A Phase 3, Double-blind, Randomized Study to Assess the Efficacy and Safety of Ipragliflozin in Combination With Metformin Compared to Metformin Plus Placebo in Subjects in Russia With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin
Overview
- Phase
- Phase 3
- Intervention
- Metformin
- Conditions
- Type 2 Diabetes Mellitus
- Sponsor
- Astellas Pharma Europe B.V.
- Enrollment
- 268
- Locations
- 14
- Primary Endpoint
- Change from baseline in HbA1c with ipragliflozin once daily added on to metformin compared to placebo added on to metformin
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The main purpose of this study is to evaluate the efficacy in reducing glycated hemoglobin of ipragliflozin in combination with metformin compared with metformin plus placebo in subjects with type 2 diabetes mellitus who have inadequate glycemic control on metformin.
Detailed Description
This is a phase 3, double-blind, randomized study to assess the efficacy and safety of ipragliflozin in combination with metformin compared to metformin plus placebo in subjects in Russia with type 2 diabetes mellitus who have inadequate glycemic control on metformin. Subjects will enter a 10-day (± 3 days) screening period, followed by a 2-week single-blind placebo run-in period, followed by a 24-week randomized double-blind treatment period and a 4-week follow-up period
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject has been diagnosed with type 2 diabetes mellitus at least 12 weeks before visit
- •Subject has been on a stable dose and a daily dose regimen of metformin ≥ 1500 mg for at least 12 weeks prior to visit
- •Subject has HbA1c ≥ 7.5% and ≤ 11.0% at visit
- •Subject has been on a stable diet and exercise program for at least 12 weeks prior to visit 1 and is willing to maintain this program for the duration of the treatment period.
- •Subject has a body mass index (BMI) of 20 to 45 kg/m2, inclusive, at visit
- •Subjects are allowed to continue taking their medication for concomitant diseases (including over-the-counter products), provided they have been on a stable dose for a minimum of 30 days prior to visit
- •Female subjects must either:
- •Be of non-childbearing potential:
- •postmenopausal (defined as at least 1 year without any menses) prior to screening, or
- •documented as surgically sterile
Exclusion Criteria
- •Subject has type 1 diabetes mellitus.
- •Subject has received any medication for glycemic control, with the exception of metformin, (e.g., oral antidiabetic drugs, insulin, etc.) within 12 weeks prior to visit
- •Subject is currently receiving an excluded medication or has received insulin within 12 weeks prior to visit 1 or during the screening period.
- •Subject has a history of stroke, unstable angina, myocardial infarction, any vascular intervention or heart failure (New York Heart Association Class III-IV;) within 12 weeks prior to visit
- •Subject has had a malignancy in the last 5 years, except for adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
- •Subject has a history of diabetic coma or precoma.
- •Subject has a history of ketoacidosis or lactic acidosis.
- •History of drinking more than 21 units of alcohol per week (1 unit = 10 g pure alcohol = 250 mL of beer \[5%\] or 35 mL of spirits \[35%\] or 100 mL of wine \[12%\]) (\> 14 units of alcohol for female subjects) or history of drugs abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, and opiates) within 3 months prior to visit
- •Subject is known to have hepatitis or be a carrier of hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody or is known to be positive for human immunodeficiency virus (HIV)-1 and/or HIV-
- •Subject has a severe infection, has serious trauma, or is a perioperative subject.
Arms & Interventions
Metformin and placebo
Participants will receive daily dosage of Metformin and Placebo as single tablets.
Intervention: Metformin
Metformin and placebo
Participants will receive daily dosage of Metformin and Placebo as single tablets.
Intervention: Placebo
Metformin and Ipragliflozin
Participants will receive daily dosage of Metformin and Ipragliflozin (2 dose strengths) as single tablets.
Intervention: Ipragliflozin L-proline
Metformin and Ipragliflozin
Participants will receive daily dosage of Metformin and Ipragliflozin (2 dose strengths) as single tablets.
Intervention: Metformin
Metformin, placebo and Ipragliflozin
Participants will receive daily dosage of Metformin, placebo and Ipragliflozin (1 dose strength) as single tablets.
Intervention: Ipragliflozin L-proline
Metformin, placebo and Ipragliflozin
Participants will receive daily dosage of Metformin, placebo and Ipragliflozin (1 dose strength) as single tablets.
Intervention: Metformin
Metformin, placebo and Ipragliflozin
Participants will receive daily dosage of Metformin, placebo and Ipragliflozin (1 dose strength) as single tablets.
Intervention: Placebo
Outcomes
Primary Outcomes
Change from baseline in HbA1c with ipragliflozin once daily added on to metformin compared to placebo added on to metformin
Time Frame: Baseline and 12 weeks
Glycated hemoglobin (HbA1c)
Secondary Outcomes
- Number of patients with AEs of special interest(Up to 24 weeks)
- Change from baseline in PROs as measured by European Quality of Life 5 Dimensions 5 Levels [EQ-5D-5L] questionnaire(Baseline, 12 weeks and 24 weeks)
- Change in body weight in each treatment group(Baseline, 12 weeks and 24 weeks)
- Number of patients with AEs(Up to 24 weeks)
- Change from baseline in PROs as measured by Audit of Diabetes Dependent Quality of Life [ADDQoL-19] questionnaire(Baseline, 12 weeks and 24 weeks)
- Change from baseline in PROs as measured by Work Productivity and Activity Impairment: General Health [WPAI:GH] questionnaire(Baseline, 12 weeks and 24 weeks)
- Change from baseline in PROs as measured by Diabetes Medication Satisfaction [Diab-MedSat] questionnaire(Baseline, 12 weeks and 24 weeks)
- Percentage of patients with AEs(Up to 24 weeks)
- Change from baseline in HbA1c in each treatment group(Baseline and 24 weeks)
- Change from baseline in FPG in each treatment group(Baseline, 12 weeks and 24 weeks)
- Change in blood pressure in each treatment group(Baseline, 12 weeks and 24 weeks)
- Percentage of patients reaching a treatment goal in HbA1c of < 7.0% in each treatment group(Up to 24 weeks)
- Number of patients reaching a treatment goal in HbA1c of < 7.0% in each treatment group(Up to 24 weeks)
- Percentage of patients with AEs of special interest(Up to 24 weeks)