An Exploratory Study of the Effects of Trelagliptin and Alogliptin on Glucose Variability in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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This is a multi-center, randomized, open-label, parallel-group comparative, exploratory study to evaluate the effect of trelagliptin administered at a dose of 100 mg once weekly or alogliptin administered at a dose of 25 mg once daily for 4 weeks on glycemic variation in patients with type 2 diabetes mellitus using continuous glucose monitoring (CGM).

Detailed Description
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The purpose of this study is to evaluate the effect of trelagliptin administered orally at a dose of 100 mg once weekly or alogliptin administered orally at a dose of 25 mg once daily for 4 weeks on glycemic variation in an exploratory manner as a primary objective and to evaluate the effect of difference method of administration of Dipeptidyl-peptidase (DPP)-4 on glycemic variation as secondary objective.

Official Title
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An Exploratory Study to Evaluate the Effects of Trelagliptin and Alogliptin by CGM on Glucose Variability for One Week in Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Trelagliptin
* Drug: Alogliptin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who, in the opinion of the principal investigator or the investigator, are capable of understanding the content of the clinical research and complying with the research protocol requirements. Participants who are able to sign and date the informed consent form and information sheet prior to the start of study procedures. Participants diagnosed with type 2 diabetes mellitus. Participants with a glycated hemoglobin (HbA1c) [National Glycohemoglobin Standardization Program (NGSP value)] value ≥ 6.5% and < 8.5% at the start of the observation period (Day -2). Participants who experience a ≤ ±1.0% change in HbA1c (NGSP value) at the start of the observation period (Day -2) as compared with an HbA1c value obtained during the preceding 6 weeks. Participants receiving stable dietetic therapy and exercise therapy (if performed) for ≥ 4 weeks before the start of the observation period. Participants, who in the opinion of the principal investigator or the investigator, does not have to change (including discontinuation or interruption) 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors or add new HMG-CoA reductase inhibitors during treatment period. Men or women aged 20 years or older at the time of informed consent. Exclusion Criteria: Participants who received anti-diabetic medications within 4 weeks prior to the start of the observation period. Participants who have changed (including discontinuation or interruption) HMG-CoA reductase inhibitors or received new HMG-CoA reductase inhibitors ≤ 4 weeks before the start of the observation period. Participants with clinically evident hepatic dysfunction (e.g., aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 2.5-fold the upper limit of normal at the start of the observation period [Day -2]). Participants with moderate renal dysfunction, severe renal dysfunction or renal failure (e.g., creatinine clearance < 50 mL/min or serum creatinine > 1.4 mg/dL in men or > 1.2 mg/dL in women [equivalent to the creatinine clearance for persons aged 60 years with a body weight of 65 kg] at the start of the observation period [Day -2]). Participants with severe heart disease, cerebrovascular disorder, or severe pancreatic, hematologic or other diseases. Participants with a history of gastric or small intestinal resection. Participants with proliferative diabetic retinopathy. Participants warranting insulin therapy for glycemic control (e.g., participants with severe ketosis, diabetic coma or precoma, type 1 diabetes mellitus, severe infection, perioperative participants, or serious trauma). Participants with a history of hypersensitivity or allergy to DPP-4 inhibitors. Participants who experience an allergic reaction to metal during CGM at the start of the observation period (Day -2). Participants with any malignant tumors. Habitual drinkers whose average daily alcohol consumption is > 100 mL. Participants who have any contraindications for the study drug or are taking any contraindicated concomitant drugs listed in the package insert. Participants anticipated to require any prohibited concomitant medications during the study period. Participants who are day and night lifestyle reversal. Participants participating in any other clinical studies at the time of informed consent for this study. Pregnant women, nursing mothers, women who are possible pregnant, or women who plan to become pregnant. Other participants who are considered inappropriate for participation in this study in the opinion of the principal investigator or investigator.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trelagliptin 100 mg group<br>Trelagliptin 100 mg once weekly taken orally before breakfast | Drug: Trelagliptin<br>* Trelagliptin 100 mg tablet<br>|
| Experimental: Alogliptin 25 mg group<br>Alogliptin 25 mg once daily taken orally before breakfast | Drug: Alogliptin<br>* Alogliptin 25 mg tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes From Baseline in the Standard Deviation (SD) of 24-hour Blood Glucose Values | Changes in the SD of 24-hour blood glucose values (mg/dL) for each 7-day period between Week 3 and Week 4 (between Day 2 on Week 3 [Day 22] and Day 8 on Week 3 [Day 28]) of the treatment period, calculated from the value at the start of the observation period. | Baseline, up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in AUC for Blood Glucose When Specific Blood Glucose Levels (180 mg/dL) Are Observed During the 3 Hour Time Period After Breakfast, Lunch and Evening Meal | Change from baseline in AUC for blood glucose when specific blood glucose levels (180 mg/dL) were observed during the 3 hour time period after breakfast, lunch and evening meal at each time points was calculated. | Baseline, up to 28 days | 
| Change From Baseline in AUC for Blood Glucose When Specific Blood Glucose Levels (110 mg/dL) Are Observed During the 3 Hour Time Period After Breakfast, Lunch and Evening Meal | Change from baseline in AUC for blood glucose when specific blood glucose levels (110 mg/dL) were observed during the 3 hour time period after breakfast, lunch and evening meal at each time points was calculated. | Baseline, up to 28 days | 
| Change From Baseline in AUC for Blood Glucose When Specific Blood Glucose Levels (140 mg/dL) Are Observed During the 3 Hour Time Period After Breakfast, Lunch and Evening Meal | Change from baseline in AUC for blood glucose when specific blood glucose levels (140 mg/dL) were observed during the 3 hour time period after breakfast, lunch and evening meal at each time points was calculated. | Baseline, up to 28 days | 
| Change From Baseline in AUC for Blood Glucose When Specific Blood Glucose Levels (160 mg/dL) Are Observed During the 3 Hour Time Period After Breakfast, Lunch and Evening Meal | Change from baseline in AUC for blood glucose when specific blood glucose levels (160 mg/dL) were observed during the 3 hour time period after breakfast, lunch and evening meal at each time points was calculated. | Baseline, up to 28 days | 
| Change From Baseline in AUC for Blood Glucose During Periods When Blood Glucose Levels Reached 140 mg/dL (Hyperglycemia) | Change from baseline in AUC for blood glucose during periods when blood glucose levels reached 140 mg/dL at each time points was calculated. | Baseline, up to 28 days | 
| Change From Baseline in AUC for Blood Glucose During Periods When Blood Glucose Levels Reached 160 mg/dL (Hyperglycemia) | Change from baseline in AUC for blood glucose during periods when blood glucose levels reached 160 mg/dL at each time points was calculated. | Baseline, up to 28 days | 
| Change From Baseline in AUC for Blood Glucose During Periods When Blood Glucose Levels Reached 180 mg/dL (Hyperglycemia) | Change from baseline in AUC for blood glucose during periods when blood glucose levels reached 180 mg/dL at each time points was calculated. | Baseline, up to 28 days | 
| Change From Baseline in Time During Periods When Blood Glucose Levels Reached 140 mg/dL (Hyperglycemia) | Change from baseline in cumulative time during periods when blood glucose levels reached 140 mg/dL at each time points was calculated. | Baseline, up to 28 days | 
| Change From Baseline in Time During Periods When Blood Glucose Levels Reached 160 mg/dL (Hyperglycemia) | Change from baseline in cumulative time during periods when blood glucose levels reached 160 mg/dL at each time points was calculated. | Baseline, up to 28 days | 
| Change From Baseline in Time During Periods When Blood Glucose Levels Reached 180 mg/dL (Hyperglycemia) | Change from baseline in cumulative time during periods when blood glucose levels reached 180 mg/dL at each time points was calculated. | Baseline, up to 28 days | 
| Change From Baseline in AUC for Blood Glucose During Periods When Blood Glucose Levels is Less Than 70 mg/dL (Hypoglycemia) | Change from baseline in AUC for blood glucose during periods when blood glucose levels was less than 70 mg/dL at each time points was calculated. | Baseline, up to 28 days | 
| Change From Baseline in Peak Postprandial Glucose Levels During the 3 Hour Time Period After Breakfast, Lunch and Evening Meal | Change from baseline in peak postprandial glucose levels during the 3 hour time period after breakfast, lunch and evening meal at each time points was calculated. | Baseline, up to 28 days | 
| Change From Baseline in Maximum Variation of Blood Glucose Levels Between Before and After Breakfast, Lunch, and Evening Meal | Change from baseline in maximum variation of glucose levels between before and after breakfast, lunch and evening meal at each time points was calculated. | Baseline, up to 28 days | 
| Change From Baseline in Mean Amplitude Glycemic Excursions (MAGE) | Change from baseline in MAGE at each time points was calculated. | Baseline, up to 28 days | 
| Change From Baseline in Mean 24-hour Blood Glucose Levels | Change from baseline in mean 24-hour blood glucose levels at each time points was calculated. | Baseline, up to 28 days | 
| Change From Baseline in Mean Daytime Blood Glucose Levels | Change from baseline in mean daytime blood glucose levels at each time points was calculated. | Baseline, up to 28 days | 
| Change From Baseline in Mean Nocturnal Blood Glucose Levels | Change from baseline in mean nocturnal blood glucose levels at each time points was calculated. | Baseline, up to 28 days | 
| Change From Baseline in AUC for Blood Glucose | Change from baseline in AUC for blood glucose levels at each time points was calculated. | Baseline, up to 28 days | 
| Change From Baseline in AUC for Blood Glucose During Periods When Blood Glucose Levels Reached 110 mg/dL (Hypoglycemia) | Change from baseline in AUC for blood glucose during periods when blood glucose levels reached 110 mg/dL at each time points was calculated. | Baseline, up to 28 days | 
| Standard Deviation (SD) of 24-hour Blood Glucose Values |  | Baseline, up to 28 days | 
| Changes From Baseline in the SD of Daytime Blood Glucose Values | Change from baseline in SD of daytime blood glucose values at each time points was calculated. | Baseline, up to 28 days | 
| Changes From Baseline in the SD of Nocturnal Blood Glucose Values | Change from baseline in SD of nocturnal blood glucose values at each time points was calculated. | Baseline, up to 28 days | 
| Number of Participants Reporting One or More Treatment-emergent Adverse Events |  | Up to 29 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2, Diabetes, Diabetes Mellitus