SWITCH: Comparison of Two Treatment Regimens in Patients With Type 2 Diabetes After Short-term Intensive Insulin Therapy

Sponsor

Sanofi (Industry)

Overall Status

Completed

CT.gov ID

NCT03359837

Collaborator

(none)

384

Enrollment

Location

Arms

29.3

Actual Duration (Months)

13.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary Objective:

To test the hypothesis that basal insulin based treatment (G+) is noninferior to twice-daily premixed insulin (PM-2) in term of hemoglobin A1c (glycosylated hemoglobin, HbA1c) reduction from baseline to end of study. The test for superiority can be done if noninferiority is achieved.

Secondary Objectives:

To assess efficacy in terms of percentage of patients achieving HbA1c <7% and HbA1c <7% without hypoglycemia.
To assess efficacy in terms of percentage of patients achieving fasting plasma glucose (FPG) <7 mmol/L and FPG <7 mmol/L without hypoglycemia.
To assess safety in term of occurrence of moderate/severe hypoglycemia.
To assess daily blood glucose (BG) variation.
To assess patient satisfaction.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: INSULIN GLARGINE (HOE901) Drug: Insulin Glulisine Drug: Biphasic insulin aspart 30 Drug: Repaglinide Drug: Acarbose Drug: Metformin	Phase 4

Detailed Description

The duration of study is approximately 21 months. Each patient will be followed for approximately 27 weeks from screening visit to end-of-study

Study Design

Study Type:

Interventional

Actual Enrollment :

384 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A 26-Week, Multi-Center, Open-label, Randomized, Parallel-group Study to Evaluate the Efficacy and Safety of Two Treatment Regimens in Patients With Type 2 Diabetes After Short-Term Intensive Insulin Therapy: Basal Insulin Based Treatment (With Prandial OADs Combination) Versus Twice-daily Premixed Insulin

Actual Study Start Date :

Jan 20, 2018

Actual Primary Completion Date :

Jun 29, 2020

Actual Study Completion Date :

Jun 29, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Glargine based therapy Once daily glargine plus prandial oral anti-hyperglycemic drugs	Drug: INSULIN GLARGINE (HOE901) Pharmaceutical form: solution for injection Route of administration: subcutaneous injection Other Names: Lantus Drug: Insulin Glulisine Pharmaceutical form: solution for injection Route of administration: subcutaneous injection Other Names: Apidra Drug: Repaglinide Pharmaceutical form: tablet Route of administration: oral administration Other Names: NovoNorm Drug: Acarbose Pharmaceutical form: tablet Route of administration: oral administration Other Names: Glucobay
Active Comparator: Premixed insulin Twice daily premixed insulin	Drug: Biphasic insulin aspart 30 Pharmaceutical form: solution for injection Route of administration: subcutaneous injection Other Names: Novolog Mix70/30 Drug: Metformin Pharmaceutical form: tablet or capsule Route of administration: oral administration

Arm

Intervention/Treatment

Experimental: Glargine based therapy

Once daily glargine plus prandial oral anti-hyperglycemic drugs

Drug: INSULIN GLARGINE (HOE901)

Pharmaceutical form: solution for injection Route of administration: subcutaneous injection

Other Names:

Lantus

Drug: Insulin Glulisine

Pharmaceutical form: solution for injection Route of administration: subcutaneous injection

Other Names:

Apidra

Drug: Repaglinide

Pharmaceutical form: tablet Route of administration: oral administration

Other Names:

NovoNorm

Drug: Acarbose

Pharmaceutical form: tablet Route of administration: oral administration

Other Names:

Glucobay

Active Comparator: Premixed insulin

Twice daily premixed insulin

Drug: Biphasic insulin aspart 30

Pharmaceutical form: solution for injection Route of administration: subcutaneous injection

Other Names:

Novolog Mix70/30

Drug: Metformin

Pharmaceutical form: tablet or capsule Route of administration: oral administration

Outcome Measures

Primary Outcome Measures

Change in hemoglobin A1c (HbA1c) [Baseline to Week 24]
Change in HbA1c from baseline to week 24

Secondary Outcome Measures

Patients with fasting plasma glucose (FPG) <6.1 mmol/L [At Week 12 and Week 24]
Percentage of patients with FPG <6.1 mmol/L at week 12 and week 24
Patients with FPG <6.1 mmol/L without hypoglycemia [At Week 12 and Week 24]
Percentage of patients with FPG <6.1 mmol/L without hypoglycemia at week 12 and week 24
Patients with FPG <7 mmol/L [At Week 12 and Week 24]
Percentage of patients with FPG <7 mmol/L at week 12 and week 2
Patients with FPG <7 mmol/L without hypoglycemia [At Week 12 and Week 24]
Percentage of patients with FPG <7 mmol/L without hypoglycemia at week 12 and week 24
Patients with HbA1c <7% [At Week 12 and Week 24]
Percentage of patients with HbA1c <7% at week 12 and week 24
Patients with HbA1c <7% without hypoglycemia [At Week 12 and Week 24]
Percentage of patients with HbA1c <7% without hypoglycemia at week 12 and week 24
Hypoglycemic events [Baseline to Week 24]
Incidence of hypoglycemia during treatment period
Change in FPG [Baseline to Week 24]
Change in FPG from baseline to week 24
Change in body weight [Baseline to Week 24]
Change in body weight from baseline to week 24
Insulin dose [At Week 24]
Total daily insulin dose at week 24
Daily BG variation at week 24 [At Week 24]
Daily blood glucose (BG) variation at week 24
European quality of life - 5 dimensions (EQ-5D) [Baseline to Week 24]
Change in quality of life scores from baseline to week 24 on 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is measured at 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problem.
Subgroup analysis [At week 24]
Subgroup analysis of control rate of HbA1c <7% according to duration of diabetes, oral anti-hyperglycemic drug(OAD) treatment and HbA1c at screening, FPG, post prandial glucose(PPG) excursion and C peptide at the beginning of run-in period, insulin dose at end of run-in period

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria :

Patients with age between 18 and 70 years.
Hemoglobin A1c>7.5%, and ≤11%.
Fasting plasma glucose >7 mmol/L.
Fasting C peptide >1 ng/mL.
Type 2 diabetes (T2DM) patients with diabetes diagnosis between 2 and 10 years (World Health Organization 1999 T2DM diagnose criteria).
Continuous treatment with stable doses of metformin (≥1 g/day) and 1 oral antihyperglycemic drug (at least half maximum dose) for more than 3 months prior to screening.
Body mass index ≥21 kg/m2, and <40 kg/m2.

Exclusion criteria:

More than 7 consecutive days of insulin treatment within the 12 months except for acute disease or surgery.
Diabetes other than T2DM (e.g. type 1 diabetes, diabetes secondary to pancreatic disorders, drug or chemical agent intake).
History of hypoglycemia unawareness or recurrent hypoglycemia or severe hypoglycemia within the past 12 months.
History of sensitivity to the study drugs or to drugs with a similar chemical structure.
Pregnancy or planned pregnancy or current lactation (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraception method).
Acute diabetic complications (diabetic ketoacidosis, lactic acidosis, hyperosmolar nonketotic diabetic coma) within the past 12 months.
Significant diabetic complications and serious disease, e.g., symptomatic autonomic neuropathy, gastroparesis, unstable angina or active proliferative retinopathy.
Acute infections which may affect BG control within the past 4 weeks.
Active liver disease, alanine transaminase (ALT) and/or aspartate aminotransferase (AST) greater than two times the upper limit of the reference range at screening.
Impaired renal function, defined as but not limited to, serum creatinine levels ≥1.5 mg/dL (132 μmol/L) for males and ≥1.4 mg/dL (123 μmol/L) for females or presence of macroproteinuria (>2 g/day).