Clinical trial NCT03767543: 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)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2018-12-06
Enrollment: 265
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in glycated hemoglobin (HbA1c)%
timeFrame: Baseline to Week 26
Secondary outcomes:
measure: Percentage of patients achieving HbA1c ≤7% at Week 26
timeFrame: At Week 26
measure: Change in fasting plasma glucose (FPG) from baseline to Week 12
timeFrame: Baseline to Week 12
measure: Change in FPG from baseline to Week 26
timeFrame: Baseline to Week 26
measure: Change in fasting self-monitoring plasma glucose (SMPG) from baseline to Week 12
timeFrame: Baseline to Week 12
measure: Change in fasting SMPG from baseline to Week 26
timeFrame: Baseline to Week 26
measure: Change in 7-point SMPG profile from baseline to Week 12
timeFrame: Baseline to Week 12
measure: Change in 7-point SMPG profile from baseline to Week 26
timeFrame: Baseline to Week 26
measure: Change in body weight from baseline to Week 26
timeFrame: Baseline to Week 26
measure: 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
timeFrame: Baseline to Week 26
measure: Insulin glargine dose
timeFrame: At Week 26
measure: Percentage of patients requiring rescue therapy
timeFrame: Baseline to Week 26
measure: Percentage of patients experiencing at least 1 hypoglycemia episode (≤3.9 mmol/L) over 26 weeks
timeFrame: Baseline to Week 26
measure: Percentage of patients experiencing at least 1 hypoglycemia episode (<3.0 mmol/L) over 26 weeks
timeFrame: Baseline to Week 26
measure: Annualized rate of hypoglycemia (≤3.9 mmol/L) over 26 weeks
timeFrame: Baseline to Week 26
measure: Annualized rate of hypoglycemia (<3.0 mmol/L) over 26 weeks
timeFrame: Baseline to Week 26
Other outcomes:
Locations:
city: Barrie
country: Canada
facility: Investigational Site Number 1240004
city: Brampton
country: Canada
facility: Investigational Site Number 1240006
city: Brampton
country: Canada
facility: Investigational Site Number 1240002
city: Burlington
country: Canada
facility: Investigational Site Number 1240005
city: Calgary
country: Canada
facility: Investigational Site Number 1240003
city: Chicoutimi
country: Canada
facility: Investigational Site Number 1240024
city: Concord
country: Canada
facility: Investigational Site Number 1240014
city: Etobicoke
country: Canada
facility: Investigational Site Number 1240017
city: Greenfield Park
country: Canada
facility: Investigational Site Number 1240030
city: Halifax
country: Canada
facility: Investigational Site Number 1240031
city: Hamilton
country: Canada
facility: Investigational Site Number 1240026
city: Laval
country: Canada
facility: Investigational Site Number 1240011
city: London
country: Canada
facility: Investigational Site Number 1240016
city: London
country: Canada
facility: Investigational Site Number 1240015
city: Mirabel
country: Canada
facility: Investigational Site Number 1240019
city: Montreal
country: Canada
facility: Investigational Site Number 1240018
city: Montreal
country: Canada
facility: Investigational Site Number 1240023
city: Montreal
country: Canada
facility: Investigational Site Number 1240020
city: Montreal
country: Canada
facility: Investigational Site Number 1240029
city: Nepan
country: Canada
facility: Investigational Site Number 1240027
city: Newmarket
country: Canada
facility: Investigational Site Number 1240025
city: Oakville
country: Canada
facility: Investigational Site Number 1240021
city: Oshawa
country: Canada
facility: Investigational Site Number 1240009
city: Quebec
country: Canada
facility: Investigational Site Number 1240008
city: Quebec
country: Canada
facility: Investigational Site Number 1240022
city: Saint-Lambert
country: Canada
facility: Investigational Site Number 1240028
city: St-Marc-des-Carrieres
country: Canada
facility: Investigational Site Number 1240013
city: Toronto
country: Canada
facility: Investigational Site Number 1240033
city: Toronto
country: Canada
facility: Investigational Site Number 1240001
city: Vancouver
country: Canada
facility: Investigational Site Number 1240012
city: Victoriaville
country: Canada
facility: Investigational Site Number 1240007
city: Winnipeg
country: Canada
facility: Investigational Site Number 1240032
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.