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

NCT ID: NCT03798080

Last Updated: 2022-07-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

426 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-02-19

Study Completion Date

2020-12-01

Brief Summary

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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

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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.

Conditions

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Type 2 Diabetes Mellitus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Soliqua (insulin glargine/lixisenatide)

iGlarLixi (insulin glargine/lixisenatide) will be self-administered subcutaneously once daily in the morning with or without metformin for 30 weeks

Group Type EXPERIMENTAL

Insulin glargine/Lixisenatide (HOE901/AVE0010)

Intervention Type DRUG

Pharmaceutical form: solution

Route of administration: subcutaneous

Metformin

Intervention Type DRUG

Pharmaceutical form: tablet

Route of administration: oral

Lantus (insulin glargine)

Insulin glargine will be self-administered subcutaneously once daily at any time of the day with or without metformin for 30 weeks

Group Type ACTIVE_COMPARATOR

Insulin glargine (HOE901)

Intervention Type DRUG

Pharmaceutical form: solution

Route of administration: subcutaneous

Metformin

Intervention Type DRUG

Pharmaceutical form: tablet

Route of administration: oral

Interventions

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Insulin glargine/Lixisenatide (HOE901/AVE0010)

Pharmaceutical form: solution

Route of administration: subcutaneous

Intervention Type DRUG

Insulin glargine (HOE901)

Pharmaceutical form: solution

Route of administration: subcutaneous

Intervention Type DRUG

Metformin

Pharmaceutical form: tablet

Route of administration: oral

Intervention Type DRUG

Other Intervention Names

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Soliqua iGlarLixi Lantus

Eligibility Criteria

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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.

* 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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sanofi

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

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Investigational Site Number 1560044

Baotou, , China

Site Status

Investigational Site Number 1560001

Beijing, , China

Site Status

Investigational Site Number 1560039

Beijing, , China

Site Status

Investigational Site Number 1560005

Changchun, , China

Site Status

Investigational Site Number 1560054

Changchun, , China

Site Status

Investigational Site Number 1560015

Changsha, , China

Site Status

Investigational Site Number 1560010

Chenzhou, , China

Site Status

Investigational Site Number 1560030

Chongqing, , China

Site Status

Investigational Site Number 1560025

Fuzhou, , China

Site Status

Investigational Site Number 1560016

Guangzhou, , China

Site Status

Investigational Site Number 1560053

Guangzhou, , China

Site Status

Investigational Site Number 1560045

Guangzhou, , China

Site Status

Investigational Site Number 1560021

Hefei, , China

Site Status

Investigational Site Number 1560018

Hohhot, , China

Site Status

Investigational Site Number 1560019

Huanggang, , China

Site Status

Investigational Site Number 1560041

Jiaxing, , China

Site Status

Investigational Site Number 1560040

Jinan, , China

Site Status

Investigational Site Number 1560007

Jinan, , China

Site Status

Investigational Site Number 1560026

Jinzhou, , China

Site Status

Investigational Site Number 1560042

Kaifeng, , China

Site Status

Investigational Site Number 1560003

Kunming, , China

Site Status

Investigational Site Number 1560032

Lanzhou, , China

Site Status

Investigational Site Number 1560033

Luoyang, , China

Site Status

Investigational Site Number 1560028

Nanjing, , China

Site Status

Investigational Site Number 1560013

Nanjing, , China

Site Status

Investigational Site Number 1560017

Nanjing, , China

Site Status

Investigational Site Number 1560035

Nanjing, , China

Site Status

Investigational Site Number 1560038

Nanjing, , China

Site Status

Investigational Site Number 1560046

Nantong, , China

Site Status

Investigational Site Number 1560008

Pingxiang, , China

Site Status

Investigational Site Number 1560037

Qingdao, , China

Site Status

Investigational Site Number 1560031

Qinhuangdao, , China

Site Status

Investigational Site Number 1560011

Shanghai, , China

Site Status

Investigational Site Number 1560002

Shanghai, , China

Site Status

Investigational Site Number 1560027

Shanghai, , China

Site Status

Investigational Site Number 1560047

Shanghai, , China

Site Status

Investigational Site Number 1560012

Shenyang, , China

Site Status

Investigational Site Number 1560006

Tianjin, , China

Site Status

Investigational Site Number 1560049

Ürümqi, , China

Site Status

Investigational Site Number 1560020

Xining, , China

Site Status

Investigational Site Number 1560050

Xining, , China

Site Status

Investigational Site Number 1560036

Xuzhou, , China

Site Status

Investigational Site Number 1560023

Yangzhou, , China

Site Status

Investigational Site Number 1560022

Zhuzhou, , China

Site Status

Investigational Site Number 1560052

Zigong, , China

Site Status

Countries

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China

References

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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.

Reference Type BACKGROUND
PMID: 35762489 (View on PubMed)

Yuan X, Li D, Wang K, Lauand F, Zhang M, Fang H, Du Q, Kang L, Alvarez A, Guo X. iGlarLixi effectively reduces residual hyperglycaemia in Chinese people with type 2 diabetes on basal insulin: A post hoc analysis of the LixiLan-L-CN study. Diabetes Obes Metab. 2024 Dec;26(12):5942-5949. doi: 10.1111/dom.15968. Epub 2024 Oct 3.

Reference Type DERIVED
PMID: 39360440 (View on PubMed)

Guo X, Yang W, Zhang J, Dong X, Liu M, Gu S, Lauand F, Li L, Huang Q, Kang L, Souhami E. iGlarLixi provides a higher derived time-in-range versus insulin glargine 100 U/mL or lixisenatide in Asian Pacific people with type 2 diabetes: A post hoc analysis. Diabetes Obes Metab. 2023 Jul;25(7):2005-2011. doi: 10.1111/dom.15074. Epub 2023 May 3.

Reference Type DERIVED
PMID: 36999231 (View on PubMed)

Other Identifiers

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U1111-1190-7781

Identifier Type: OTHER

Identifier Source: secondary_id

EFC14944

Identifier Type: -

Identifier Source: org_study_id

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