Study of the QOL Evaluation of Trelagliptin in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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The purpose of this study is to assess the reduction in treatment burden during 12 weeks of trelagliptin administration in patients with type 2 diabetes on diet and exercise therapy only.

Detailed Description
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The purpose of this study is to assess the reduction in treatment burden during 12 weeks of trelagliptin administration in patients with type 2 diabetes on diet and exercise therapy only. Eligible participants will be randomized to either the study drug (trelagliptin) group or the comparative drug (daily DPP-4 inhibitor) group. Treatment burden will be assessed using Diabetes Therapy Related -QOL (DTR-QOL) questionnaire and Diabetes Treatment Satisfaction Questionnaire (DTSQ).

Official Title
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Study of the QOL Evaluation of Trelagliptin in Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Trelagliptin
* Drug: Daily DPP-4 inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants diagnosed as type 2 diabetes. Participants with a stable diet and exercise therapy only for at least 12 weeks prior to the start of the screening period. Participants who require a DPP-4 inhibitor treatment. Participants with Hemoglobin A1c (HbA1c) >=6.5 % and <10.0 % at the start of the screening period. Participants who completed DTR-QOL questionnaire at the start of the screening period. Participants who have received less than 2 types of medication for treatment of comorbidities (such as hypertension or dyslipidemia) at the start of the screening period (any number of daily doses). Participants who, in the opinion of the principal investigator or the investigator, are capable of understanding the content of the clinical study and complying with the study protocol requirements. Participants who can provide the written informed consent prior to the initiation of any study procedures. Participants aged >=20 years at the time of informed consent. Outpatient. Exclusion Criteria: Participants who are receiving any oral anti-diabetic medication for the treatment of type 2 diabetes at the start of the screening period. Participants diagnosed with type 1 diabetes. Participants with severe renal impairment or renal failure (e.g., estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m^2 or on dialysis). Participants with serious heart disease or cerebrovascular disorder, or serious pancreatic, blood, or other disease. Participants with a history of gastrointestinal resection. Participant with a proliferative diabetic retinopathy. Participant with malignancy. Participants with a history of hypersensitivity or allergy to DPP-4 inhibitors. Pregnant, lactating or planning pregnancy during the study period. Participants who may need to add or discontinue concomitant medication or change the dose during the study period. Participants who will require treatment with a prohibited concomitant medication during the study period. Participants participating in other clinical studies. Participants assessed ineligible in the study by the principal investigator or the 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<br>Trelagliptin 100 mg, orally, once weekly for up to 12 weeks. Trelagliptin 50 mg, orally, once weekly for up to 12 weeks in patients with moderate renal impairment. | Drug: Trelagliptin<br>* Trelagliptin 100 mg or 50 mg<br>|
| Active Comparator: Daily DPP-4 inhibitors<br>An inhibitor orally administered at the dosage and administration in the package inserts for each drug, for up to 12 weeks. | Drug: Daily DPP-4 inhibitor<br>* Alogliptin, anagliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin or vildagliptin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Score for All Question Items in the Diabetes Therapy Related -QOL (DTR-QOL) Questionnaire at the End of Study | DTR-QOL Questionnaire is a self-reported instrument assessing impact of diabetes treatment on health-related QOL. It includes 29 items across 4 subscales; Factor 1: Burden on social activities and daily activities (13 questions), Factor 2: Anxiety and dissatisfaction with treatment (8 questions), Factor 3: Hypoglycemia (4 questions) and Factor 4: Treatment satisfaction (4 questions). Each item is scored ranging from 1 to 7. Every score of the questions in Factor 1-3 and the score in Factor 4 converted into reverse (1-7 will be converted to 7-1) will be simply added up, and scores of each factor and the total figure will be subsequently converted from 0 to 100 (the best and worst scores will be equivalent to 100 and 0). Higher scores reflect better QOL and positive changes relative to baseline indicate improvement of QOL. | Baseline (Week 0), up to the end of study (Week 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Score for Each Factor Provided Through the DTR-QOL Questionnaire [Factor 1: Burden on Social Activities and Daily Activities] at Each Assessment Time Point | DTR-QOL Questionnaire is a self-reported instrument assessing impact of diabetes treatment on health-related QOL. It includes 29 items across 4 subscales; Factor 1: Burden on social activities and daily activities (13 questions), Factor 2: Anxiety and dissatisfaction with treatment (8 questions), Factor 3: Hypoglycemia (4 questions) and Factor 4: Treatment satisfaction (4 questions). Each item is scored ranging from 1 to 7. Every score of the questions in Factor 1-3 and the score in Factor 4 converted into reverse (1-7 will be converted to 7-1) will be simply added up, and scores of each factor and the total figure will be subsequently converted from 0 to 100 (the best and worst scores will be equivalent to 100 and 0). Higher scores reflect better QOL and positive changes relative to baseline indicate improvement of QOL. | Baseline (Week 0), up to Week 4, 12, and the end of study (Week 12) | 
| Change From Baseline in Total Score for Each Factor Provided Through the DTR-QOL Questionnaire [Factor 2: Anxiety and Dissatisfaction With Treatments] at Each Assessment Time Point | DTR-QOL Questionnaire is a self-reported instrument assessing impact of diabetes treatment on health-related QOL. It includes 29 items across 4 subscales; Factor 1: Burden on social activities and daily activities (13 questions), Factor 2: Anxiety and dissatisfaction with treatment (8 questions), Factor 3: Hypoglycemia (4 questions) and Factor 4: Treatment satisfaction (4 questions). Each item is scored ranging from 1 to 7. Every score of the questions in Factor 1-3 and the score in Factor 4 converted into reverse (1-7 will be converted to 7-1) will be simply added up, and scores of each factor and the total figure will be subsequently converted from 0 to 100 (the best and worst scores will be equivalent to 100 and 0). Higher scores reflect better QOL and positive changes relative to baseline indicate improvement of QOL. | Baseline (Week 0), up to Week 4, 12, and the end of study (Week 12) | 
| Change From Baseline in Total Score for Each Factor Provided Through the DTR-QOL Questionnaire [Factor 3: Hypoglycemia] at Each Assessment Time Point | DTR-QOL Questionnaire is a self-reported instrument assessing impact of diabetes treatment on health-related QOL. It includes 29 items across 4 subscales; Factor 1: Burden on social activities and daily activities (13 questions), Factor 2: Anxiety and dissatisfaction with treatment (8 questions), Factor 3: Hypoglycemia (4 questions) and Factor 4: Treatment satisfaction (4 questions). Each item is scored ranging from 1 to 7. Every score of the questions in Factor 1-3 and the score in Factor 4 converted into reverse (1-7 will be converted to 7-1) will be simply added up, and scores of each factor and the total figure will be subsequently converted from 0 to 100 (the best and worst scores will be equivalent to 100 and 0). Higher scores reflect better QOL and positive changes relative to baseline indicate improvement of QOL. | Baseline (Week 0), up to Week 4, 12, and the end of study (Week 12) | 
| Change From Baseline in Total Score for Each Factor Provided Through the DTR-QOL Questionnaire [Factor 4: Satisfaction With Treatment] at Each Assessment Time Point | DTR-QOL Questionnaire is a self-reported instrument assessing impact of diabetes treatment on health-related QOL. It includes 29 items across 4 subscales; Factor 1: Burden on social activities and daily activities (13 questions), Factor 2: Anxiety and dissatisfaction with treatment (8 questions), Factor 3: Hypoglycemia (4 questions) and Factor 4: Treatment satisfaction (4 questions). Each item is scored ranging from 1 to 7. Every score of the questions in Factor 1-3 and the score in Factor 4 converted into reverse (1-7 will be converted to 7-1) will be simply added up, and scores of each factor and the total figure will be subsequently converted from 0 to 100 (the best and worst scores will be equivalent to 100 and 0). Higher scores reflect better QOL and positive changes relative to baseline indicate improvement of QOL. | Baseline (Week 0), up to Week 4, 12, and the end of study (Week 12) | 
| Change From Baseline in Total Score for All Question Items in the DTR-QOL Questionnaire at Each Assessment Time Point | DTR-QOL Questionnaire is a self-reported instrument assessing impact of diabetes treatment on health-related QOL. It includes 29 items across 4 subscales; Factor 1: Burden on social activities and daily activities (13 questions), Factor 2: Anxiety and dissatisfaction with treatment (8 questions), Factor 3: Hypoglycemia (4 questions) and Factor 4: Treatment satisfaction (4 questions). Each item is scored ranging from 1 to 7. Every score of the questions in Factor 1-3 and the score in Factor 4 converted into reverse (1-7 will be converted to 7-1) will be simply added up, and scores of each factor and the total figure will be subsequently converted from 0 to 100 (the best and worst scores will be equivalent to 100 and 0). Higher scores reflect better QOL and positive changes relative to baseline indicate improvement of QOL. | Baseline (Week 0), up to Week 4, 12 | 
| Change From Baseline in Total Score for Questions About Treatment Satisfaction in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) at Each Assessment Time Point | The DTSQ is a self-reported instrument consists of 6 questions about treatment satisfaction and 2 questions regarding blood sugar level. Each question answered on a 7-point Likert scale from 0 to 6, based on concern with the diabetes treatment and experiences in the past few weeks. Higher total score for questions about treatment satisfaction indicate greater satisfaction with treatment and experiences. | Baseline (Week 0), up to Week 4, 12 and the end of study (Week 12) | 
| Change From Baseline in Total Score for All Question Items in the DTR-QOL Questionnaire at the End of Study Stratified by the Use of Medication for Treatment of Comorbidities at Baseline | DTR-QOL Questionnaire is a self-reported instrument assessing impact of diabetes treatment on health-related QOL. It includes 29 items across 4 subscales; Factor 1: Burden on social activities and daily activities (13 questions), Factor 2: Anxiety and dissatisfaction with treatment (8 questions), Factor 3: Hypoglycemia (4 questions) and Factor 4: Treatment satisfaction (4 questions). Each item is scored ranging from 1 to 7. Every score of the questions in Factor 1-3 and the score in Factor 4 converted into reverse (1-7 will be converted to 7-1) will be simply added up, and scores of each factor and the total figure will be subsequently converted from 0 to 100 (the best and worst scores will be equivalent to 100 and 0). Higher scores reflect better QOL and positive changes relative to baseline indicate improvement of QOL. Reported data was the score stratified by the use of medication for treatment of comorbidities at baseline (Used/ Not used). | Baseline (Week 0), up to the end of study (Week 12) | 
| Change From Baseline in Total Score for Questions About Treatment Satisfaction in the DTSQ at the End of Study Stratified by the Use of Medication for Treatment of Comorbidities at Baseline | The DTSQ is a self-reported instrument consists of 6 questions about treatment satisfaction and 2 questions regarding blood sugar level. Each question answered on a 7-point Likert scale from 0 to 6, based on concern with the diabetes treatment and experiences in the past few weeks. Higher total score for questions about treatment satisfaction indicate greater satisfaction with treatment and experiences. Reported data was the score stratified by the use of medication for treatment of comorbidities at baseline (Used/ Not used). | Baseline (Week 0), up to the end of study (Week 12) | 
| Change From Baseline in Total Score for All Question Items in the DTR-QOL Questionnaire at the End of Study Stratified by the Number of Daily Doses of Medication for Treatment of Comorbidities (<2 Times or ≥2 Times) at Baseline | DTR-QOL Questionnaire is a self-reported instrument assessing impact of diabetes treatment on health-related QOL. It includes 29 items across 4 subscales; Factor 1: Burden on social activities and daily activities (13 questions), Factor 2: Anxiety and dissatisfaction with treatment (8 questions), Factor 3: Hypoglycemia (4 questions) and Factor 4: Treatment satisfaction (4 questions). Each item is scored ranging from 1 to 7. Every score of the questions in Factor 1-3 and the score in Factor 4 converted into reverse (1-7 will be converted to 7-1) will be simply added up, and scores of each factor and the total figure will be subsequently converted from 0 to 100 (the best and worst scores will be equivalent to 100 and 0). Higher scores reflect better QOL and positive changes relative to baseline indicate improvement of QOL. | Baseline (Week 0), up to the end of study (Week 12) | 
| Change From Baseline in Total Score for Questions About Treatment Satisfaction in the DTSQ at the End of Study Stratified by the Number of Daily Doses of Medication for Treatment of Comorbidities (<2 Times or ≥2 Times) at Baseline | The DTSQ is a self-reported instrument consists of 6 questions about treatment satisfaction and 2 questions regarding blood sugar level. Each question answered on a 7-point Likert scale from 0 to 6, based on concern with the diabetes treatment and experiences in the past few weeks. Higher total score for questions about treatment satisfaction indicate greater satisfaction with treatment and experiences. | Baseline (Week 0), up to the end of study (Week 12) | 
| Change From Baseline in Total Score for All Question Items in the DTR-QOL Questionnaire at the End of Study Stratified by the Total Number of Daily Tablets of Medication for Treatment of Comorbidities (<2 Tablets or ≥2 Tablets) at Baseline | DTR-QOL Questionnaire is a self-reported instrument assessing impact of diabetes treatment on health-related QOL. It includes 29 items across 4 subscales; Factor 1: Burden on social activities and daily activities (13 questions), Factor 2: Anxiety and dissatisfaction with treatment (8 questions), Factor 3: Hypoglycemia (4 questions) and Factor 4: Treatment satisfaction (4 questions). Each item is scored ranging from 1 to 7. Every score of the questions in Factor 1-3 and the score in Factor 4 converted into reverse (1-7 will be converted to 7-1) will be simply added up, and scores of each factor and the total figure will be subsequently converted from 0 to 100 (the best and worst scores will be equivalent to 100 and 0). Higher scores reflect better QOL and positive changes relative to baseline indicate improvement of QOL. | Baseline (Week 0), up to the end of study (Week 12) | 
| Change From Baseline in Total Score for Questions About Treatment Satisfaction in the DTSQ at the End of Study Stratified by the Total Number of Daily Tablets of Medication for Treatment of Comorbidities (<2 Tablets or ≥2 Tablets) at Baseline | The DTSQ is a self-reported instrument consists of 6 questions about treatment satisfaction and 2 questions regarding blood sugar level. Each question answered on a 7-point Likert scale from 0 to 6, based on concern with the diabetes treatment and experiences in the past few weeks. Higher total score for questions about treatment satisfaction indicate greater satisfaction with treatment and experiences. | Baseline (Week 0), up to the end of study (Week 12) | 
| Change From Baseline in Total Score for All Question Items in the DTR-QOL Questionnaire at the End of Study Stratified by the Number of Doses of the Study Drug or Comparative Drug (Once Weekly, Once Daily or Twice Daily) at Baseline | DTR-QOL Questionnaire is a self-reported instrument assessing impact of diabetes treatment on health-related QOL. It includes 29 items across 4 subscales; Factor 1: Burden on social activities and daily activities (13 questions), Factor 2: Anxiety and dissatisfaction with treatment (8 questions), Factor 3: Hypoglycemia (4 questions) and Factor 4: Treatment satisfaction (4 questions). Each item is scored ranging from 1 to 7. Every score of the questions in Factor 1-3 and the score in Factor 4 converted into reverse (1-7 will be converted to 7-1) will be simply added up, and scores of each factor and the total figure will be subsequently converted from 0 to 100 (the best and worst scores will be equivalent to 100 and 0). Higher scores reflect better QOL and positive changes relative to baseline indicate improvement of QOL. | Baseline (Week 0), up to the end of study (Week 12) | 
| Change From Baseline in Total Score for Questions About Treatment Satisfaction in the DTSQ at the End of Study Stratified by the Number of Doses of the Study Drug or Comparative Drug (Once Weekly, Once Daily or Twice Daily) at Baseline | The DTSQ is a self-reported instrument consists of 6 questions about treatment satisfaction and 2 questions regarding blood sugar level. Each question answered on a 7-point Likert scale from 0 to 6, based on concern with the diabetes treatment and experiences in the past few weeks. Higher total score for questions about treatment satisfaction indicate greater satisfaction with treatment and experiences. | Baseline (Week 0), up to the end of study (Week 12) | 
| Change From Baseline in Score Per Question in the DTR-QOL Questionnaire at the End of Study | DTR-QOL Questionnaire is a self-reported instrument assessing impact of diabetes treatment on health-related QOL. It includes 29 items across 4 subscales; Factor 1: Burden on social activities and daily activities (13 questions), Factor 2: Anxiety and dissatisfaction with treatment (8 questions), Factor 3: Hypoglycemia (4 questions) and Factor 4: Treatment satisfaction (4 questions). Each item is scored ranging from 1 to 7. Every score of the questions in Factor 1-3 and the score in Factor 4 converted into reverse (1-7 will be converted to 7-1) will be simply added up, and scores of each factor and the total figure will be subsequently converted from 0 to 100 (the best and worst scores will be equivalent to 100 and 0). Higher scores reflect better QOL and positive changes relative to baseline indicate improvement of QOL. | Baseline (Week 0), up to end of study (Week 12) | 
| Change From Baseline in Score Per Question in the the DTSQ at the End of Study | The DTSQ is a self-reported instrument consists of 6 questions about treatment satisfaction and 2 questions regarding blood sugar level. Each question answered on a 7-point Likert scale from 0 to 6, based on concern with the diabetes treatment and experiences in the past few weeks. Higher total score for questions about treatment satisfaction indicate greater satisfaction with treatment and experiences. | Baseline (Week 0), up to end of study (Week 12) | 
| Number of Participants Reporting One or More Treatment-emergent Adverse Events | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. | Up to 12 weeks | 
| Number of Participants Reporting One or More Hypoglycemia |  | Up to 12 weeks | 
| Duration of Hospitalization for Type 2 Diabetes (Excluding Educational Hospitalization Without Worsening of Diabetes) | The investigators checked any hospitalization of study participants for type 2 diabetes after the first administration of the study drug or comparative drug (excluding educational hospitalization without worsening of diabetes). | Up to 12 weeks | 
| Number of Participants With Hospitalization for Type 2 Diabetes (Excluding Educational Hospitalization Without Worsening of Diabetes) |  | Up to 12 weeks |