Effect of DapagliFLOzin on Quality of Life in Patients With Type 2 Diabetes in a Real Clinical PrActice

Study Overview
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Brief Summary
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This is a multicenter, randomised, open-label, crossover, 2-period comparative phase IV study. The primary objective is to compare the effect of dapagliflozin 10 mg once daily in combination with metformin at a daily dose of ≤1,500 mg vs. metformin monotherapy with dose titrated up to 2,500 mg/day on the overall quality of life, obesity-specific quality of life and treatment satisfaction in patients with type 2 diabetes.

Detailed Description
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The study will comprise the following phases: Screening, Treatment Period 1 and Treatment Period 2. After screening examinations and assessments, all patients enrolled will be randomly assigned in equal proportion (1:1) to either study arm: Arm 1: Patients will take dapagliflozin 10 mg in combination with metformin ≤ 1,500 mg (daily dose) for 24 weeks during Treatment Period 1 Patients will be on metformin monotherapy with dose titrated up to 2,500 mg/day for further 24 weeks during Treatment Period 2 Arm 2 (the same treatment phases in reverse order): Patients will be on metformin monotherapy with dose titrated up to 2,500 mg/day for 24 weeks during Treatment Period 1 Patients will take dapagliflozin 10 mg in combination with metformin ≤ 1,500 mg (daily dose) for further 24 weeks during Treatment Period 2 Following the randomisation procedure, patients will receive investigational products at each visit as scheduled by Treatment Period 1. After the Randomisation Visit (Visit 2), the patient should attend the study centre for Visits 3, 4, and 5 (Day 28, Day 86, and Day 168, respectively) for efficacy and safety assessments. At Visit 5 (Day 168), the patient will receive investigational products as required by Treatment Period 2. Further Visits 6, 7 and 8 will be scheduled on Day 196, Day 252, Day 336, respectively.

Official Title
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A Multicentre Randomised Open-Label Crossover 2-Period 2 Treatment Clinical Trial to Evaluate Effect of Dapagliflozin 10 mg Once Daily on the Quality of Life in Patients With Type 2 Diabetes

Conditions
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Diabetes Mellitus Type 2

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For inclusion in the study patients should fulfil ALL the criteria listed below: A voluntary informed consent form for participation in the study signed by the patient prior to any study-specific procedures Male and female patients of 18-74 years of age Diagnosed type 2 diabetes Therapy with metformin at a stable dose ≤1,500 mg/day for at least 8 weeks before enrolment HbA1c >7.0% and ≤10% at the Screening Visit C-peptide ≥1.0 ng/ml at the Screening Visit Body mass index ≤45.0 kg/m² at the Screening Visit For women of childbearing potential - use of reliable birth control methods Ability to complete study-specific procedures Ability to complete questionnaires Exclusion Criteria: Type 1 diabetes Diabetic ketoacidosis at Screening AST and/or ALT > 3 × upper limit of normal at Screening Total serum bilirubin > 34.19 μmol/l at Screening Decompensated diabetes mellitus (HbA1c >10% at Screening) Patients with moderate to severe renal impairment (CrCl <60 ml/min or <60 ml/min/1.73 m2 at Screening) or terminal renal insufficiency Severe concomitant diseases or severe cardiovascular, renal, hepatic, hematologic, endocrine, mental or rheumatic pathology Malignancy within 5 years before enrolment Acute (including viral and infectious) diseases within 1 month before the Screening Visit. Development of severe acute diseases during the study which significantly affect the benefit/risk ratio for the subject or affecting study efficacy/safety assessment criteria History of acute myocardial infarction or stroke within 6 months before the Screening Visit or during the study. Heart failure (NYHA III-IV) Treatment with drugs affecting glucose homeostasis (e.g., systemic glucocorticosteroids) within 3 months before to the Screening Visit. For women of childbearing potential - a positive pregnancy test or the patient is breast-feeding or planning pregnancy during the study History of Hepatitis B and C or HIV Individual hypersensitivity to any component of the investigational product (dapagliflozin) Treatment with sodium-dependent glucose cotransporter inhibitors (SGLT2) has been administered within 3 months prior to enrolment or is planned during the study. Loop diuretics have been administered for 3 months before the Screening Visit or are planned during the study. Hereditary lactose intolerance, lactase deficiency and glucose-galactose malabsorption The patient is unable to follow study procedures and attend the study centre for scheduled study visits or is going to relocate within the protocol-specific timelines The patient is a subject of other studies within 3 months before enrolment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 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: Arm 1<br>Arm 1 - therapy with dapagliflozin 10 mg once daily in combination with metformin ≤ 1,500 mg (daily dose) for 24 weeks (Treatment Regimen 1) followed by metformin monotherapy with dose titrated up to 2,500 mg/day for further 24 weeks (Treatment Regimen 2) | Drug: Dapagliflozin<br>* Dapagliflozin, 10 mg<br>* Other names: Forxiga;Drug: Metformin<br>* Metformin, up to 2500 mg<br>* Other names: Glucophage;|
| Active Comparator: Arm 2<br>Arm 2 - metformin monotherapy with dose titrated up to 2,500 mg/day for 24 weeks (Treatment Regimen 2) followed by therapy with dapagliflozin 10 mg once daily in combination with metformin ≤ 1,500 mg (daily dose) for further 24 weeks (Treatment Regimen 1) | Drug: Dapagliflozin<br>* Dapagliflozin, 10 mg<br>* Other names: Forxiga;Drug: Metformin<br>* Metformin, up to 2500 mg<br>* Other names: Glucophage;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite endpoint including quality of life score | Change in the overall quality of life, obesity-specific quality of life and treatment satisfaction in the course of the therapy by the end of each 24-week treatment period compared to the quality of life, obesity-specific quality of life and treatment satisfaction at baseline. | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c level | Change in HbA1c level will be assessed as mean change in the course of the treatment compared to baseline. | 48 weeks | 
| Change in body weight | Change in body weight will be assessed as mean change in body weight, mean percentage change in body weight and mean change in body mass index compared to baseline and as proportion of patients with body weight decreased by ≥5% during the treatment phase. | 48 weeks | 
| Change in waist circumference | Change in waist circumference will be assessed as mean change and mean percentage change in waist circumference during the treatment phase compared to baseline. | 48 weeks | 
| Change in fasting plasma glucose | Change in fasting plasma glucose will be assessed as mean change in fasting plasma glucose during the treatment phase compared to baseline. | 48 weeks | 
| Proportion of patients | Proportion of patients who achieved therapeutic glycaemic response (HbA1c ≤7%). | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus type 2, dapagliflozin, quality of life