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

Phase 4
Completed
Conditions
Type 2 Diabetes Mellitus
Interventions
Registration Number
NCT02771093
Lead Sponsor
Takeda
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
27
Inclusion Criteria
  1. 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.
  2. Participants who are able to sign and date the informed consent form and information sheet prior to the start of study procedures.
  3. Participants diagnosed with type 2 diabetes mellitus.
  4. 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).
  5. 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.
  6. Participants receiving stable dietetic therapy and exercise therapy (if performed) for ≥ 4 weeks before the start of the observation period.
  7. 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.
  8. Men or women aged 20 years or older at the time of informed consent.
Exclusion Criteria
  1. Participants who received anti-diabetic medications within 4 weeks prior to the start of the observation period.
  2. 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.
  3. 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]).
  4. 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]).
  5. Participants with severe heart disease, cerebrovascular disorder, or severe pancreatic, hematologic or other diseases.
  6. Participants with a history of gastric or small intestinal resection.
  7. Participants with proliferative diabetic retinopathy.
  8. 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).
  9. Participants with a history of hypersensitivity or allergy to DPP-4 inhibitors.
  10. Participants who experience an allergic reaction to metal during CGM at the start of the observation period (Day -2).
  11. Participants with any malignant tumors.
  12. Habitual drinkers whose average daily alcohol consumption is > 100 mL.
  13. Participants who have any contraindications for the study drug or are taking any contraindicated concomitant drugs listed in the package insert.
  14. Participants anticipated to require any prohibited concomitant medications during the study period.
  15. Participants who are day and night lifestyle reversal.
  16. Participants participating in any other clinical studies at the time of informed consent for this study.
  17. Pregnant women, nursing mothers, women who are possible pregnant, or women who plan to become pregnant.
  18. Other participants who are considered inappropriate for participation in this study in the opinion of the principal investigator or investigator.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Trelagliptin 100 mg groupTrelagliptinTrelagliptin 100 mg once weekly taken orally before breakfast
Alogliptin 25 mg groupAlogliptinAlogliptin 25 mg once daily taken orally before breakfast
Primary Outcome Measures
NameTimeMethod
Changes From Baseline in the Standard Deviation (SD) of 24-hour Blood Glucose ValuesBaseline, up to 28 days

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.

Secondary Outcome Measures
NameTimeMethod
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 MealBaseline, up to 28 days

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.

Change From Baseline in AUC for Blood Glucose During Periods When Blood Glucose Levels Reached 110 mg/dL (Hypoglycemia)Baseline, up to 28 days

Change from baseline in AUC for blood glucose during periods when blood glucose levels reached 110 mg/dL at each time points was calculated.

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 MealBaseline, up to 28 days

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.

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 MealBaseline, up to 28 days

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.

Change From Baseline in AUC for Blood Glucose During Periods When Blood Glucose Levels Reached 180 mg/dL (Hyperglycemia)Baseline, up to 28 days

Change from baseline in AUC for blood glucose during periods when blood glucose levels reached 180 mg/dL at each time points was calculated.

Change From Baseline in Time During Periods When Blood Glucose Levels Reached 140 mg/dL (Hyperglycemia)Baseline, up to 28 days

Change from baseline in cumulative time during periods when blood glucose levels reached 140 mg/dL at each time points was calculated.

Change From Baseline in Time During Periods When Blood Glucose Levels Reached 160 mg/dL (Hyperglycemia)Baseline, up to 28 days

Change from baseline in cumulative time during periods when blood glucose levels reached 160 mg/dL at each time points was calculated.

Change From Baseline in Time During Periods When Blood Glucose Levels Reached 180 mg/dL (Hyperglycemia)Baseline, up to 28 days

Change from baseline in cumulative time during periods when blood glucose levels reached 180 mg/dL at each time points was calculated.

Change From Baseline in AUC for Blood Glucose During Periods When Blood Glucose Levels is Less Than 70 mg/dL (Hypoglycemia)Baseline, up to 28 days

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.

Change From Baseline in Maximum Variation of Blood Glucose Levels Between Before and After Breakfast, Lunch, and Evening MealBaseline, up to 28 days

Change from baseline in maximum variation of glucose levels between before and after breakfast, lunch and evening meal at each time points was calculated.

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 MealBaseline, up to 28 days

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.

Change From Baseline in AUC for Blood Glucose During Periods When Blood Glucose Levels Reached 140 mg/dL (Hyperglycemia)Baseline, up to 28 days

Change from baseline in AUC for blood glucose during periods when blood glucose levels reached 140 mg/dL at each time points was calculated.

Change From Baseline in AUC for Blood Glucose During Periods When Blood Glucose Levels Reached 160 mg/dL (Hyperglycemia)Baseline, up to 28 days

Change from baseline in AUC for blood glucose during periods when blood glucose levels reached 160 mg/dL at each time points was calculated.

Change From Baseline in Mean 24-hour Blood Glucose LevelsBaseline, up to 28 days

Change from baseline in mean 24-hour blood glucose levels at each time points was calculated.

Change From Baseline in Mean Nocturnal Blood Glucose LevelsBaseline, up to 28 days

Change from baseline in mean nocturnal blood glucose levels at each time points was calculated.

Change From Baseline in Peak Postprandial Glucose Levels During the 3 Hour Time Period After Breakfast, Lunch and Evening MealBaseline, up to 28 days

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.

Change From Baseline in Mean Amplitude Glycemic Excursions (MAGE)Baseline, up to 28 days

Change from baseline in MAGE at each time points was calculated.

Change From Baseline in Mean Daytime Blood Glucose LevelsBaseline, up to 28 days

Change from baseline in mean daytime blood glucose levels at each time points was calculated.

Change From Baseline in AUC for Blood GlucoseBaseline, up to 28 days

Change from baseline in AUC for blood glucose levels at each time points was calculated.

Standard Deviation (SD) of 24-hour Blood Glucose ValuesBaseline, up to 28 days
Changes From Baseline in the SD of Daytime Blood Glucose ValuesBaseline, up to 28 days

Change from baseline in SD of daytime blood glucose values at each time points was calculated.

Changes From Baseline in the SD of Nocturnal Blood Glucose ValuesBaseline, up to 28 days

Change from baseline in SD of nocturnal blood glucose values at each time points was calculated.

Number of Participants Reporting One or More Treatment-emergent Adverse EventsUp to 29 days
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