Clinical trial NCT03798080: Comparison of the Efficacy and Safety of Insulin Glargine/Lixisenatide Fixed Ratio Combination to Insulin Glargine in Patients With Type 2 Diabetes Insufficiently Controlled on Basal Insulin
Official title: A Randomized, 30-week, Active-controlled, Open-label, 2 Treatment-arm, Parallel Group, Multicenter Study Comparing Efficacy and Safety of iGlarLixi to Insulin Glargine With or Without Metformin in Patients With Type 2 Diabetes Mellitus Insufficiently Controlled on Basal Insulin With or Without Oral Antidiabetic Drug(s)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2019-01-09
Enrollment: 426
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 the superiority of iGlarLixi (fixed ratio combination of insulin glargine and lixisenatide) to insulin glargine on glycemic control as assessed by glycated hemoglobin A1c (HbA1c) change in patients with type 2 diabetes mellitus (T2DM) who are not sufficiently controlled with basal insulin.

Secondary Objectives:

* To assess the effects of iGlarLixi in comparison with insulin glargine
* To assess the safety in each treatment group

Detailed description: The maximum study duration per patient will be approximately 33 weeks: an up to 2-week screening period (it can be exceptionally extended up to one additional week), a 30-week, open label randomized treatment period comparing iGlarLixi to insulin glargine (± metformin for both treatments), and a 3-day post-treatment safety follow-up period.

Eligibility criteria: Inclusion criteria :

* Patients with type 2 diabetes mellitus (T2DM) diagnosed for at least 1 year and treated with basal insulin for at least 6 months before screening visit (V1).
* Patients who have been treated with a stable basal insulin regimen (ie, type of insulin and time/frequency of the injection), for at least 3 months before screening visit (V1).
* Stable total daily basal insulin dose (±20 %) in the range of 10 and 25 U/day for at least 2 months before screening visit (V1). Total daily dose should be within the range of 10-25 U, both inclusive, on the day of screening, but individual fluctuations of ±20% within 2 months prior to screening are acceptable.
* For patients receiving basal insulin AND 1 or 2 oral anti-diabetic drugs (OADs): the OAD dose(s) must be stable during the 3 months prior to screening. The OAD(s) can be 1 to 2 out of:
* Metformin (≥1500 mg/day or maximal tolerated dose).
* Sulfonylurea (SU)/glinide.
* Alpha-glucosidase inhibitor (alpha-GI).
* Sodium-glucose co-transporter 2 (SGLT2) inhibitor.
* Dipeptidyl-peptidase-4 (DPP-4) inhibitor.
* Fasting plasma glucose (FPG) ≤160 mg/dL (8.9 mmol/L) at screening visit (V1) (can be repeated once to confirm).
* Signed written informed consent.

Exclusion criteria:

* Age \<18 years at screening visit (V1).
* Screening glycated hemoglobin A1c(HbA1c) \<7.0% or \>10.5%.
* History of hypoglycemia unawareness.
* History of metabolic acidosis, including diabetic ketoacidosis within one year prior to screening.
* Use of oral or injectable glucose-lowering agents other than those stated in the inclusion criteria within 3 months prior to screening.
* Previous use of insulin regimen other than basal insulin, eg, prandial or pre-mixed insulin, within one year prior to screening (Note: Short term treatment \[≤10 days\] due to intercurrent illness is allowed).
* History of discontinuation of a previous treatment with glucagon-like-peptide-1 receptor agonists (GLP-1 RAs) due to safety/tolerability reason or lack of efficacy.
* Use of systemic glucocorticoids (excluding topical application or inhaled forms) for 1 week or more within 3 months prior to screening.
* Use of weight loss drugs within 3 months prior to screening.
* Use of any investigational drug within 1 month or 5 half-lives, whichever is longer, prior to screening.
* Within 6 months prior to screening: history of myocardial infarction, stroke, or heart failure requiring hospitalization.
* Planned coronary, carotid, or peripheral revascularization procedures to be performed during the study period.
* Known history of drug or alcohol abuse within 6 months prior to screening.
* Uncontrolled or inadequately controlled hypertension at the time of screening with a resting systolic blood pressure \>180 mmHg or diastolic blood pressure \>95 mmHg.
* Laboratory findings at screening visit:
* Amylase and/or lipase \>3 times the upper limit of normal (ULN) laboratory range.
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 ULN.
* Total bilirubin \>1.5 ULN (except in case of Gilbert's syndrome).
* Calcitonin ≥20 pg/mL (5.9 pmol/L).
* Hemoglobin \<10.5 g/dL and/or neutrophils \<1500/mm3 and/or platelets \<100 000/mm3.
* Positive test for hepatitis B surface antigen (HBsAg) and/or hepatitis C antibody (HCAb).
* Positive urine pregnancy test in female of childbearing potential.
* For patient not treated with metformin at screening: severe renal function impairment with an estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73m2 or end-stage renal disease.
* Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including (but not limited to): gastroparesis, unstable (ie, worsening) or not controlled (ie, prolonged nausea and vomiting) gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening visit; or history of surgery affecting gastric emptying.
* History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy has been performed), pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, pancreatectomy.
* Personal or immediate family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (eg, multiple endocrine neoplasia syndromes).
* Mean fasting self-monitored plasma glucose (SMPG) is \>160 mg/dL (8.9 mmol/L), calculated from all available (minimum of 4 self-measurements) values during the 7 days prior to randomization.

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 HbA1c
timeFrame: From Baseline to Week 30
Secondary outcomes:
measure: Patients with HbA1c <7.0%
timeFrame: At Week 30
measure: Patients with HbA1c ≤ 6.5%
timeFrame: At Week 30
measure: Change in postprandial plasma glucose (PPG)
timeFrame: From Baseline to Week 30
measure: Change in self-monitored plasma glucose (SMPG) profile
timeFrame: From Baseline to Week 30
measure: Patients with HbA1c <7.0% with no body weight gain
timeFrame: At Week 30
measure: Change in body weight
timeFrame: From Baseline to Week 30
measure: Patients with HbA1c <7.0% with no body weight gain and no documented symptomatic hypoglycemia
timeFrame: At Week 30
measure: Patients requiring rescue therapy
timeFrame: From Baseline to Week 30
measure: Change in fasting plasma glucose (FPG)
timeFrame: From Baseline to Week 30
measure: Confirmed hypoglycemia
timeFrame: From Baseline to Week 30
measure: Adverse events (AEs)
timeFrame: From Baseline to Week 30
measure: Immunogenicity (antibody variables)
timeFrame: From Baseline to Week 30
Other outcomes:
Locations:
city: Baotou
country: China
facility: Investigational Site Number 1560044
city: Beijing
country: China
facility: Investigational Site Number 1560001
city: Beijing
country: China
facility: Investigational Site Number 1560039
city: Changchun
country: China
facility: Investigational Site Number 1560005
city: Changchun
country: China
facility: Investigational Site Number 1560054
city: Changsha
country: China
facility: Investigational Site Number 1560015
city: Chenzhou
country: China
facility: Investigational Site Number 1560010
city: Chongqing
country: China
facility: Investigational Site Number 1560030
city: Fuzhou
country: China
facility: Investigational Site Number 1560025
city: Guangzhou
country: China
facility: Investigational Site Number 1560016
city: Guangzhou
country: China
facility: Investigational Site Number 1560053
city: Guangzhou
country: China
facility: Investigational Site Number 1560045
city: Hefei
country: China
facility: Investigational Site Number 1560021
city: Hohhot
country: China
facility: Investigational Site Number 1560018
city: Huanggang
country: China
facility: Investigational Site Number 1560019
city: Jiaxing
country: China
facility: Investigational Site Number 1560041
city: Jinan
country: China
facility: Investigational Site Number 1560040
city: Jinan
country: China
facility: Investigational Site Number 1560007
city: Jinzhou
country: China
facility: Investigational Site Number 1560026
city: Kaifeng
country: China
facility: Investigational Site Number 1560042
city: Kunming
country: China
facility: Investigational Site Number 1560003
city: Lanzhou
country: China
facility: Investigational Site Number 1560032
city: Luoyang
country: China
facility: Investigational Site Number 1560033
city: Nanjing
country: China
facility: Investigational Site Number 1560028
city: Nanjing
country: China
facility: Investigational Site Number 1560013
city: Nanjing
country: China
facility: Investigational Site Number 1560017
city: Nanjing
country: China
facility: Investigational Site Number 1560035
city: Nanjing
country: China
facility: Investigational Site Number 1560038
city: Nantong
country: China
facility: Investigational Site Number 1560046
city: Pingxiang
country: China
facility: Investigational Site Number 1560008
city: Qingdao
country: China
facility: Investigational Site Number 1560037
city: Qinhuangdao
country: China
facility: Investigational Site Number 1560031
city: Shanghai
country: China
facility: Investigational Site Number 1560011
city: Shanghai
country: China
facility: Investigational Site Number 1560002
city: Shanghai
country: China
facility: Investigational Site Number 1560027
city: Shanghai
country: China
facility: Investigational Site Number 1560047
city: Shenyang
country: China
facility: Investigational Site Number 1560012
city: Tianjin
country: China
facility: Investigational Site Number 1560006
city: Urumqi
country: China
facility: Investigational Site Number 1560049
city: Xining
country: China
facility: Investigational Site Number 1560020
city: Xining
country: China
facility: Investigational Site Number 1560050
city: Xuzhou
country: China
facility: Investigational Site Number 1560036
city: Yangzhou
country: China
facility: Investigational Site Number 1560023
city: Zhuzhou
country: China
facility: Investigational Site Number 1560022
city: Zigong
country: China
facility: Investigational Site Number 1560052
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Yuan X, Guo X, Zhang J, Dong X, Lu Y, Pang W, Gu S, Niemoeller E, Ping L, Nian G, Souhami E; LixiLan-L-CN investigators. Improved glycaemic control and weight benefit with iGlarLixi versus insulin glargine 100 U/mL in Chinese people with type 2 diabetes advancing their therapy from basal insulin plus oral antihyperglycaemic drugs: Results from the LixiLan-L-CN randomized controlled trial. Diabetes Obes Metab. 2022 Nov;24(11):2182-2191. doi: 10.1111/dom.14803. Epub 2022 Jul 25.