Trial Outcomes & Findings for Glycemic Excursions in Type 2 Diabetic Patients With Vildagliptin and Metformin Versus Vildagliptin and Glimepiride (NCT NCT02007278)
NCT ID: NCT02007278
Last Updated: 2017-07-11
Results Overview
Mean Amplitude of Glycemic Excursions (MAGE) , which determines the average blood glucose excursions either above or below a value of one standard deviation of the average value of glucose in a given day. MAGE is calculated from the data of continuous tissue glucose monitoring obtained during the measurement period. MAGE is calculated with the formula Σ λ / χ if λ\> ν (where λ = changes in blood glucose from peak to nadir, χ = number of valid observations, ν = 1 standard deviation of the mean glucose during a period of 24 hours) from the data of continuous monitoring of the tissue glucose, obtained during the period of measurement.
COMPLETED
PHASE4
40 participants
Week 12
2017-07-11
Participant Flow
A total of 9 research centers participated in the study, from which 76 patients were screened for inclusion and exclusion criteria, obtaining 40 patients eligible for randomization
Participant milestones
| Measure |
Vildagliptin and Metformin
Based on basal dose of metformin, administration of vildagliptin/metformin 50 mg/850 mg twice daily (bid) or 50 mg/1000 mg bid for 12 weeks
|
Glimepiride and Metformin
Protocol specified dosage and frequency of glimepiride + metformin for 12 weeks based on basal dose of metformin
|
|---|---|---|
|
Overall Study
STARTED
|
20
|
20
|
|
Overall Study
COMPLETED
|
18
|
17
|
|
Overall Study
NOT COMPLETED
|
2
|
3
|
Reasons for withdrawal
| Measure |
Vildagliptin and Metformin
Based on basal dose of metformin, administration of vildagliptin/metformin 50 mg/850 mg twice daily (bid) or 50 mg/1000 mg bid for 12 weeks
|
Glimepiride and Metformin
Protocol specified dosage and frequency of glimepiride + metformin for 12 weeks based on basal dose of metformin
|
|---|---|---|
|
Overall Study
Failure to comply with an eligibility
|
0
|
1
|
|
Overall Study
Ingestion of drugs not allowed in study
|
0
|
1
|
|
Overall Study
Incorrect medication administration
|
1
|
0
|
|
Overall Study
Mis-randomization
|
1
|
1
|
Baseline Characteristics
Glycemic Excursions in Type 2 Diabetic Patients With Vildagliptin and Metformin Versus Vildagliptin and Glimepiride
Baseline characteristics by cohort
| Measure |
Vildagliptin and Metformin
n=20 Participants
Based on basal dose of metformin, administration of vildagliptin/metformin 50 mg/850 mg twice daily (bid) or 50 mg/1000 mg bid for 12 weeks
|
Glimepiride and Metformin
n=20 Participants
Protocol specified dosage and frequency of glimepiride + metformin for 12 weeks based on basal dose of metformin
|
Total
n=40 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
56.74 Years
STANDARD_DEVIATION 10.58 • n=99 Participants
|
55.70 Years
STANDARD_DEVIATION 11.51 • n=107 Participants
|
56.25 Years
STANDARD_DEVIATION 10.92 • n=206 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
23 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
17 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Week 12Population: Analysis set includes all randomized patients excluding the ones who were prematurely withdrawn and the ones who have no data from visit 7 which required for comparison.
Mean Amplitude of Glycemic Excursions (MAGE) , which determines the average blood glucose excursions either above or below a value of one standard deviation of the average value of glucose in a given day. MAGE is calculated from the data of continuous tissue glucose monitoring obtained during the measurement period. MAGE is calculated with the formula Σ λ / χ if λ\> ν (where λ = changes in blood glucose from peak to nadir, χ = number of valid observations, ν = 1 standard deviation of the mean glucose during a period of 24 hours) from the data of continuous monitoring of the tissue glucose, obtained during the period of measurement.
Outcome measures
| Measure |
Vildagliptin and Metformin
n=16 Participants
Based on basal dose of metformin, administration of vildagliptin/metformin 50 mg/850 mg twice daily (bid) or 50 mg/1000 mg bid for 12 weeks
|
Glimepiride and Metformin
n=16 Participants
Protocol specified dosage and frequency of glimepiride + metformin for 12 weeks based on basal dose of metformin
|
|---|---|---|
|
Glycemic Variability Measured by Mean Amplitude of Glucose Excursions (MAGE)
|
6.68 mg/dL
Standard Deviation 1.48
|
6.23 mg/dL
Standard Deviation 1.08
|
SECONDARY outcome
Timeframe: Week 12Population: Analysis set includes all randomized patients excluding the ones who were prematurely withdrawn and the ones who have no data from visit 7 which required for comparison.
Continuous Overlapping Net Glycemic Action (CONGA) which assesses intra-day glycemic variability by calculating the difference between values at different intervals, adjusted according to requirements with the advantage of being highly reproducible. CONGA is calculated in the conventional way with the formula √tқΣt = t1 (Dt -Ď2) / қ - 1, Ď = tқ Σ Dt t = t1 / қ, Dt = Gt-Gt-m (where қ = Observations with an observation n x 60 minutes, G = glucose measure) from the data of continuous monitoring of tissue glucose obtained during the measurement period.
Outcome measures
| Measure |
Vildagliptin and Metformin
n=16 Participants
Based on basal dose of metformin, administration of vildagliptin/metformin 50 mg/850 mg twice daily (bid) or 50 mg/1000 mg bid for 12 weeks
|
Glimepiride and Metformin
n=16 Participants
Protocol specified dosage and frequency of glimepiride + metformin for 12 weeks based on basal dose of metformin
|
|---|---|---|
|
Glycemic Variability Measured by Continuous Overlapping Net Glycemic Action (CONGA)
|
2.92 mg/dL
Standard Deviation 0.93
|
3.01 mg/dL
Standard Deviation 1.10
|
SECONDARY outcome
Timeframe: Week 12Population: Analysis set includes all randomized patients excluding the ones who were prematurely withdrawn and the ones who have no data from visit 7 which required for comparison.
Total standard deviation (TSD) or standard deviation of all values of a given measurement period, which has the advantage of being able to include all measured values on a given time period (even several days) through a common and simple statistical concept. TSD is calculated conventionally with the formula σ = √Σ (Xi - ῦ) 2 / N (where Xi represents each of the values, ῦ represents the population mean and N is the number of observations) from the data of continuous monitoring of tissue glucose obtained during the measurement.
Outcome measures
| Measure |
Vildagliptin and Metformin
n=16 Participants
Based on basal dose of metformin, administration of vildagliptin/metformin 50 mg/850 mg twice daily (bid) or 50 mg/1000 mg bid for 12 weeks
|
Glimepiride and Metformin
n=16 Participants
Protocol specified dosage and frequency of glimepiride + metformin for 12 weeks based on basal dose of metformin
|
|---|---|---|
|
Glycemic Variability Measured by Total Standard Deviation (TSD)
|
1.36 mg/dL
Standard Deviation 0.40
|
1.40 mg/dL
Standard Deviation 0.42
|
SECONDARY outcome
Timeframe: Screening visit , 12 weeks of treatmentPopulation: Analysis set includes all randomized patients excluding the ones who were prematurely withdrawn and the ones who have confirmed non-concordant data
Outcome measures
| Measure |
Vildagliptin and Metformin
n=17 Participants
Based on basal dose of metformin, administration of vildagliptin/metformin 50 mg/850 mg twice daily (bid) or 50 mg/1000 mg bid for 12 weeks
|
Glimepiride and Metformin
n=17 Participants
Protocol specified dosage and frequency of glimepiride + metformin for 12 weeks based on basal dose of metformin
|
|---|---|---|
|
Percentage of Patients Who Achieved a Decrease Equal to or Greater Than 0.3% in Value of HbA1c at Week 12
|
100.0 percentage of patients
|
100.0 percentage of patients
|
SECONDARY outcome
Timeframe: baseline, 12 weeks of treatmentPopulation: Analysis set includes all randomized patients excluding the ones who were prematurely withdrawn and the ones who have confirmed non-concordant data
Outcome measures
| Measure |
Vildagliptin and Metformin
n=17 Participants
Based on basal dose of metformin, administration of vildagliptin/metformin 50 mg/850 mg twice daily (bid) or 50 mg/1000 mg bid for 12 weeks
|
Glimepiride and Metformin
n=17 Participants
Protocol specified dosage and frequency of glimepiride + metformin for 12 weeks based on basal dose of metformin
|
|---|---|---|
|
Change in HbA1c at Week 12 of Treatment in Comparison to HbA1c at Baseline
|
1.92 Percentage of glycosylated haemoglobin
Standard Deviation 1.1
|
2.28 Percentage of glycosylated haemoglobin
Standard Deviation 0.79
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Analysis set includes all randomized patients excluding the ones who were prematurely withdrawn and the ones who have no data from visit 7 which required for comparison.
Hypoglycemia defined as Glycemia \< 70 mg/dl
Outcome measures
| Measure |
Vildagliptin and Metformin
n=16 Participants
Based on basal dose of metformin, administration of vildagliptin/metformin 50 mg/850 mg twice daily (bid) or 50 mg/1000 mg bid for 12 weeks
|
Glimepiride and Metformin
n=16 Participants
Protocol specified dosage and frequency of glimepiride + metformin for 12 weeks based on basal dose of metformin
|
|---|---|---|
|
Number of Patients With Incidence of Hypoglycemia
|
1 Patients
|
4 Patients
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Analysis set includes all randomized patients excluding the ones who were prematurely withdrawn and the ones who have no data from visit 7 which required for comparison and had at least one hypoglycemia event.
MAGE , which determines the average blood glucose excursions either above or below a value of one standard deviation of the average value of glucose in a given day. MAGE is calculated from the data of continuous tissue glucose monitoring obtained during the measurement period. MAGE is calculated with the formula Σ λ / χ if λ\> ν (where λ = changes in blood glucose from peak to nadir, χ = number of valid observations, ν = 1 standard deviation of the mean glucose during a period of 24 hours) from the data of continuous monitoring of the tissue glucose, obtained during the period of measurement. In this endpoint, mean MAGE value is reported for hypo glycemic patients.
Outcome measures
| Measure |
Vildagliptin and Metformin
n=1 Participants
Based on basal dose of metformin, administration of vildagliptin/metformin 50 mg/850 mg twice daily (bid) or 50 mg/1000 mg bid for 12 weeks
|
Glimepiride and Metformin
n=4 Participants
Protocol specified dosage and frequency of glimepiride + metformin for 12 weeks based on basal dose of metformin
|
|---|---|---|
|
Mean Amplitude of Glycemic Excursions (MAGE) for Patients With Hypoglycemia Incidence After 12 Weeks of Treatment
|
5.23 mg/dL
Standard Deviation NA
Standard deviation is not measurable for one patient
|
5.53 mg/dL
Standard Deviation 0.82
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: All the randomized patients.
Outcome measures
| Measure |
Vildagliptin and Metformin
n=20 Participants
Based on basal dose of metformin, administration of vildagliptin/metformin 50 mg/850 mg twice daily (bid) or 50 mg/1000 mg bid for 12 weeks
|
Glimepiride and Metformin
n=20 Participants
Protocol specified dosage and frequency of glimepiride + metformin for 12 weeks based on basal dose of metformin
|
|---|---|---|
|
Number of Patients With Any Adverse Events, Serious Adverse Events and Death
Any adverse events (serious and non-serious)
|
9 Patients
|
13 Patients
|
|
Number of Patients With Any Adverse Events, Serious Adverse Events and Death
Serious Adverse Events
|
0 Patients
|
1 Patients
|
|
Number of Patients With Any Adverse Events, Serious Adverse Events and Death
Death
|
0 Patients
|
0 Patients
|
Adverse Events
Vildagliptin and Metformin
Glimepiride and Metformin
Serious adverse events
| Measure |
Vildagliptin and Metformin
n=20 participants at risk
Based on basal dose of metformin, administration of vildagliptin/metformin 50 mg/850 mg twice daily (bid) or 50 mg/1000 mg bid for 12 weeks
|
Glimepiride and Metformin
n=20 participants at risk
Protocol specified dosage and frequency of glimepiride + metformin for 12 weeks based on basal dose of metformin
|
|---|---|---|
|
Infections and infestations
Erysipelas
|
0.00%
0/20
|
5.0%
1/20
|
Other adverse events
| Measure |
Vildagliptin and Metformin
n=20 participants at risk
Based on basal dose of metformin, administration of vildagliptin/metformin 50 mg/850 mg twice daily (bid) or 50 mg/1000 mg bid for 12 weeks
|
Glimepiride and Metformin
n=20 participants at risk
Protocol specified dosage and frequency of glimepiride + metformin for 12 weeks based on basal dose of metformin
|
|---|---|---|
|
Cardiac disorders
Palpitations
|
0.00%
0/20
|
5.0%
1/20
|
|
Ear and labyrinth disorders
Ear pain
|
5.0%
1/20
|
0.00%
0/20
|
|
Ear and labyrinth disorders
Vertigo
|
5.0%
1/20
|
0.00%
0/20
|
|
Eye disorders
Cataract
|
0.00%
0/20
|
5.0%
1/20
|
|
Eye disorders
Eye irritation
|
5.0%
1/20
|
0.00%
0/20
|
|
Eye disorders
Eyelid oedema
|
5.0%
1/20
|
5.0%
1/20
|
|
Eye disorders
Presbyopia
|
0.00%
0/20
|
5.0%
1/20
|
|
Eye disorders
Refraction disorder
|
0.00%
0/20
|
5.0%
1/20
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/20
|
5.0%
1/20
|
|
Gastrointestinal disorders
Nausea
|
5.0%
1/20
|
0.00%
0/20
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/20
|
5.0%
1/20
|
|
General disorders
Asthenia
|
5.0%
1/20
|
0.00%
0/20
|
|
General disorders
Chest pain
|
0.00%
0/20
|
5.0%
1/20
|
|
General disorders
Hypothermia
|
5.0%
1/20
|
0.00%
0/20
|
|
General disorders
Influenza like illness
|
15.0%
3/20
|
5.0%
1/20
|
|
General disorders
Oedema
|
5.0%
1/20
|
0.00%
0/20
|
|
General disorders
Oedema peripheral
|
0.00%
0/20
|
5.0%
1/20
|
|
Hepatobiliary disorders
Jaundice
|
5.0%
1/20
|
0.00%
0/20
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/20
|
5.0%
1/20
|
|
Infections and infestations
Chikungunya virus infection
|
0.00%
0/20
|
5.0%
1/20
|
|
Infections and infestations
Onychomycosis
|
0.00%
0/20
|
5.0%
1/20
|
|
Infections and infestations
Rhinitis
|
0.00%
0/20
|
5.0%
1/20
|
|
Infections and infestations
Tinea pedis
|
0.00%
0/20
|
5.0%
1/20
|
|
Infections and infestations
Tooth abscess
|
0.00%
0/20
|
5.0%
1/20
|
|
Injury, poisoning and procedural complications
Bone fissure
|
0.00%
0/20
|
5.0%
1/20
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/20
|
5.0%
1/20
|
|
Injury, poisoning and procedural complications
Soft tissue injury
|
5.0%
1/20
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
Wound
|
0.00%
0/20
|
5.0%
1/20
|
|
Investigations
Blood pressure increased
|
0.00%
0/20
|
5.0%
1/20
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
5.0%
1/20
|
25.0%
5/20
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.0%
1/20
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.0%
1/20
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Costochondritis
|
0.00%
0/20
|
5.0%
1/20
|
|
Musculoskeletal and connective tissue disorders
Joint crepitation
|
0.00%
0/20
|
5.0%
1/20
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/20
|
5.0%
1/20
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/20
|
5.0%
1/20
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.0%
1/20
|
10.0%
2/20
|
|
Nervous system disorders
Dizziness
|
0.00%
0/20
|
5.0%
1/20
|
|
Nervous system disorders
Headache
|
10.0%
2/20
|
5.0%
1/20
|
|
Nervous system disorders
Hypoaesthesia
|
5.0%
1/20
|
0.00%
0/20
|
|
Nervous system disorders
Tremor
|
0.00%
0/20
|
15.0%
3/20
|
|
Renal and urinary disorders
Urine abnormality
|
0.00%
0/20
|
5.0%
1/20
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.00%
0/20
|
5.0%
1/20
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/20
|
5.0%
1/20
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract congestion
|
0.00%
0/20
|
5.0%
1/20
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/20
|
10.0%
2/20
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/20
|
5.0%
1/20
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/20
|
5.0%
1/20
|
|
Vascular disorders
Hypertension
|
5.0%
1/20
|
5.0%
1/20
|
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