|
|
Percentage of Patients Achieving Good Glycemic Control
At Month 12
|
49.0 Percentage of patients
|
40.0 Percentage of patients
|
|
Percentage of Patients Achieving Good Glycemic Control
At Month 3
|
33.3 Percentage of patients
|
47.5 Percentage of patients
|
|
Percentage of Patients Achieving Good Glycemic Control
At Month 6
|
39.2 Percentage of patients
|
45.6 Percentage of patients
|
|
Percentage of Patients Achieving Good Glycemic Control
At Month 9
|
45.1 Percentage of patients
|
47.4 Percentage of patients
|
SECONDARY outcome
Timeframe: Month 12Population: 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.
The overall drug compliance (%) = (Observed Consumption / Expected Consumption) x 100% Where (Observed Consumption / Expected Consumption) = \[1- (Number of missing tablets from all visits/(sum of Allocated Daily Dosage (in tablets) from all visits × No. of Days between the Date Dispensed and the Date Returned))\]
Outcome measures
| Measure |
LAF237 (Vildagliptin) 50mg Once Daily (QD)
n=21 Participants
Vildagliptin 50mg QD plus stabilized or maximum tolerated dose of Metformin
|
LAF237 (Vildagliptin) 50mg Twice Daily (BID)
n=21 Participants
Vildagliptin 50mg BID plus stabilized or maximum tolerated dose of Metformin
|
|---|---|---|
|
Percentage of Overall Drug Compliance in 12 Months
|
96.90 Percentage of overall drug compliance
Standard Deviation 5.682
|
97.48 Percentage of overall drug compliance
Standard Deviation 6.277
|
SECONDARY outcome
Timeframe: Month 12Population: Intent to treat (ITT) analysis set included all randomized patients who received at least one dose of study medication.
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.
Outcome measures
| Measure |
LAF237 (Vildagliptin) 50mg Once Daily (QD)
n=56 Participants
Vildagliptin 50mg QD plus stabilized or maximum tolerated dose of Metformin
|
LAF237 (Vildagliptin) 50mg Twice Daily (BID)
n=61 Participants
Vildagliptin 50mg BID plus stabilized or maximum tolerated dose of Metformin
|
|---|---|---|
|
Number of Patients With Adverse Events, Serious Adverse Events and Death as an Assessment of Overall Safety and Tolerability
Any adverse events
|
15 Patients
|
14 Patients
|
|
Number of Patients With Adverse Events, Serious Adverse Events and Death as an Assessment of Overall Safety and Tolerability
Serious adverse events
|
2 Patients
|
2 Patients
|
|
Number of Patients With Adverse Events, Serious Adverse Events and Death as an Assessment of Overall Safety and Tolerability
Death
|
0 Patients
|
0 Patients
|
|
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
|
4 Patients
|
Adverse Events
LAF237 (Vildagliptin) 50mg Once Daily (QD)
LAF237 (Vildagliptin) 50mg Twice Daily (BID)
Serious adverse events
| Measure |
LAF237 (Vildagliptin) 50mg Once Daily (QD)
n=56 participants at risk
Vildagliptin 50mg QD plus stabilized or maximum tolerated dose of Metformin
|
LAF237 (Vildagliptin) 50mg Twice Daily (BID)
n=61 participants at risk
Vildagliptin 50mg BID plus stabilized or maximum tolerated dose of Metformin
|
|---|---|---|
|
Gastrointestinal disorders
Duodenitis
|
1.8%
1/56
|
0.00%
0/61
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Leukemia
|
0.00%
0/56
|
1.6%
1/61
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/56
|
1.6%
1/61
|
|
Renal and urinary disorders
stone impairation over proximal urethra
|
1.8%
1/56
|
0.00%
0/61
|
Other adverse events
| Measure |
LAF237 (Vildagliptin) 50mg Once Daily (QD)
n=56 participants at risk
Vildagliptin 50mg QD plus stabilized or maximum tolerated dose of Metformin
|
LAF237 (Vildagliptin) 50mg Twice Daily (BID)
n=61 participants at risk
Vildagliptin 50mg BID plus stabilized or maximum tolerated dose of Metformin
|
|---|---|---|
|
Infections and infestations
Tinea
|
0.00%
0/56
|
3.3%
2/61
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
14.3%
8/56
|
3.3%
2/61
|
|
Investigations
Elevated liver function test
|
3.6%
2/56
|
3.3%
2/61
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
1.8%
1/56
|
3.3%
2/61
|
|
Metabolism and nutrition disorders
Hypokalemia
|
3.6%
2/56
|
0.00%
0/61
|
|
Nervous system disorders
Dizziness
|
3.6%
2/56
|
1.6%
1/61
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.6%
2/56
|
3.3%
2/61
|
|
Skin and subcutaneous tissue disorders
Eczema
|
3.6%
2/56
|
1.6%
1/61
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER