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

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

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).

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Trelagliptin; Drug: Alogliptin

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Ibaragi
    • Naka-city, Ibaragi, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trelagliptin 100 mg group; Trelagliptin 100 mg once weekly taken orally before breakfast	Drug: Trelagliptin; Trelagliptin 100 mg tablet
Experimental: Alogliptin 25 mg group; Alogliptin 25 mg once daily taken orally before breakfast	Drug: Alogliptin; Alogliptin 25 mg tablet

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

General Publications

• Nishimura R, Osonoi T, Koike Y, Miyata K, Shimasaki Y. A Randomized Pilot Study of the Effect of Trelagliptin and Alogliptin on Glycemic Variability in Patients with Type 2 Diabetes. Adv Ther. 2019 Nov;36(11):3096-3109. doi: 10.1007/s12325-019-01097-z. Epub 2019 Sep 27.

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2016
• Primary Completion (Actual): April 27, 2017
• Study Completion (Actual): April 27, 2017

Study Registration Dates

• First Submitted: May 11, 2016
• First Submitted That Met QC Criteria: May 11, 2016
• First Posted (Estimated): May 12, 2016

Study Record Updates

• Last Update Posted (Estimated): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 7, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Type 2, Diabetes, Diabetes Mellitus
• 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; Dipeptidyl-Peptidase IV Inhibitors; Alogliptin
• Other Study ID Numbers: Trelagliptin-4001; U1111-1182-4062 (Other Identifier: UTN); JapicCTI-163250 (Registry Identifier: JapicCTI)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No