An Efficacy Study of Canagliflozin or Sitagliptin to Determine Glucose Variability in Mexican Participants With Type 2 Diabetes Mellitus Inadequately Controlled on Metformin

Canagliflozin Continuous Glucose Monitoring (CANA CGM) Trial: A Pilot Randomized, Double-Blind, Controlled, Crossover Study on the Effects of the SGLT-2 Inhibitor Canagliflozin (vs. the DPP-4 Inhibitor Sitagliptin) on Glucose Variability in Mexican Patients With Type 2 Diabetes Mellitus Inadequately Controlled on Metformin

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03267576

Acronym

COMETA

Enrollment

Registered

2017-08-30

Start date

2017-10-27

Completion date

2018-10-01

Last updated

2019-11-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes Mellitus, Type 2

Brief summary

The main purpose of this study is to assess the effects of 4 weeks each of daily treatment with canagliflozin 300 milligram (mg) versus sitagliptin 100 mg as treatment adjuncts to metformin (at stable dosages) on intrapatient glycemic coefficient of variation (CV), expressed as a ratio percentage of standard deviation (SD) to mean glucose levels.

Interventions

DRUGCanagliflozin 300 mg

Participants will receive canagliflozin 300 mg oral tablet once-daily for 28 days.

DRUGSitagliptin 100 mg

Participants will receive sitagliptin 100 mg oral tablet once-daily for 28 days.

DRUGMetformin

Participants will receive metformin at a stable dose of \>= 1500 mg/day throughout the study including the washout period between each intervention.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

19 Years to 54 Years

Healthy volunteers

Inclusion criteria

* Type 2 diabetes mellitus * Inadequate glucose control while using metformin monotherapy (MET) for at least 8 weeks at stable daily doses of at least 1500 milligram (mg) before screening visit (Visit 1) a. Hemoglobin A1c (HbA1c) equal to (=) 7.5 percent (%) to 10.5% at Visit 1 * Adequate qualifying continuous glucose monitoring (CGM) reading during the pre-randomization (selection) phase * Estimated glomerular filtration rate (eGFR) of at least 60 milliliter/minute (mL/min)/1.73 meter square (m\^2) at Visit 1 * Body mass index of 22 through 45 kilogram per meter square (kg/m\^2) at Visit 1

Exclusion criteria

* History of any of the following (at Visit 1): 1. Diabetic ketoacidosis (DKA) 2. Type 1 diabetes mellitus (T1DM) 3. Pancreatic (for example, Beta-islet cell) transplantation 4. Diabetes secondary to pancreatitis or pancreatectomy 5. Personal history of, or ongoing, pancreatitis 6. One or more episodes of severe hypoglycemia (requiring assistance from others), as documented in the history obtained at Visit 1 7. Hereditary glucose-galactose malabsorption or primary renal glucosuria * Repeated fasting plasma glucose (FPG) or fasting self-monitored blood glucose (SMBG) greater than (\>) 270 milligram per deciliter (mg/dL) during the pre-treatment phase * Treatment with any other oral or parenteral antidiabetic medications different from metformin monotherapy, including but not limited to Dipeptidyl peptidase-4 (DPP-4) inhibitors, Sulphonylureas, thiazolidinediones, insulins and Glucagon-like peptide-1 receptor agonist (GLP-1RAs); Sodium-glucose co-transporter 2 (SGLT-2) inhibitors and investigational agents * Received an investigational drug or vaccine or used an invasive investigational medical device within 30 days before the planned first dose of study drug * Current use of natural medicines or natural medicinal products for diabetes (for example, cactus-derived nutrients, celery)

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Glycemic Coefficient of Variation (CV) in Treatment Period 1	Baseline up to End of Treatment Period 1 (Days 22 to 27)	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.
Change From Baseline in Glycemic Coefficient of Variation (CV) in Treatment Period 2	Baseline up to End of Treatment Period 2 (Days 66 to 71)	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.

Secondary

Measure	Time frame	Description
Change From Baseline in Fasting Plasma Glucose Levels	Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)	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.
Change From Baseline in 2-hour Post-prandial Glucose (PPG) Levels	Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)	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.
Percent Change From Baseline in Time During 24 Hours With Glucose 70 to 139 mg/dL	Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)	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.
Percent Change From Baseline in Time During 24 Hours With Glucose Greater Than (>) 140 mg/dL	Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)	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.
Percent Change From Baseline in Time During 24 Hours With Glucose Level > 180 mg/dL	Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)	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.
Change From Baseline in Glycemic Standard Deviation (SD) for 24-hour Glucose Profile	Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)	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.
Change From Baseline in Time Spent With Glucose Level 70 to 139 mg/dL	Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)	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.
Change From Baseline in Time Spent With Glucose Level > 140 mg/dL	Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)	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.
Change From Baseline in Time Spent With Glucose Level > 180 mg/dL	Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)	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.
Change From Baseline in Time Spent With Glucose Level < 70 mg/dL	Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)	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.
Change From Baseline in Percentage of 2 Consecutive Glucose Readings With < 70 mg/dL	Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)	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.
Percent Change From Baseline in Time During 24 Hours With Glucose Level Less Than (<) 70 mg/dL	Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)	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.
Change From Baseline in Mean 24-hour Glucose Profile	Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)	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.

Countries

Mexico

Participant flow

Pre-assignment details

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.

Participants by arm

Arm	Count
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 16 days (from Days 28 to 43) along with continued metformin monotherapy.	31
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.	32
Total	63

Withdrawals & dropouts

Period	Reason	FG000	FG001
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

Characteristic	Treatment Sequence BA	Treatment Sequence AB	Total
Age, Continuous	44.84 Years STANDARD_DEVIATION 9.088	46.03 Years STANDARD_DEVIATION 6.237	45.3 Years STANDARD_DEVIATION 7.8
Height	1.64 Meter STANDARD_DEVIATION 0.1	1.63 Meter STANDARD_DEVIATION 0.1	1.63 Meter STANDARD_DEVIATION 0.1
Race/Ethnicity, Customized Afro-American	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Asian	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Caucasian	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Hispanic Mexican mestizo	32 Participants	31 Participants	63 Participants
Sex: Female, Male Female	14 Participants	14 Participants	28 Participants
Sex: Female, Male Male	18 Participants	17 Participants	35 Participants
Weight	88.96 Kilogram STANDARD_DEVIATION 14.17	84.01 Kilogram STANDARD_DEVIATION 15.86	86.52 Kilogram STANDARD_DEVIATION 15.11

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 63	0 / 63
other Total, other adverse events	7 / 63	2 / 63
serious Total, serious adverse events	0 / 63	0 / 63

Outcome results

Primary

Change From Baseline in Glycemic Coefficient of Variation (CV) in Treatment Period 1

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.

Time frame: 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).

Arm	Measure	Value (MEAN)	Dispersion
Treatment Sequence AB	Change From Baseline in Glycemic Coefficient of Variation (CV) in Treatment Period 1	-0.69 Percentage of CV	Standard Deviation 5.17
Treatment Sequence BA	Change From Baseline in Glycemic Coefficient of Variation (CV) in Treatment Period 1	0.24 Percentage of CV	Standard Deviation 10.23

Primary

Change From Baseline in Glycemic Coefficient of Variation (CV) in Treatment Period 2

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.

Time frame: 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).

Arm	Measure	Value (MEAN)	Dispersion
Treatment Sequence AB	Change From Baseline in Glycemic Coefficient of Variation (CV) in Treatment Period 2	-1.26 Percentage of CV	Standard Deviation 7.41
Treatment Sequence BA	Change From Baseline in Glycemic Coefficient of Variation (CV) in Treatment Period 2	0.77 Percentage of CV	Standard Deviation 6.16

Secondary

Change From Baseline in 2-hour Post-prandial Glucose (PPG) Levels

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.