The Clinical Study to Assess the Effect of the Amount of Carbohydrate Intake and Meals Differing in Glycemic Index (GI) in Patients Treated With a Sodium-dependent Glucose Cotransporter 2 (SGLT2) Inhibitor
Condition: Diabetes Melltius, Type 2
Study type: Interventional

Summary: 
      The objectives of this clinical study is to assess the effect of the amount of carbohydrate
      intake and meals differing in glycemic index (GI) in patients of type 2 diabetes mellitus
      treated with an SGLT2 inhibitor (Luseogliflozin), which inhibits glucose reabsorption from
      renal uriniferous tubule, on glucose variability by using continuous glucose monitoring
      (CGM), and to establish dietary therapy which reduces the risk of hypoglycemia in patients
      treated with SGLT2 inhibitors. In addition, blood and urine samples are collected for
      metabolome analysis that will be performed as an extension study of the clinical study.
    

Detailed description: 
      <Background and Rationale> In order to decrease the risk of hypoglycemia caused by SGLT2
      inhibitor, it is necessary to review the effect of the volume of carbohydrate intake and the
      level of GI value on variation of blood glucose.

      Also, if a patient with chronic lack of carbohydrate intake receives SGLT2 inhibitors, there
      is a risk of serious hypoglycemic reaction. Thus, the establishment of proper meal for
      patients receiving SGLT2 inhibitors is the urgent task.

      The objective of this study is to establish a safe dietary therapy for patients with type 2
      diabetes mellitus to avoid hypoglycemia by controlling carbohydrate intake volume and GI
      value, where study patients are provided study meal three times a day and circadian blood
      glucose variation including blood glucose after meal is measured by using CGM.

      In addition, blood and urine samples are collected for the future research (metabolome
      analysis) on the effect of carbohydrate intake volume and GI value on metabolism to be
      conducted as an extended study of this study.

      <Study Procedures> Total of 24 study patients with type 2 diabetes mellitus who have not
      taken or washed out hypoglycemic drug (oral hypoglycemic drug and glucagon like peptide-1
      receptor agonist) for at least 4 weeks are randomized into 3 groups (8 patients each) of high
      GI meal containing 55% carbohydrate group, low GI meal containing 55% carbohydrate group, and
      high GI meal containing 40% carbohydrate group. The energy intake of study patients in all
      the groups is 1800 kcal per day. Each study group patient takes the following diets for 14
      days; study patients in high GI meal containing 55% carbohydrate group take 55% carbohydrate
      white rice diet; those in low GI meal containing 55% carbohydrate group take 55% carbohydrate
      brown rice diet; those in high GI meal containing 40% carbohydrate group take 40%
      carbohydrate white rice diet. Study patients orally receive luseogliflozin 2.5 mg s.i.d.
      before breakfast for 7 days from the 8th day of starting the study meal to the 14th day.

      Planned examinations are conducted at the initiation of the study meal, the initiation of the
      study treatment, and the completion of the clinical study. Blood glucose is measured on 4
      days from the 3rd day of the initiation of the study meal to pre-dose of study treatment and
      from 2 days before study treatment completion to the next day of study treatment so that
      blood glucose data of continuous 48 hours at one time can be obtained.

      <Time and process of getting informed consents> Principal investigator or sub-investigator
      fully explains the clinical study to candidate patients using informed consent form approved
      by the Institutional Review Board prior to the study procedure and obtains written informed
      consent from subjects on voluntary basis after confirming that patients duly understand the
      content of the clinical study. Principal investigator or sub-investigator who gives
      explanation to patients and study patients affix a name and seal or give a signature and
      enter the date on the informed consent form. If study collaborator gives supplementary
      explanation, the collaborator also affixes a name and seal or give a signature and enter the
      date.

      Principal investigator or sub-investigator provided the copy of the informed consent form to
      study patients who gave informed consent to participate in the clinical study and record
      them.

      Principal investigator or sub-investigator documents the date of informed consent on case
      report form.

      <Screening Examination> The eligibility for the clinical study of candidate patients who gave
      written informed consent are judged through the following examinations.

      Candidate patients undergo screening examinations between 28 days and one day before the
      initiation of test meal (if the patient takes one hypoglycemic drug, between 28 days and one
      day before the initiation of washout).

      Demographic background: date of birth, race, sex, disease duration of type 2 diabetes
      mellitus, drug and therapy used for treatment of type 2 diabetes mellitus within 3 months
      prior to the study procedure, complications / medical history, concomitant drug / therapy,
      drinking / smoking status, height / weight / BMI Examination item: physical examination,
      measurement of body fluid volume (by impedance method), clinical laboratory tests, vital
      signs (blood pressure, pulse rate, body temperature) <Statistical Analysis>

        1. Demographic and Other Baseline Characteristics Efficacy analysis set and Safety analysis
           set are used for the analysis. For discrete values, frequency is summarized by group;
           for continuous data, summary statistics is calculated. Comparison between groups is also
           conducted.

        2. Analysis of primary endpoint (Efficacy endpoint) Efficacy analysis set is used for the
           analysis. Summary statistics of blood glucose level by using CGM is calculated.
           Comparison between groups is also conducted.

        3. Analysis of Secondary endpoint (Safety endpoint or efficacy endpoint) Safety analysis
           set and Efficacy analysis set are used for the analysis and the followings are
           summarized and analyzed.

           For discrete values of clinical laboratory tests and vital signs, frequency is
           summarized by group; for continuous data, summary statistics is calculated by group.

           Summary statistics of adverse event is calculated by group.

        4. Significance level of test and confidence coefficient of confidence interval Tests are
           two-sided with the significance level of 5%. Confidence intervals are estimated with
           coefficient of 95%. <Sample size> Determination of sample size 24 patients (8 for each
           group) The sample size is 8 patients for each group because the size is operable and
           appropriate for analysis for the study.

      <Action to be taken to study patients when an adverse event occurs> If an adverse event is
      observed, principal investigator or sub-investigator provides treatment or follow-up to the
      study patients until the patient recovers from the adverse event or the follow-up is judged
      to be unneccesary by medically explainable reason. If follow-up examination, additional
      examination, or re-examination is necessary, they are conducted after obtaining the study
      patient's informed consent.

      Principal investigator or sub-investigator documents the name of adverse event, date of
      occurrence, intensity, seriousness, study drug adjustment, treatment for the adverse event,
      outcome, date of outcome, and relationship with the clinical study. For an adverse event
      which is observed from the initiation of the study drug administration to follow-up
      examination, the relationship with the study drug is also documented.
    

Intervention name(s): Luseogliflozin; Meal containing different carbohydrate ratio and GI value
Intervention type(s): Drug; Other
Intervention description(s): Study patients orally receive luseogliflozin 2.5 mg s.i.d. before breakfast for 7 days from the 8th day of starting the study meal to the 14th day.; High GI meal containing 55% carbohydrate Low GI meal containing 55% carbohydrate High GI meal containing 40% carbohydrate
Other intervention name(s): Lusefi tab. 2.5mg
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment