Trial Outcomes & Findings for An Efficacy Study of Canagliflozin or Sitagliptin to Determine Glucose Variability in Mexican Participants With Type 2 Diabetes Mellitus Inadequately Controlled on Metformin (NCT NCT03267576)
NCT ID: NCT03267576
Last Updated: 2019-11-29
Results Overview
Continuous blood glucose monitoring was done in participants using continuous glucose monitoring (CGM) determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and after each active treatment. Glucose coefficient of variation (CV) was calculated based on CGM data dividing the standard deviation of blood glucose values by the mean of the corresponding glucose readings. The participants were analyzed according to treatment received in treatment period 2 as per the sequence reported in this outcome measure.
COMPLETED
PHASE4
64 participants
Baseline up to End of Treatment Period 1 (Days 22 to 27)
2019-11-29
Participant Flow
A total of 64 participants were enrolled in this study but 1 participant has withdrawn consent before assigning to any study treatment hence, 63 participants were randomized to study treatment arms.
Participant milestones
| Measure |
Treatment Sequence AB
Participants received metformin monotherapy at stable doses (greater than or equal to \[\>=\] 1500 milligram per day \[mg/day\]) orally once daily with canagliflozin 300 milligram (mg) tablet orally once daily (Treatment A) from Day 0 to 27 (treatment period 1), followed by sitagliptin 100 mg tablet orally once daily with metformin \>=1500 mg/day (Treatment B) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of at least 16 days (from Days 28 to 43) along with ongoing metformin monotherapy.
|
Treatment Sequence BA
Participants received metformin monotherapy at stable doses \>=1500 mg/day with sitagliptin 100 mg tablet orally once daily (Treatment B) from Day 0 to 27 (treatment Period 1), followed by metformin \>= 1500 mg/day orally once daily with canagliflozin 300 mg tablet orally once daily (Treatment A) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from days 28 to 43) along with ongoing metformin monotherapy.
|
|---|---|---|
|
Period 1: Day 0 to 27
STARTED
|
31
|
32
|
|
Period 1: Day 0 to 27
COMPLETED
|
31
|
32
|
|
Period 1: Day 0 to 27
NOT COMPLETED
|
0
|
0
|
|
Washout Period: 16 Days
STARTED
|
31
|
32
|
|
Washout Period: 16 Days
COMPLETED
|
31
|
32
|
|
Washout Period: 16 Days
NOT COMPLETED
|
0
|
0
|
|
Period 2: Day 44 to 71
STARTED
|
31
|
32
|
|
Period 2: Day 44 to 71
COMPLETED
|
30
|
30
|
|
Period 2: Day 44 to 71
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
Treatment Sequence AB
Participants received metformin monotherapy at stable doses (greater than or equal to \[\>=\] 1500 milligram per day \[mg/day\]) orally once daily with canagliflozin 300 milligram (mg) tablet orally once daily (Treatment A) from Day 0 to 27 (treatment period 1), followed by sitagliptin 100 mg tablet orally once daily with metformin \>=1500 mg/day (Treatment B) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of at least 16 days (from Days 28 to 43) along with ongoing metformin monotherapy.
|
Treatment Sequence BA
Participants received metformin monotherapy at stable doses \>=1500 mg/day with sitagliptin 100 mg tablet orally once daily (Treatment B) from Day 0 to 27 (treatment Period 1), followed by metformin \>= 1500 mg/day orally once daily with canagliflozin 300 mg tablet orally once daily (Treatment A) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from days 28 to 43) along with ongoing metformin monotherapy.
|
|---|---|---|
|
Period 2: Day 44 to 71
Lost to Follow-up
|
0
|
1
|
|
Period 2: Day 44 to 71
Withdrawal by Subject
|
1
|
1
|
Baseline Characteristics
An Efficacy Study of Canagliflozin or Sitagliptin to Determine Glucose Variability in Mexican Participants With Type 2 Diabetes Mellitus Inadequately Controlled on Metformin
Baseline characteristics by cohort
| Measure |
Treatment Sequence AB
n=31 Participants
Participants received metformin monotherapy at stable doses (greater than or equal to \[\>=\] 1500 milligram per day \[mg/day\]) orally once daily with canagliflozin 300 milligram (mg) tablet orally once daily (Treatment A) from Day 0 to 27 (treatment period 1), followed by sitagliptin 100 mg tablet orally once daily with metformin \>=1500 mg/day (Treatment B) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of at 16 days (from Days 28 to 43) along with continued metformin monotherapy.
|
Treatment Sequence BA
n=32 Participants
Participants received metformin monotherapy at stable doses \>=1500 mg/day with sitagliptin 100 mg tablet orally once daily (Treatment B) from Day 0 to 27 (treatment Period 1), followed by metformin \>= 1500 mg/day orally once daily with canagliflozin 300 mg tablet orally once daily (Treatment A) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from days 28 to 43) along with ongoing metformin monotherapy.
|
Total
n=63 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
46.03 Years
STANDARD_DEVIATION 6.237 • n=5 Participants
|
44.84 Years
STANDARD_DEVIATION 9.088 • n=7 Participants
|
45.3 Years
STANDARD_DEVIATION 7.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic Mexican mestizo
|
31 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
63 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Afro-American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Height
|
1.63 Meter
STANDARD_DEVIATION 0.10 • n=5 Participants
|
1.64 Meter
STANDARD_DEVIATION 0.10 • n=7 Participants
|
1.63 Meter
STANDARD_DEVIATION 0.10 • n=5 Participants
|
|
Weight
|
84.01 Kilogram
STANDARD_DEVIATION 15.86 • n=5 Participants
|
88.96 Kilogram
STANDARD_DEVIATION 14.17 • n=7 Participants
|
86.52 Kilogram
STANDARD_DEVIATION 15.11 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27)Population: Intent-to-treat (ITT) analysis set included all participants who received at least one dose of medication and in whom CGM recordings at baseline and after each active treatment were successful (greater than \[\>\] 70% of tracings available).
Continuous blood glucose monitoring was done in participants using continuous glucose monitoring (CGM) determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and after each active treatment. Glucose coefficient of variation (CV) was calculated based on CGM data dividing the standard deviation of blood glucose values by the mean of the corresponding glucose readings. The participants were analyzed according to treatment received in treatment period 2 as per the sequence reported in this outcome measure.
Outcome measures
| Measure |
Treatment Sequence BA
n=32 Participants
Participants received metformin monotherapy at stable doses \>=1500 mg/day with sitagliptin 100 mg tablet orally once daily (Treatment B) from Day 0 to 27 (treatment Period 1), followed by metformin \>= 1500 mg/day orally once daily with canagliflozin 300 mg tablet orally once daily (Treatment A) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from days 28 to 43) along with ongoing metformin monotherapy.
|
Treatment Sequence AB
n=31 Participants
Participants received metformin monotherapy at stable doses (greater than or equal to \[\>=\] 1500 milligram per day \[mg/day\]) orally once daily with canagliflozin 300 milligram (mg) tablet orally once daily (Treatment A) from Day 0 to 27 (treatment period 1), followed by sitagliptin 100 mg tablet orally once daily with metformin \>=1500 mg/day (Treatment B) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from Days 28 to 43) along with ongoing metformin monotherapy.
|
|---|---|---|
|
Change From Baseline in Glycemic Coefficient of Variation (CV) in Treatment Period 1
|
0.24 Percentage of CV
Standard Deviation 10.23
|
-0.69 Percentage of CV
Standard Deviation 5.17
|
PRIMARY outcome
Timeframe: Baseline up to End of Treatment Period 2 (Days 66 to 71)Population: ITT analysis set included all participants who received at least one dose of medication and in whom CGM recordings at baseline and after each active treatment were successful (\>70% of tracings available).
Continuous blood glucose monitoring was done in participants using CGM determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and after each active treatment. Glucose coefficient of variation was calculated based on CGM data dividing the standard deviation of blood glucose values by the mean of the corresponding glucose readings. The participants were analyzed according to treatment received in treatment period 2 as per the sequence reported in this outcome measure.
Outcome measures
| Measure |
Treatment Sequence BA
n=32 Participants
Participants received metformin monotherapy at stable doses \>=1500 mg/day with sitagliptin 100 mg tablet orally once daily (Treatment B) from Day 0 to 27 (treatment Period 1), followed by metformin \>= 1500 mg/day orally once daily with canagliflozin 300 mg tablet orally once daily (Treatment A) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from days 28 to 43) along with ongoing metformin monotherapy.
|
Treatment Sequence AB
n=31 Participants
Participants received metformin monotherapy at stable doses (greater than or equal to \[\>=\] 1500 milligram per day \[mg/day\]) orally once daily with canagliflozin 300 milligram (mg) tablet orally once daily (Treatment A) from Day 0 to 27 (treatment period 1), followed by sitagliptin 100 mg tablet orally once daily with metformin \>=1500 mg/day (Treatment B) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from Days 28 to 43) along with ongoing metformin monotherapy.
|
|---|---|---|
|
Change From Baseline in Glycemic Coefficient of Variation (CV) in Treatment Period 2
|
0.77 Percentage of CV
Standard Deviation 6.16
|
-1.26 Percentage of CV
Standard Deviation 7.41
|
SECONDARY outcome
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)Population: Per-protocol (PP) analysis set included all ITT participants without a major protocol violation, where ITT population included all participants who received at least one dose of medication and in whom CGM recordings at baseline and after each active treatment were successful.
Glycemic standard deviation for 24-hour glucose profile (glycemic variability), as measured by CGM was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants who received the study drug in the treatment period 1 and 2 as per the sequence were reported in this outcome measure.
Outcome measures
| Measure |
Treatment Sequence BA
n=32 Participants
Participants received metformin monotherapy at stable doses \>=1500 mg/day with sitagliptin 100 mg tablet orally once daily (Treatment B) from Day 0 to 27 (treatment Period 1), followed by metformin \>= 1500 mg/day orally once daily with canagliflozin 300 mg tablet orally once daily (Treatment A) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from days 28 to 43) along with ongoing metformin monotherapy.
|
Treatment Sequence AB
n=31 Participants
Participants received metformin monotherapy at stable doses (greater than or equal to \[\>=\] 1500 milligram per day \[mg/day\]) orally once daily with canagliflozin 300 milligram (mg) tablet orally once daily (Treatment A) from Day 0 to 27 (treatment period 1), followed by sitagliptin 100 mg tablet orally once daily with metformin \>=1500 mg/day (Treatment B) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from Days 28 to 43) along with ongoing metformin monotherapy.
|
|---|---|---|
|
Change From Baseline in Glycemic Standard Deviation (SD) for 24-hour Glucose Profile
Treatment Period 1
|
-8.40 mg/dL
Standard Deviation 11.07
|
-7.64 mg/dL
Standard Deviation 6.56
|
|
Change From Baseline in Glycemic Standard Deviation (SD) for 24-hour Glucose Profile
Treatment Period 2
|
-7.13 mg/dL
Standard Deviation 12.00
|
-8.53 mg/dL
Standard Deviation 10.35
|
SECONDARY outcome
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)Population: PP analysis set included all ITT participants without a major protocol violation, where ITT population included all participants who received at least one dose of medication and in whom CGM recordings at baseline and after each active treatment were successful.
Mean 24-hour glucose profiles as measured by CGM was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure.
Outcome measures
| Measure |
Treatment Sequence BA
n=32 Participants
Participants received metformin monotherapy at stable doses \>=1500 mg/day with sitagliptin 100 mg tablet orally once daily (Treatment B) from Day 0 to 27 (treatment Period 1), followed by metformin \>= 1500 mg/day orally once daily with canagliflozin 300 mg tablet orally once daily (Treatment A) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from days 28 to 43) along with ongoing metformin monotherapy.
|
Treatment Sequence AB
n=31 Participants
Participants received metformin monotherapy at stable doses (greater than or equal to \[\>=\] 1500 milligram per day \[mg/day\]) orally once daily with canagliflozin 300 milligram (mg) tablet orally once daily (Treatment A) from Day 0 to 27 (treatment period 1), followed by sitagliptin 100 mg tablet orally once daily with metformin \>=1500 mg/day (Treatment B) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from Days 28 to 43) along with ongoing metformin monotherapy.
|
|---|---|---|
|
Change From Baseline in Mean 24-hour Glucose Profile
Treatment Period 1
|
-39.56 mg/dL
Standard Deviation 39.79
|
-34.81 mg/dL
Standard Deviation 34.87
|
|
Change From Baseline in Mean 24-hour Glucose Profile
Treatment Period 2
|
-41.74 mg/dL
Standard Deviation 34.14
|
-31.27 mg/dL
Standard Deviation 33.27
|
SECONDARY outcome
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)Population: PP analysis set included all ITT participants without a major protocol violation, where ITT population included all participants who received at least one dose of medication and in whom CGM recordings at baseline and after each active treatment were successful.
Fasting plasma glucose levels were determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure.
Outcome measures
| Measure |
Treatment Sequence BA
n=32 Participants
Participants received metformin monotherapy at stable doses \>=1500 mg/day with sitagliptin 100 mg tablet orally once daily (Treatment B) from Day 0 to 27 (treatment Period 1), followed by metformin \>= 1500 mg/day orally once daily with canagliflozin 300 mg tablet orally once daily (Treatment A) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from days 28 to 43) along with ongoing metformin monotherapy.
|
Treatment Sequence AB
n=31 Participants
Participants received metformin monotherapy at stable doses (greater than or equal to \[\>=\] 1500 milligram per day \[mg/day\]) orally once daily with canagliflozin 300 milligram (mg) tablet orally once daily (Treatment A) from Day 0 to 27 (treatment period 1), followed by sitagliptin 100 mg tablet orally once daily with metformin \>=1500 mg/day (Treatment B) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from Days 28 to 43) along with ongoing metformin monotherapy.
|
|---|---|---|
|
Change From Baseline in Fasting Plasma Glucose Levels
Treatment Period 1
|
-34.48 mg/dL
Standard Deviation 32.94
|
-32.04 mg/dL
Standard Deviation 33.95
|
|
Change From Baseline in Fasting Plasma Glucose Levels
Treatment Period 2
|
-45.51 mg/dL
Standard Deviation 35.26
|
-27.69 mg/dL
Standard Deviation 32.19
|
SECONDARY outcome
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)Population: PP analysis set included all ITT participants without a major protocol violation, where ITT population included all participants who received at least one dose of medication and in whom CGM recordings at baseline and after each active treatment were successful.
2-hour post-prandial glucose levels were determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure.
Outcome measures
| Measure |
Treatment Sequence BA
n=32 Participants
Participants received metformin monotherapy at stable doses \>=1500 mg/day with sitagliptin 100 mg tablet orally once daily (Treatment B) from Day 0 to 27 (treatment Period 1), followed by metformin \>= 1500 mg/day orally once daily with canagliflozin 300 mg tablet orally once daily (Treatment A) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from days 28 to 43) along with ongoing metformin monotherapy.
|
Treatment Sequence AB
n=31 Participants
Participants received metformin monotherapy at stable doses (greater than or equal to \[\>=\] 1500 milligram per day \[mg/day\]) orally once daily with canagliflozin 300 milligram (mg) tablet orally once daily (Treatment A) from Day 0 to 27 (treatment period 1), followed by sitagliptin 100 mg tablet orally once daily with metformin \>=1500 mg/day (Treatment B) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from Days 28 to 43) along with ongoing metformin monotherapy.
|
|---|---|---|
|
Change From Baseline in 2-hour Post-prandial Glucose (PPG) Levels
Treatment Period 1
|
-43.36 mg/dL
Standard Deviation 48.00
|
-47.03 mg/dL
Standard Deviation 45.85
|
|
Change From Baseline in 2-hour Post-prandial Glucose (PPG) Levels
Treatment Period 2
|
-44.03 mg/dL
Standard Deviation 43.80
|
-41.12 mg/dL
Standard Deviation 44.77
|
SECONDARY outcome
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)Population: PP analysis set included all intent-to-treat participants without a major protocol violation, where ITT population included all participants who received at least one dose of medication and in whom CGM recordings at baseline and after each active treatment were successful.
Percent change from baseline in time during 24 hours with glucose levels 70 to 139 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure.
Outcome measures
| Measure |
Treatment Sequence BA
n=32 Participants
Participants received metformin monotherapy at stable doses \>=1500 mg/day with sitagliptin 100 mg tablet orally once daily (Treatment B) from Day 0 to 27 (treatment Period 1), followed by metformin \>= 1500 mg/day orally once daily with canagliflozin 300 mg tablet orally once daily (Treatment A) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from days 28 to 43) along with ongoing metformin monotherapy.
|
Treatment Sequence AB
n=31 Participants
Participants received metformin monotherapy at stable doses (greater than or equal to \[\>=\] 1500 milligram per day \[mg/day\]) orally once daily with canagliflozin 300 milligram (mg) tablet orally once daily (Treatment A) from Day 0 to 27 (treatment period 1), followed by sitagliptin 100 mg tablet orally once daily with metformin \>=1500 mg/day (Treatment B) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from Days 28 to 43) along with ongoing metformin monotherapy.
|
|---|---|---|
|
Percent Change From Baseline in Time During 24 Hours With Glucose 70 to 139 mg/dL
Treatment Period 1
|
0.191 Percent Change
Standard Deviation 0.224
|
0.157 Percent Change
Standard Deviation 0.134
|
|
Percent Change From Baseline in Time During 24 Hours With Glucose 70 to 139 mg/dL
Treatment Period 2
|
0.182 Percent Change
Standard Deviation 0.209
|
0.192 Percent Change
Standard Deviation 0.214
|
SECONDARY outcome
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)Population: PP analysis set included all ITT participants without a major protocol violation, where ITT population included all participants who received at least one dose of medication and in whom CGM recordings at baseline and after each active treatment were successful.
Percent change from baseline in time during 24 hours within the glucose levels \>140 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure.
Outcome measures
| Measure |
Treatment Sequence BA
n=32 Participants
Participants received metformin monotherapy at stable doses \>=1500 mg/day with sitagliptin 100 mg tablet orally once daily (Treatment B) from Day 0 to 27 (treatment Period 1), followed by metformin \>= 1500 mg/day orally once daily with canagliflozin 300 mg tablet orally once daily (Treatment A) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from days 28 to 43) along with ongoing metformin monotherapy.
|
Treatment Sequence AB
n=31 Participants
Participants received metformin monotherapy at stable doses (greater than or equal to \[\>=\] 1500 milligram per day \[mg/day\]) orally once daily with canagliflozin 300 milligram (mg) tablet orally once daily (Treatment A) from Day 0 to 27 (treatment period 1), followed by sitagliptin 100 mg tablet orally once daily with metformin \>=1500 mg/day (Treatment B) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from Days 28 to 43) along with ongoing metformin monotherapy.
|
|---|---|---|
|
Percent Change From Baseline in Time During 24 Hours With Glucose Greater Than (>) 140 mg/dL
Treatment Period 1
|
-0.216 Percent Change
Standard Deviation 0.257
|
-0.161 Percent Change
Standard Deviation 0.145
|
|
Percent Change From Baseline in Time During 24 Hours With Glucose Greater Than (>) 140 mg/dL
Treatment Period 2
|
-0.221 Percent Change
Standard Deviation 0.210
|
-214 Percent Change
Standard Deviation 0.237
|
SECONDARY outcome
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)Population: PP analysis set included all ITT participants without a major protocol violation, where ITT population included all participants who received at least one dose of medication and in whom CGM recordings at baseline and after each active treatment were successful.
Percent change from baseline in time during 24 hours within the glucose levels \>180 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 as per the sequence reported in this outcome measure.
Outcome measures
| Measure |
Treatment Sequence BA
n=32 Participants
Participants received metformin monotherapy at stable doses \>=1500 mg/day with sitagliptin 100 mg tablet orally once daily (Treatment B) from Day 0 to 27 (treatment Period 1), followed by metformin \>= 1500 mg/day orally once daily with canagliflozin 300 mg tablet orally once daily (Treatment A) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from days 28 to 43) along with ongoing metformin monotherapy.
|
Treatment Sequence AB
n=31 Participants
Participants received metformin monotherapy at stable doses (greater than or equal to \[\>=\] 1500 milligram per day \[mg/day\]) orally once daily with canagliflozin 300 milligram (mg) tablet orally once daily (Treatment A) from Day 0 to 27 (treatment period 1), followed by sitagliptin 100 mg tablet orally once daily with metformin \>=1500 mg/day (Treatment B) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from Days 28 to 43) along with ongoing metformin monotherapy.
|
|---|---|---|
|
Percent Change From Baseline in Time During 24 Hours With Glucose Level > 180 mg/dL
Treatment Period 1
|
-0.212 Percent Change
Standard Deviation 0.286
|
-0.235 Percent Change
Standard Deviation 0.204
|
|
Percent Change From Baseline in Time During 24 Hours With Glucose Level > 180 mg/dL
Treatment Period 2
|
-0.251 Percent Change
Standard Deviation 0.249
|
-0.246 Percent Change
Standard Deviation 0.232
|
SECONDARY outcome
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)Population: PP analysis set included all ITT participants without a major protocol violation, where ITT population included all participants who received at least one dose of medication and in whom CGM recordings at baseline and after each active treatment were successful.
Percent change from baseline in time during 24 hours within the glucose levels \< 70 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure.
Outcome measures
| Measure |
Treatment Sequence BA
n=32 Participants
Participants received metformin monotherapy at stable doses \>=1500 mg/day with sitagliptin 100 mg tablet orally once daily (Treatment B) from Day 0 to 27 (treatment Period 1), followed by metformin \>= 1500 mg/day orally once daily with canagliflozin 300 mg tablet orally once daily (Treatment A) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from days 28 to 43) along with ongoing metformin monotherapy.
|
Treatment Sequence AB
n=31 Participants
Participants received metformin monotherapy at stable doses (greater than or equal to \[\>=\] 1500 milligram per day \[mg/day\]) orally once daily with canagliflozin 300 milligram (mg) tablet orally once daily (Treatment A) from Day 0 to 27 (treatment period 1), followed by sitagliptin 100 mg tablet orally once daily with metformin \>=1500 mg/day (Treatment B) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from Days 28 to 43) along with ongoing metformin monotherapy.
|
|---|---|---|
|
Percent Change From Baseline in Time During 24 Hours With Glucose Level Less Than (<) 70 mg/dL
Treatment Period 1
|
NA Percent Change
Standard Deviation NA
Here, NA signifies that data could not be calculated since there were \<5 cases with valid observations of glycemic readings \<70 mg/dL.
|
NA Percent Change
Standard Deviation NA
Here, NA signifies that data could not be calculated since there were \<5 cases with valid observations of glycemic readings \<70 mg/dL.
|
|
Percent Change From Baseline in Time During 24 Hours With Glucose Level Less Than (<) 70 mg/dL
Treatment Period 2
|
NA Percent Change
Standard Deviation NA
Here, NA signifies that data could not be calculated since there were \<5 cases with valid observations of glycemic readings \<70 mg/dL.
|
NA Percent Change
Standard Deviation NA
Here, NA signifies that data could not be calculated since there were \<5 cases with valid observations of glycemic readings \<70 mg/dL.
|
SECONDARY outcome
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)Population: PP analysis set included all ITT participants without a major protocol violation, where ITT population included all participants who received at least one dose of medication and in whom CGM recordings at baseline and after each active treatment were successful.
Time spent with the glucose level 70 to 139 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure.
Outcome measures
| Measure |
Treatment Sequence BA
n=32 Participants
Participants received metformin monotherapy at stable doses \>=1500 mg/day with sitagliptin 100 mg tablet orally once daily (Treatment B) from Day 0 to 27 (treatment Period 1), followed by metformin \>= 1500 mg/day orally once daily with canagliflozin 300 mg tablet orally once daily (Treatment A) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from days 28 to 43) along with ongoing metformin monotherapy.
|
Treatment Sequence AB
n=31 Participants
Participants received metformin monotherapy at stable doses (greater than or equal to \[\>=\] 1500 milligram per day \[mg/day\]) orally once daily with canagliflozin 300 milligram (mg) tablet orally once daily (Treatment A) from Day 0 to 27 (treatment period 1), followed by sitagliptin 100 mg tablet orally once daily with metformin \>=1500 mg/day (Treatment B) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from Days 28 to 43) along with ongoing metformin monotherapy.
|
|---|---|---|
|
Change From Baseline in Time Spent With Glucose Level 70 to 139 mg/dL
Treatment Period 1
|
275.64 Minutes
Standard Deviation 323.39
|
226.64 Minutes
Standard Deviation 193.01
|
|
Change From Baseline in Time Spent With Glucose Level 70 to 139 mg/dL
Treatment Period 2
|
261.57 Minutes
Standard Deviation 301.75
|
277.00 Minutes
Standard Deviation 309.46
|
SECONDARY outcome
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)Population: PP analysis set included all ITT participants without a major protocol violation, where ITT population included all participants who received at least one dose of medication and in whom CGM recordings at baseline and after each active treatment were successful.
Time spent with the glucose level \> 140 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure.
Outcome measures
| Measure |
Treatment Sequence BA
n=32 Participants
Participants received metformin monotherapy at stable doses \>=1500 mg/day with sitagliptin 100 mg tablet orally once daily (Treatment B) from Day 0 to 27 (treatment Period 1), followed by metformin \>= 1500 mg/day orally once daily with canagliflozin 300 mg tablet orally once daily (Treatment A) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from days 28 to 43) along with ongoing metformin monotherapy.
|
Treatment Sequence AB
n=31 Participants
Participants received metformin monotherapy at stable doses (greater than or equal to \[\>=\] 1500 milligram per day \[mg/day\]) orally once daily with canagliflozin 300 milligram (mg) tablet orally once daily (Treatment A) from Day 0 to 27 (treatment period 1), followed by sitagliptin 100 mg tablet orally once daily with metformin \>=1500 mg/day (Treatment B) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from Days 28 to 43) along with ongoing metformin monotherapy.
|
|---|---|---|
|
Change From Baseline in Time Spent With Glucose Level > 140 mg/dL
Treatment Period 1
|
-310.41 Minutes
Standard Deviation 370.20
|
-231.98 Minutes
Standard Deviation 208.27
|
|
Change From Baseline in Time Spent With Glucose Level > 140 mg/dL
Treatment Period 2
|
318.23 Minutes
Standard Deviation 303.02
|
-308.68 Minutes
Standard Deviation 341.00
|
SECONDARY outcome
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)Population: PP analysis set included all ITT participants without a major protocol violation, where ITT population included all participants who received at least one dose of medication and in whom CGM recordings at baseline and after each active treatment were successful.
Time spent with the glucose level \> 180 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 as per the sequence reported in this outcome measure.
Outcome measures
| Measure |
Treatment Sequence BA
n=32 Participants
Participants received metformin monotherapy at stable doses \>=1500 mg/day with sitagliptin 100 mg tablet orally once daily (Treatment B) from Day 0 to 27 (treatment Period 1), followed by metformin \>= 1500 mg/day orally once daily with canagliflozin 300 mg tablet orally once daily (Treatment A) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from days 28 to 43) along with ongoing metformin monotherapy.
|
Treatment Sequence AB
n=31 Participants
Participants received metformin monotherapy at stable doses (greater than or equal to \[\>=\] 1500 milligram per day \[mg/day\]) orally once daily with canagliflozin 300 milligram (mg) tablet orally once daily (Treatment A) from Day 0 to 27 (treatment period 1), followed by sitagliptin 100 mg tablet orally once daily with metformin \>=1500 mg/day (Treatment B) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from Days 28 to 43) along with ongoing metformin monotherapy.
|
|---|---|---|
|
Change From Baseline in Time Spent With Glucose Level > 180 mg/dL
Treatment Period 1
|
-305.69 Minutes
Standard Deviation 412.30
|
-338.36 Minutes
Standard Deviation 293.40
|
|
Change From Baseline in Time Spent With Glucose Level > 180 mg/dL
Treatment Period 2
|
-361.65 Minutes
Standard Deviation 358.27
|
-354.63 Minutes
Standard Deviation 333.52
|
SECONDARY outcome
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)Population: PP analysis set included all ITT participants without a major protocol violation, where ITT population included all participants who received at least one dose of medication and in whom CGM recordings at baseline and after each active treatment were successful.
Time spent with the glucose level \< 70 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure.
Outcome measures
| Measure |
Treatment Sequence BA
n=32 Participants
Participants received metformin monotherapy at stable doses \>=1500 mg/day with sitagliptin 100 mg tablet orally once daily (Treatment B) from Day 0 to 27 (treatment Period 1), followed by metformin \>= 1500 mg/day orally once daily with canagliflozin 300 mg tablet orally once daily (Treatment A) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from days 28 to 43) along with ongoing metformin monotherapy.
|
Treatment Sequence AB
n=31 Participants
Participants received metformin monotherapy at stable doses (greater than or equal to \[\>=\] 1500 milligram per day \[mg/day\]) orally once daily with canagliflozin 300 milligram (mg) tablet orally once daily (Treatment A) from Day 0 to 27 (treatment period 1), followed by sitagliptin 100 mg tablet orally once daily with metformin \>=1500 mg/day (Treatment B) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from Days 28 to 43) along with ongoing metformin monotherapy.
|
|---|---|---|
|
Change From Baseline in Time Spent With Glucose Level < 70 mg/dL
Treatment Period 1
|
NA Minutes
Standard Deviation NA
Here, NA signifies that data could not be calculated since there were \<5 cases with valid observations of glycemic readings \<70 mg/dL.
|
NA Minutes
Standard Deviation NA
Here, NA signifies that data could not be calculated since there were \<5 cases with valid observations of glycemic readings \<70 mg/dL.
|
|
Change From Baseline in Time Spent With Glucose Level < 70 mg/dL
Treatment Period 2
|
NA Minutes
Standard Deviation NA
Here, NA signifies that data could not be calculated since there were \<5 cases with valid observations of glycemic readings \<70 mg/dL.
|
NA Minutes
Standard Deviation NA
Here, NA signifies that data could not be calculated since there were \<5 cases with valid observations of glycemic readings \<70 mg/dL.
|
SECONDARY outcome
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)Population: PP analysis set included all ITT participants without a major protocol violation, where ITT population included all participants who received at least one dose of medication and in whom CGM recordings at baseline and after each active treatment were successful.
The percentage of 2 consecutive glucose readings with \< 70 mg/dL were reported. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure.
Outcome measures
| Measure |
Treatment Sequence BA
n=32 Participants
Participants received metformin monotherapy at stable doses \>=1500 mg/day with sitagliptin 100 mg tablet orally once daily (Treatment B) from Day 0 to 27 (treatment Period 1), followed by metformin \>= 1500 mg/day orally once daily with canagliflozin 300 mg tablet orally once daily (Treatment A) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from days 28 to 43) along with ongoing metformin monotherapy.
|
Treatment Sequence AB
n=31 Participants
Participants received metformin monotherapy at stable doses (greater than or equal to \[\>=\] 1500 milligram per day \[mg/day\]) orally once daily with canagliflozin 300 milligram (mg) tablet orally once daily (Treatment A) from Day 0 to 27 (treatment period 1), followed by sitagliptin 100 mg tablet orally once daily with metformin \>=1500 mg/day (Treatment B) from Day 44 to 71 (treatment period 2), under fasted condition with a washout period of 16 days (from Days 28 to 43) along with ongoing metformin monotherapy.
|
|---|---|---|
|
Change From Baseline in Percentage of 2 Consecutive Glucose Readings With < 70 mg/dL
Treatment Period 1
|
NA Percentage of readings
Standard Deviation NA
Here, NA signifies that data could not be calculated since there were \<5 cases with valid observations of glycemic readings \<70 mg/dL.
|
NA Percentage of readings
Standard Deviation NA
Here, NA signifies that data could not be calculated since there were \<5 cases with valid observations of glycemic readings \<70 mg/dL.
|
|
Change From Baseline in Percentage of 2 Consecutive Glucose Readings With < 70 mg/dL
Treatment Period 2
|
NA Percentage of readings
Standard Deviation NA
Here, NA signifies that data could not be calculated since there were \<5 cases with valid observations of glycemic readings \<70 mg/dL.
|
NA Percentage of readings
Standard Deviation NA
Here, NA signifies that data could not be calculated since there were \<5 cases with valid observations of glycemic readings \<70 mg/dL.
|
Adverse Events
Canagliflozin 300 mg
Sitagliptin 100 mg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Canagliflozin 300 mg
n=63 participants at risk
Participants received metformin monotherapy at stable doses (greater than or equal to \[\>=\] 1500 milligram per day \[mg/day\]) orally once daily with canagliflozin 300 milligram (mg) tablet orally once daily (Treatment A) under fasted condition.
|
Sitagliptin 100 mg
n=63 participants at risk
Participants received metformin monotherapy at stable doses \>= 1500 milligram mg/day orally once daily with sitagliptin 100 mg tablet orally once daily (Treatment B) under fasted condition.
|
|---|---|---|
|
Cardiac disorders
Tachycardia
|
1.6%
1/63 • Up to 96 Days
Adverse events (AEs) reported are when they occurred under the actual treatment group they were receiving at the AE and not by the randomized sequence. Safety population included all randomized participants who received at least 1 dose of study agent.
|
0.00%
0/63 • Up to 96 Days
Adverse events (AEs) reported are when they occurred under the actual treatment group they were receiving at the AE and not by the randomized sequence. Safety population included all randomized participants who received at least 1 dose of study agent.
|
|
Gastrointestinal disorders
Diarrhoea
|
1.6%
1/63 • Up to 96 Days
Adverse events (AEs) reported are when they occurred under the actual treatment group they were receiving at the AE and not by the randomized sequence. Safety population included all randomized participants who received at least 1 dose of study agent.
|
0.00%
0/63 • Up to 96 Days
Adverse events (AEs) reported are when they occurred under the actual treatment group they were receiving at the AE and not by the randomized sequence. Safety population included all randomized participants who received at least 1 dose of study agent.
|
|
Gastrointestinal disorders
Vomiting
|
1.6%
1/63 • Up to 96 Days
Adverse events (AEs) reported are when they occurred under the actual treatment group they were receiving at the AE and not by the randomized sequence. Safety population included all randomized participants who received at least 1 dose of study agent.
|
0.00%
0/63 • Up to 96 Days
Adverse events (AEs) reported are when they occurred under the actual treatment group they were receiving at the AE and not by the randomized sequence. Safety population included all randomized participants who received at least 1 dose of study agent.
|
|
General disorders
Discomfort
|
1.6%
1/63 • Up to 96 Days
Adverse events (AEs) reported are when they occurred under the actual treatment group they were receiving at the AE and not by the randomized sequence. Safety population included all randomized participants who received at least 1 dose of study agent.
|
0.00%
0/63 • Up to 96 Days
Adverse events (AEs) reported are when they occurred under the actual treatment group they were receiving at the AE and not by the randomized sequence. Safety population included all randomized participants who received at least 1 dose of study agent.
|
|
General disorders
Fatigue
|
3.2%
2/63 • Up to 96 Days
Adverse events (AEs) reported are when they occurred under the actual treatment group they were receiving at the AE and not by the randomized sequence. Safety population included all randomized participants who received at least 1 dose of study agent.
|
0.00%
0/63 • Up to 96 Days
Adverse events (AEs) reported are when they occurred under the actual treatment group they were receiving at the AE and not by the randomized sequence. Safety population included all randomized participants who received at least 1 dose of study agent.
|
|
Infections and infestations
Influenza
|
1.6%
1/63 • Up to 96 Days
Adverse events (AEs) reported are when they occurred under the actual treatment group they were receiving at the AE and not by the randomized sequence. Safety population included all randomized participants who received at least 1 dose of study agent.
|
0.00%
0/63 • Up to 96 Days
Adverse events (AEs) reported are when they occurred under the actual treatment group they were receiving at the AE and not by the randomized sequence. Safety population included all randomized participants who received at least 1 dose of study agent.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
1.6%
1/63 • Up to 96 Days
Adverse events (AEs) reported are when they occurred under the actual treatment group they were receiving at the AE and not by the randomized sequence. Safety population included all randomized participants who received at least 1 dose of study agent.
|
0.00%
0/63 • Up to 96 Days
Adverse events (AEs) reported are when they occurred under the actual treatment group they were receiving at the AE and not by the randomized sequence. Safety population included all randomized participants who received at least 1 dose of study agent.
|
|
Nervous system disorders
Headache
|
0.00%
0/63 • Up to 96 Days
Adverse events (AEs) reported are when they occurred under the actual treatment group they were receiving at the AE and not by the randomized sequence. Safety population included all randomized participants who received at least 1 dose of study agent.
|
1.6%
1/63 • Up to 96 Days
Adverse events (AEs) reported are when they occurred under the actual treatment group they were receiving at the AE and not by the randomized sequence. Safety population included all randomized participants who received at least 1 dose of study agent.
|
|
Vascular disorders
Hypertension
|
0.00%
0/63 • Up to 96 Days
Adverse events (AEs) reported are when they occurred under the actual treatment group they were receiving at the AE and not by the randomized sequence. Safety population included all randomized participants who received at least 1 dose of study agent.
|
1.6%
1/63 • Up to 96 Days
Adverse events (AEs) reported are when they occurred under the actual treatment group they were receiving at the AE and not by the randomized sequence. Safety population included all randomized participants who received at least 1 dose of study agent.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
- Publication restrictions are in place
Restriction type: OTHER