Study Comparing the Efficacy and Safety of Insulin Glargine (Basal Insulin)/Lixisenatide (GLP-1 Receptor Agonist) Combination (Soliqua™) in Patients With Type 2 Diabetes Mellitus (T2DM)

Type 2 Diabetes Mellitus Clinical Trial

— LixilanOne CAN  

Official title:

A Randomized, 26-week, Open-label, 2-treatment Arm, Parallel Group Multicenter Study Comparing the Efficacy and Safety of Insulin Glargine/Lixisenatide Fixed-ratio Combination (Soliqua™) Titrated Using a Simple Titration Algorithm (One Unit Daily Adjustment) Compared With Insulin Glargine/Lixisenatide Fixed-ratio Combination (Soliqua™) Titrated by Weekly Adjustment in Patients With Type 2 Diabetes Mellitus (T2DM)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03767543
• Other study ID #: LPS15544
• Secondary ID: U1111-1215-0238
• Status: Completed
• Phase: Phase 3
• Start date: March 11, 2019
• Est. completion date: October 23, 2020

Study information

• Verified date: April 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 265
• Est. completion date: October 23, 2020
• Est. primary completion date: October 23, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• INSULIN GLARGINE/LIXISENATIDE HOE901/AVE0010
Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

Locations

Country	Name	City	State
Canada	Investigational Site Number 1240004	Barrie
Canada	Investigational Site Number 1240002	Brampton
Canada	Investigational Site Number 1240006	Brampton
Canada	Investigational Site Number 1240005	Burlington
Canada	Investigational Site Number 1240003	Calgary
Canada	Investigational Site Number 1240024	Chicoutimi
Canada	Investigational Site Number 1240014	Concord
Canada	Investigational Site Number 1240017	Etobicoke
Canada	Investigational Site Number 1240030	Greenfield Park
Canada	Investigational Site Number 1240031	Halifax
Canada	Investigational Site Number 1240026	Hamilton
Canada	Investigational Site Number 1240011	Laval
Canada	Investigational Site Number 1240015	London
Canada	Investigational Site Number 1240016	London
Canada	Investigational Site Number 1240019	Mirabel
Canada	Investigational Site Number 1240018	Montreal
Canada	Investigational Site Number 1240020	Montreal
Canada	Investigational Site Number 1240023	Montreal
Canada	Investigational Site Number 1240029	Montreal
Canada	Investigational Site Number 1240027	Nepan
Canada	Investigational Site Number 1240025	Newmarket
Canada	Investigational Site Number 1240021	Oakville
Canada	Investigational Site Number 1240009	Oshawa
Canada	Investigational Site Number 1240008	Quebec
Canada	Investigational Site Number 1240022	Quebec
Canada	Investigational Site Number 1240028	Saint-Lambert
Canada	Investigational Site Number 1240013	St-Marc-des-Carrieres
Canada	Investigational Site Number 1240001	Toronto
Canada	Investigational Site Number 1240033	Toronto
Canada	Investigational Site Number 1240012	Vancouver
Canada	Investigational Site Number 1240007	Victoriaville
Canada	Investigational Site Number 1240032	Winnipeg

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in glycated hemoglobin (HbA1c)%	Absolute mean change in HbA1c from baseline to Week 26; HbA1c is expressed in % (unit)	Baseline to Week 26
Secondary	Percentage of patients achieving HbA1c =7% at Week 26	Percentage of patients achieving A1c =7%	At Week 26
Secondary	Change in fasting plasma glucose (FPG) from baseline to Week 12	Change in FPG from baseline to Week 12	Baseline to Week 12
Secondary	Change in FPG from baseline to Week 26	Change in FPG from baseline to Week 26	Baseline to Week 26
Secondary	Change in fasting self-monitoring plasma glucose (SMPG) from baseline to Week 12	Change in fasting SMPG from baseline to Week 12	Baseline to Week 12
Secondary	Change in fasting SMPG from baseline to Week 26	Change in fasting SMPG from baseline to Week 26	Baseline to Week 26
Secondary	Change in 7-point SMPG profile from baseline to Week 12	Change in 7-point SMPG profile from baseline to Week 12	Baseline to Week 12
Secondary	Change in 7-point SMPG profile from baseline to Week 26	Change in 7-point SMPG profile from baseline to Week 26	Baseline to Week 26
Secondary	Change in body weight from baseline to Week 26	Change in body weight (kg)	Baseline to Week 26
Secondary	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	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)	Baseline to Week 26
Secondary	Insulin glargine dose	Insulin glargine dose (expressed in units)	At Week 26
Secondary	Percentage of patients requiring rescue therapy	Percentage of patients requiring rescue therapy during the 26-week open-label treatment period	Baseline to Week 26
Secondary	Percentage of patients experiencing at least 1 hypoglycemia episode (=3.9 mmol/L) over 26 weeks	Percentage of patients experiencing at least 1 hypoglycemia episode defined as =3.9 mmol/L	Baseline to Week 26
Secondary	Percentage of patients experiencing at least 1 hypoglycemia episode (<3.0 mmol/L) over 26 weeks	Percentage of patients experiencing at least 1 hypoglycemia episode defined as <3.0 mmol/L	Baseline to Week 26
Secondary	Annualized rate of hypoglycemia (=3.9 mmol/L) over 26 weeks	Mean number of hypoglycemia episodes (=3.9 mmol/L) per patient year of exposure over 1 year	Baseline to Week 26
Secondary	Annualized rate of hypoglycemia (<3.0 mmol/L) over 26 weeks	Mean number of hypoglycemia episodes (<3.0 mmol/L) per patient year of exposure over 1 year	Baseline to Week 26