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

Type 2 Diabetes Mellitus Clinical Trial

— Lixilan-L-CN  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03798080
• Other study ID #: EFC14944
• Secondary ID: U1111-1190-7781
• Status: Completed
• Phase: Phase 3
• Start date: February 19, 2019
• Est. completion date: December 1, 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 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 426
• Est. completion date: December 1, 2020
• Est. primary completion date: December 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Insulin glargine/Lixisenatide (HOE901/AVE0010)
Pharmaceutical form: solution Route of administration: subcutaneous
• Insulin glargine (HOE901)
Pharmaceutical form: solution Route of administration: subcutaneous
• Metformin
Pharmaceutical form: tablet Route of administration: oral

Locations

Country	Name	City	State
China	Investigational Site Number 1560044	Baotou
China	Investigational Site Number 1560001	Beijing
China	Investigational Site Number 1560039	Beijing
China	Investigational Site Number 1560005	Changchun
China	Investigational Site Number 1560054	Changchun
China	Investigational Site Number 1560015	Changsha
China	Investigational Site Number 1560010	Chenzhou
China	Investigational Site Number 1560030	Chongqing
China	Investigational Site Number 1560025	Fuzhou
China	Investigational Site Number 1560016	Guangzhou
China	Investigational Site Number 1560045	Guangzhou
China	Investigational Site Number 1560053	Guangzhou
China	Investigational Site Number 1560021	Hefei
China	Investigational Site Number 1560018	Hohhot
China	Investigational Site Number 1560019	Huanggang
China	Investigational Site Number 1560041	Jiaxing
China	Investigational Site Number 1560007	Jinan
China	Investigational Site Number 1560040	Jinan
China	Investigational Site Number 1560026	Jinzhou
China	Investigational Site Number 1560042	Kaifeng
China	Investigational Site Number 1560003	Kunming
China	Investigational Site Number 1560032	Lanzhou
China	Investigational Site Number 1560033	Luoyang
China	Investigational Site Number 1560013	Nanjing
China	Investigational Site Number 1560017	Nanjing
China	Investigational Site Number 1560028	Nanjing
China	Investigational Site Number 1560035	Nanjing
China	Investigational Site Number 1560038	Nanjing
China	Investigational Site Number 1560046	Nantong
China	Investigational Site Number 1560008	Pingxiang
China	Investigational Site Number 1560037	Qingdao
China	Investigational Site Number 1560031	Qinhuangdao
China	Investigational Site Number 1560002	Shanghai
China	Investigational Site Number 1560011	Shanghai
China	Investigational Site Number 1560027	Shanghai
China	Investigational Site Number 1560047	Shanghai
China	Investigational Site Number 1560012	Shenyang
China	Investigational Site Number 1560006	Tianjin
China	Investigational Site Number 1560049	Urumqi
China	Investigational Site Number 1560020	Xining
China	Investigational Site Number 1560050	Xining
China	Investigational Site Number 1560036	Xuzhou
China	Investigational Site Number 1560023	Yangzhou
China	Investigational Site Number 1560022	Zhuzhou
China	Investigational Site Number 1560052	Zigong

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

China, 

References & Publications (1)

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 Jun 28. doi: 10.1111/dom.14803. [Epub ahead of print] — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c	Change in glycated hemoglobin (HbA1c) from baseline to Week 30	From Baseline to Week 30
Secondary	Patients with HbA1c <7.0%	Percentage of patients reaching HbA1c <7% at Week 30	At Week 30
Secondary	Patients with HbA1c = 6.5%	Percentage of patients reaching HbA1c = 6.5% at Week 30	At Week 30
Secondary	Change in postprandial plasma glucose (PPG)	Absolute change in 2-hour blood glucose excursion and PPG during meal test from baseline to Week 30	From Baseline to Week 30
Secondary	Change in self-monitored plasma glucose (SMPG) profile	Absolute change in 7-point SMPG profiles from baseline to Week 30 (each time point and average daily value)	From Baseline to Week 30
Secondary	Patients with HbA1c <7.0% with no body weight gain	Percentage of patients reaching HbA1c <7% with no body weight gain at Week 30	At Week 30
Secondary	Change in body weight	Absolute change in body weight from baseline to Week 30	From Baseline to Week 30
Secondary	Patients with HbA1c <7.0% with no body weight gain and no documented symptomatic hypoglycemia	Percentage of patients reaching HbA1c <7% with no body weight gain at Week 30 and no documented (plasma glucose [PG] =70 mg/dL [3.9mmol/L]) symptomatic hypoglycemia during the 30-week randomized treatment period	At Week 30
Secondary	Patients requiring rescue therapy	Percentage of patients requiring rescue therapy during the 30-week randomized treatment period	From Baseline to Week 30
Secondary	Change in fasting plasma glucose (FPG)	Absolute change in FPG from baseline to Week 30	From Baseline to Week 30
Secondary	Confirmed hypoglycemia	Severe hypoglycemia and episodes of hypoglycemia documented with PG = 70 mg/dL (3.9mmol/L) regardless of symptoms	From Baseline to Week 30
Secondary	Adverse events (AEs)	Number of AEs, Serious AEs, AEs of Special Interest, and AEs requiring specific monitoring from baseline to Week 30	From Baseline to Week 30
Secondary	Immunogenicity (antibody variables)	Anti-lixisenatide antibodies (in iGlarLixi group) and anti-insulin antibodies from baseline to Week 30	From Baseline to Week 30