Type 2 Diabetes Mellitus
Conditions
Brief summary
Primary Objective: To demonstrate that the simple daily titration algorithm is non-inferior to the weekly titration algorithm according to Canadian labeling. Secondary Objective: To gain additional information on the efficacy and safety of using a simple patient-titration protocol for administration of insulin glargine/lixisenatide fixed-ratio combination (iGlarLixi).
Detailed description
The maximum duration of study per patient is approximately 29 weeks including a 2-week screening, a 26-week randomized active-controlled treatment period, and 3-day post-treatment safety follow-up period.
Interventions
DRUGINSULIN GLARGINE/LIXISENATIDE HOE901/AVE0010
Pharmaceutical form: Solution for injection Route of administration: Subcutaneous
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult subject ≥ 18 years * Patients with type 2 diabetes mellitus (T2DM) based on Diabetes Canada 2018 Clinical Practice Guidelines criteria and diagnosed at least 6 months prior to the screening visit * Uncontrolled glycemia with an A1c ≥7.5% and ≤10.5% * Patients treated for at least 6 months on any basal insulin (including but not limited to insulin glargine, Toujeo®, Degludec®, etc.) ± oral anti-diabetic drug (OADs) * The total basal insulin dose must be ≤ 40 units/day * The OADs allowed at inclusion are metformin, insulin secretagogues, dipeptidyl-peptidase-4 inhibitors (DPP4) inhibitors and SGLT2 inhibitors; with no change in OAD dose for at least 2 months prior to randomization * Body mass index (BMI) between 20 kg/m2 and 40 kg/m2 inclusively
Exclusion criteria
* History of severe hypoglycemia or hypoglycemia unawareness * History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening visit * Current or previous (known intolerance to GLP-1s) treatment with glucagon like peptide-1 (GLP-1) receptor agonist * Current use of rapid-acting insulin or premix insulins or use of these insulins within 3 months prior to the screening visit * Use of systemic glucocorticoids (excluding topical and inhaled forms) for a total duration of 1 week or more within 3 months prior to the screening visit * Use of weight loss drugs within 3 months prior to the screening visit * Patients with conditions/concomitant diseases that will affect safe participation in this study (e.g. active malignant tumor, major systemic diseases, presence of clinically significant diabetic retinopathy or presence of macular edema likely to require treatment within the study period, etc.) * Women of childbearing potential (WOCBP) not protected by an effective contraceptive method of birth control and/or who are unwilling or unable to be tested for pregnancy * Positive serum pregnancy test in WOCBP, pregnancy or lactation * Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including (but not limited to): gastroparesis, unstable (i.e. worsening) or uncontrolled (i.e. prolonged nausea and vomiting) gastroesophageal reflux disease requiring medical treatment within 6 months prior to the time of screening visit * History of pancreatitis (unless pancreatitis was related to gallstones and treated with cholecystectomy), pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, pancreatectomy, or stomach/gastric surgery * Personal or immediate family history of medullary thyroid cancer or genetic conditions that predispose the patient to medullary thyroid cancer (e.g. multiple endocrine neoplasia syndromes) The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in glycated hemoglobin (HbA1c)% | Baseline to Week 26 | Absolute mean change in HbA1c from baseline to Week 26; HbA1c is expressed in % (unit) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in fasting plasma glucose (FPG) from baseline to Week 12 | Baseline to Week 12 | Change in FPG from baseline to Week 12 |
| Change in FPG from baseline to Week 26 | Baseline to Week 26 | Change in FPG from baseline to Week 26 |
| Change in fasting self-monitoring plasma glucose (SMPG) from baseline to Week 12 | Baseline to Week 12 | Change in fasting SMPG from baseline to Week 12 |
| Change in fasting SMPG from baseline to Week 26 | Baseline to Week 26 | Change in fasting SMPG from baseline to Week 26 |
| Change in 7-point SMPG profile from baseline to Week 12 | Baseline to Week 12 | Change in 7-point SMPG profile from baseline to Week 12 |
| Change in 7-point SMPG profile from baseline to Week 26 | Baseline to Week 26 | Change in 7-point SMPG profile from baseline to Week 26 |
| Change in body weight from baseline to Week 26 | Baseline to Week 26 | Change in body weight (kg) |
| Percentage of patients achieving HbA1c ≤7% at Week 26 | At Week 26 | Percentage of patients achieving A1c ≤7% |
| Insulin glargine dose | At Week 26 | Insulin glargine dose (expressed in units) |
| Percentage of patients requiring rescue therapy | Baseline to Week 26 | Percentage of patients requiring rescue therapy during the 26-week open-label treatment period |
| Percentage of patients experiencing at least 1 hypoglycemia episode (≤3.9 mmol/L) over 26 weeks | Baseline to Week 26 | Percentage of patients experiencing at least 1 hypoglycemia episode defined as ≤3.9 mmol/L |
| Percentage of patients experiencing at least 1 hypoglycemia episode (<3.0 mmol/L) over 26 weeks | Baseline to Week 26 | Percentage of patients experiencing at least 1 hypoglycemia episode defined as \<3.0 mmol/L |
| Annualized rate of hypoglycemia (≤3.9 mmol/L) over 26 weeks | Baseline to Week 26 | Mean number of hypoglycemia episodes (≤3.9 mmol/L) per patient year of exposure over 1 year |
| Annualized rate of hypoglycemia (<3.0 mmol/L) over 26 weeks | Baseline to Week 26 | Mean number of hypoglycemia episodes (\<3.0 mmol/L) per patient year of exposure over 1 year |
| Percentage of patients achieving A1c ≤7% with no body weight gain and/or hypoglycemia (severe or documented symptomatic (≤3.9 mmol/L) at Week 26 | Baseline to Week 26 | Composite endpoint expressed as percentage of patients A1c ≤7% with no body weight gain and/or hypoglycemia (severe or documented symptomatic (≤3.9 mmol/L) |
Countries
Canada
Outcome results
None listed