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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Canagliflozin 300 mg; Drug: Sitagliptin 100 mg; Drug: Metformin

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 4

Contacts and Locations

Study Locations

• Mexico
  • Guadalajara, Mexico, 44150
    • Consultorio Privado
  • Guadalajara, Mexico, 44600
    • Investigación Clínica Especializada
  • Guadalajara, Mexico, 44650
    • Consultorio Privado en Unidad de Patología Clínica
  • Mexico City, Mexico, 14080
    • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
  • Monterrey, Mexico, 64460
    • Hospital Universitario 'Dr. Jose Eleuterio Gonzalez'

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 54 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment Sequence AB; Participants will receive 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. A washout period of at least 16 days (from Days 28 to 43) of metformin monotherapy will be maintained between each treatment period.	Drug: Canagliflozin 300 mg; Participants will receive canagliflozin 300 mg oral tablet once-daily for 28 days.; Other Names: JNJ-28431754; Drug: Sitagliptin 100 mg; Participants will receive sitagliptin 100 mg oral tablet once-daily for 28 days.; Drug: Metformin; Participants will receive metformin at a stable dose of >= 1500 mg/day throughout the study including the washout period between each intervention.
EXPERIMENTAL: Treatment Sequence BA; Participants will receive treatment B from Day 0 to 27 (treatment Period 1), followed by treatment A from Day 44 to 71 (treatment period 2), under fasted condition. A washout period of at least 16 days (from days 28 to 43) of metformin monotherapy will be maintained between each treatment period.	Drug: Canagliflozin 300 mg; Participants will receive canagliflozin 300 mg oral tablet once-daily for 28 days.; Other Names: JNJ-28431754; Drug: Sitagliptin 100 mg; Participants will receive sitagliptin 100 mg oral tablet once-daily for 28 days.; Drug: Metformin; Participants will receive metformin at a stable dose of >= 1500 mg/day throughout the study including the washout period between each intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline up to End of Treatment Period 1 (Days 22 to 27)
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.	Baseline up to End of Treatment Period 2 (Days 66 to 71)

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 27, 2017
• Primary Completion (ACTUAL): October 1, 2018
• Study Completion (ACTUAL): October 1, 2018

Study Registration Dates

• First Submitted: August 29, 2017
• First Submitted That Met QC Criteria: August 29, 2017
• First Posted (ACTUAL): August 30, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 29, 2019
• Last Update Submitted That Met QC Criteria: November 11, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Sitagliptin Phosphate; Canagliflozin
• Other Study ID Numbers: CR108346; 28431754DIA4026 (OTHER: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes