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) (LixilanOne CAN)

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)

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).

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: INSULIN GLARGINE/LIXISENATIDE HOE901/AVE0010

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.

• Study Type: Interventional
• Enrollment (Actual): 265
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Barrie, Canada, L4N4L3
    • Investigational Site Number 1240004
  • Brampton, Canada, L6S0C9
    • Investigational Site Number 1240006
  • Brampton, Canada, L6T4V3
    • Investigational Site Number 1240002
  • Burlington, Canada, L7R1A4
    • Investigational Site Number 1240005
  • Calgary, Canada, T2H2G4
    • Investigational Site Number 1240003
  • Chicoutimi, Canada, G7H7K9
    • Investigational Site Number 1240024
  • Concord, Canada, L4K4M2
    • Investigational Site Number 1240014
  • Etobicoke, Canada, M9R4E1
    • Investigational Site Number 1240017
  • Greenfield Park, Canada, J4V2G8
    • Investigational Site Number 1240030
  • Halifax, Canada, B3H1V7
    • Investigational Site Number 1240031
  • Hamilton, Canada, L8S4K1
    • Investigational Site Number 1240026
  • Laval, Canada, H7T 2P5
    • Investigational Site Number 1240011
  • London, Canada, N6A 4V2
    • Investigational Site Number 1240016
  • London, Canada, N6G 4X8
    • Investigational Site Number 1240015
  • Mirabel, Canada, J7J2K8
    • Investigational Site Number 1240019
  • Montreal, Canada, H1M1B1
    • Investigational Site Number 1240018
  • Montreal, Canada, H4A2C6
    • Investigational Site Number 1240023
  • Montreal, Canada, H4A3T2
    • Investigational Site Number 1240020
  • Montreal, Canada, H4T1Z9
    • Investigational Site Number 1240029
  • Nepan, Canada, K2J0V2
    • Investigational Site Number 1240027
  • Newmarket, Canada
    • Investigational Site Number 1240025
  • Oakville, Canada, L6M1M1
    • Investigational Site Number 1240021
  • Oshawa, Canada, L1H7K4
    • Investigational Site Number 1240009
  • Quebec, Canada, G1G3Y8
    • Investigational Site Number 1240008
  • Quebec, Canada, G1V4W2
    • Investigational Site Number 1240022
  • Saint-Lambert, Canada, J4P2H4
    • Investigational Site Number 1240028
  • St-Marc-des-Carrieres, Canada
    • Investigational Site Number 1240013
  • Toronto, Canada, M3J0K2
    • Investigational Site Number 1240033
  • Toronto, Canada, M4G3E8
    • Investigational Site Number 1240001
  • Vancouver, Canada, V5Y3W2
    • Investigational Site Number 1240012
  • Victoriaville, Canada, G6P6P6
    • Investigational Site Number 1240007
  • Winnipeg, Canada, R2V4W3
    • Investigational Site Number 1240032

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: iGlarlixi DAILY; Titration Group 1: Addition of 1 unit per day until pre-stated fasting self-monitoring plasma glucose (SMBG) level is reached	Drug: INSULIN GLARGINE/LIXISENATIDE HOE901/AVE0010; Pharmaceutical form: Solution for injection Route of administration: Subcutaneous
ACTIVE_COMPARATOR: iGlarlixi WEEKLY; Titration Group 2: Algorithm of weekly adjustment until pre-stated fasting self-monitoring plasma glucose (SMBG) level is reached	Drug: INSULIN GLARGINE/LIXISENATIDE HOE901/AVE0010; Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients achieving HbA1c ≤7% at Week 26	Percentage of patients achieving A1c ≤7%	At Week 26
Change in fasting plasma glucose (FPG) from baseline to Week 12	Change in FPG from baseline to Week 12	Baseline to Week 12
Change in FPG from baseline to Week 26	Change in FPG from baseline to Week 26	Baseline to Week 26
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
Change in fasting SMPG from baseline to Week 26	Change in fasting SMPG from baseline to Week 26	Baseline to Week 26
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
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
Change in body weight from baseline to Week 26	Change in body weight (kg)	Baseline to Week 26
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
Insulin glargine dose	Insulin glargine dose (expressed in units)	At Week 26
Percentage of patients requiring rescue therapy	Percentage of patients requiring rescue therapy during the 26-week open-label treatment period	Baseline to Week 26
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
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
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
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

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Hramiak I, Gerstein HC, Leiter LA, Yale JF, Bajaj HS, Stewart J, Toutounji MJ, Harris SB. Comparing a daily versus weekly titration algorithm in people with type 2 diabetes switching from basal insulin to iGlarLixi in the LixiLan ONE CAN randomized trial. Diabetes Obes Metab. 2022 Oct;24(10):1998-2007. doi: 10.1111/dom.14787. Epub 2022 Jun 29.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 11, 2019
• Primary Completion (ACTUAL): October 23, 2020
• Study Completion (ACTUAL): October 23, 2020

Study Registration Dates

• First Submitted: December 5, 2018
• First Submitted That Met QC Criteria: December 5, 2018
• First Posted (ACTUAL): December 6, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 21, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Glargine; Lixisenatide
• Other Study ID Numbers: LPS15544; U1111-1215-0238 (OTHER: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No