Evaluation of Insulin Glargine/Lixisenatide Fixed Ratio Combination in Patients With Type 2 Diabetes Insufficiently Controlled With Oral Antidiabetic Drug(s)

NCT03798054 | Completed Phase 3

• 2 other identifiers: EFC14943U1111-1190-7669
• Study Type: interventional
• Target: 878
• Locations: 4 countries
• Sites: 79

Brief Summary

Primary Objectives: The co-primary objective of this study is:

• To demonstrate the superiority of iGlarLixi (fixed ratio combination of insulin glargine and lixisenatide) versus lixisenatide on glycemic control as assessed by glycated hemoglobin A1c (HbA1c) change.
• To demonstrate the non-inferiority of iGlarLixi versus insulin glargine on glycemic control as assessed by HbA1c change. Secondary Objectives:
• To assess the effects of iGlarLixi in comparison with insulin glargine alone and lixisenatide alone.
• To assess the safety in each treatment group.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Change in HbA1c

  Change in glycated hemoglobin (HbA1c) from baseline to Week 24

  From Baseline to Week 24

Secondary Outcomes (11)

• Change in postprandial plasma glucose (PPG)

  From Baseline to Week 24

• Change in fasting plasma glucose (FPG)

  From Baseline to Week 24

• Change in self-monitored plasma glucose (SMPG) profile

  From Baseline to Week 24

• Patients with HbA1c <7.0%

  At Week 24

• Patients with HbA1c ≤ 6.5%

  At Week 24

Study Arms (3)

Soliqua (insulin glargine/lixisenatide)

EXPERIMENTAL

iGlarLixi (insulin glargine/lixisenatide) will be self-administered subcutaneously once daily in the morning on top of metformin for 24 weeks.

Drug: Insulin glargine/Lixisenatide (HOE901/AVE0010); Drug: Metformin; Drug: SGLT2 inhibitor

Lantus (insulin glargine)

ACTIVE COMPARATOR

Insulin glargine will be self-administered subcutaneously once daily at any time of the day on top of metformin for 24 weeks. Injection time should be determined on the day of randomization, and should remain about the same until the end of the treatment period.

Drug: Insulin glargine (HOE901); Drug: Metformin; Drug: SGLT2 inhibitor

Lyxumia (lixisenatide)

ACTIVE COMPARATOR

Lixisenatide will be self-administered subcutaneously once daily according to the locally approved label on top of metformin for 24 weeks. Injection time should be determined on the day of randomization, and should remain about the same until the end of the treatment period.

Drug: Lixisenatide (AVE0010); Drug: Metformin; Drug: SGLT2 inhibitor

Interventions

Insulin glargine/Lixisenatide (HOE901/AVE0010) DRUG

Pharmaceutical form: solution Route of administration: subcutaneous

Also known as: Soliqua, iGlarLixi

Soliqua (insulin glargine/lixisenatide)

Insulin glargine (HOE901) DRUG

Pharmaceutical form: solution Route of administration: subcutaneous

Also known as: Lantus

Lantus (insulin glargine)

Lixisenatide (AVE0010) DRUG

Pharmaceutical form: solution Route of administration: subcutaneous

Also known as: Lyxumia

Lyxumia (lixisenatide)

Metformin DRUG

Pharmaceutical form: tablet Route of administration: oral

Lantus (insulin glargine); Lyxumia (lixisenatide); Soliqua (insulin glargine/lixisenatide)

SGLT2 inhibitor DRUG

Pharmaceutical form:tablet Route of administration: oral

Lantus (insulin glargine); Lyxumia (lixisenatide); Soliqua (insulin glargine/lixisenatide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with type 2 diabetes mellitus (T2DM) diagnosed for at least 1 year before the screening visit (V1), treated for at least 3 months prior to the screening visit (V1) with metformin alone or metformin and a second oral antidiabetic treatment that can be a sulfonylurea (SU), a glinide, an alpha-glucosidase inhibitor (alpha-GI), a dipeptidyl peptidase-4 (DPP-4) inhibitor or a sodium-glucose co transporter 2 (SGLT-2) inhibitor and who are not adequately controlled with this treatment.
• Signed written informed consent.

You may not qualify if:

• Age \< legal age of majority at the screening visit (V1).
• Body mass index (BMI) \>40 kg/m² at screening.
• Glycated hemoglobin A1c (HbA1c) at screening visit:
• \<7.5% or \>11% for patients previously treated with metformin alone;
• \<7.0% or \>10% for patients previously treated with metformin and a second oral antidiabetic treatment.
• History of hypoglycemia unawareness.
• History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening.
• Previous treatment with insulin (except for short-term treatment due to intercurrent illness at the discretion of the Investigator) within 1 year prior to screening.
• History of discontinuation of a previous treatment with glucagon-like-peptide-1 receptor agonists (GLP-1 RAs) due to safety/tolerability reasons 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 other than specified in this protocol 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 artery revascularization procedures to be performed during the study period.
• Known history of drug or alcohol abuse within 6 months prior to screening.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (79)

Investigational Site Number 1560001

Beijing, 1000029, China

Location

Investigational Site Number 1560006

Beijing, 101200, China

Location

Investigational Site Number 1560049

Beijing, 102218, China

Location

Investigational Site Number 1560039

Cangzhou, 061000, China

Location

Investigational Site Number 1560009

Changchun, 130033, China

Location

Investigational Site Number 1560027

Changchun, 130041, China

Location

Investigational Site Number 1560016

Changsha, 410013, China

Location

Investigational Site Number 1560053

Chengdu, 610081, China

Location

Investigational Site Number 1560056

Chengdu, 611130, China

Location

Investigational Site Number 1560010

Chenzhou, China

Location

Investigational Site Number 1560037

Chongqing, 400010, China

Location

Investigational Site Number 1560050

Chongqing, 400013, China

Location

Investigational Site Number 1560044

Dongguan, China

Location

Investigational Site Number 1560033

Guangzhou, 510120, China

Location

Investigational Site Number 1560028

Guangzhou, China

Location

Investigational Site Number 1560012

Handan, 056002, China

Location

Investigational Site Number 1560023

Hangzhou, China

Location

Investigational Site Number 1560035

Harbin, 150001, China

Location

Investigational Site Number 1560036

Harbin, 150001, China

Location

Investigational Site Number 1560011

Hengshui, 053000, China

Location

Investigational Site Number 1560024

Hohhot, 010017, China

Location

Investigational Site Number 1560047

Hohhot, 010050, China

Location

Investigational Site Number 3440001

Hong Kong, China

Location

Investigational Site Number 1560026

Huanggang, China

Location

Investigational Site Number 1560025

Huangshi, China

Location

Investigational Site Number 1560048

Huizhou, 516001, China

Location

Investigational Site Number 1560034

Huzhou, China

Location

Investigational Site Number 1560005

Jinan, 250013, China

Location

Investigational Site Number 1560052

Jinhua, 321000, China

Location

Investigational Site Number 1560031

Jinzhou, 121000, China

Location

Investigational Site Number 1560022

Nanjing, 210029, China

Location

Investigational Site Number 1560014

Nanjing, China

Location

Investigational Site Number 1560043

Nanjing, China

Location

Investigational Site Number 1560041

Nanning, 530021, China

Location

Investigational Site Number 1560032

Qingdao, 266042, China

Location

Investigational Site Number 1560038

Qinhuangdao, China

Location

Investigational Site Number 1560013

Shanghai, 200072, China

Location

Investigational Site Number 1560007

Shanghai, 200240, China

Location

Investigational Site Number 1560004

Shanghai, 201700, China

Location

Investigational Site Number 1560029

Shanghai, China

Location

Investigational Site Number 1560003

Shenyang, 110022, China

Location

Investigational Site Number 1560054

Shenzhen, 518000, China

Location

Investigational Site Number 1560019

Suzhou, 215006, China

Location

Investigational Site Number 1560059

Suzhou, China

Location

Investigational Site Number 1560021

Tianjin, 300052, China

Location

Investigational Site Number 1560017

Tianjin, 300121, China

Location

Investigational Site Number 1560058

Ürümqi, 830000, China

Location

Investigational Site Number 1560018

Wuhan, 430014, China

Location

Investigational Site Number 1560008

Xi'an, 710061, China

Location

Investigational Site Number 1560055

Xi'an, China

Location

Investigational Site Number 1560051

Xingtai, 054031, China

Location

Investigational Site Number 1560030

Xining, 810007, China

Location

Investigational Site Number 1560040

Yanji, 133000, China

Location

Investigational Site Number 1560060

Yueyang, 414000, China

Location

Investigational Site Number 1560046

Yueyang, China

Location

Investigational Site Number 1560045

Zhengzhou, China

Location

Investigational Site Number 1560002

Zhenjiang, 212001, China

Location

Investigational Site Number 1560015

Zhuzhou, 412007, China

Location

Investigational Site Number 1560057

Zigong, 643002, China

Location

Investigational Site Number 4580001

Kelantan, 16150, Malaysia

Location

Investigational Site Number 4580005

Kuala Lumpur, 56000, Malaysia

Location

Investigational Site Number 4580003

Kuala Lumpur, 59100, Malaysia

Location

Investigational Site Number 4580006

Kuching, 93586, Malaysia

Location

Investigational Site Number 4580002

Putrajaya, Malaysia

Location

Investigational Site Number 4580004

Seremban, 70300, Malaysia

Location

Investigational Site Number 4100009

Ansan-si, 15355, South Korea

Location

Investigational Site Number 4100012

Busan, 49241, South Korea

Location

Investigational Site Number 4100010

Guri-Si, Gyeonggi-Do, 11923, South Korea

Location

Investigational Site Number 4100004

Gwangju, 61469, South Korea

Location

Investigational Site Number 4100003

Seongnam-si, 13620, South Korea

Location

Investigational Site Number 4100016

Seoul, 01832, South Korea

Location

Investigational Site Number 4100011

Seoul, 03181, South Korea

Location

Investigational Site Number 4100013

Seoul, 03722, South Korea

Location

Investigational Site Number 4100001

Seoul, 05278, South Korea

Location

Investigational Site Number 4100002

Seoul, 08308, South Korea

Location

Investigational Site Number 4100005

Wŏnju, 26426, South Korea

Location

Investigational Site Number 1580003

Taichung, 407, Taiwan

Location

Investigational Site Number 1580005

Tainan Hsien, 710, Taiwan

Location

Investigational Site Number 1580004

Taipei, 11031, Taiwan

Location

Related Publications (2)

• Yang W, Dong X, Li Q, Cheng Z, Yuan G, Liu M, Xiao J, Gu S, Niemoeller E, Chen L, Ping L, Souhami E; LixiLan-O-AP trial investigators. Efficacy and safety benefits of iGlarLixi versus insulin glargine 100 U/mL or lixisenatide in Asian Pacific people with suboptimally controlled type 2 diabetes on oral agents: The LixiLan-O-AP randomized controlled trial. Diabetes Obes Metab. 2022 Aug;24(8):1522-1533. doi: 10.1111/dom.14722. Epub 2022 May 12.

  PMID: 35441412 BACKGROUND

• 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.

  PMID: 36999231 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Insulin Glargine; lixisenatide; Metformin; Sodium-Glucose Transporter 2 Inhibitors

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Biguanides; Guanidines; Amidines; Organic Chemicals; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2019
• First Posted: January 9, 2019
• Study Start: February 15, 2019
• Primary Completion: March 1, 2021
• Study Completion: March 1, 2021
• Last Updated: July 19, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share

Locations

TW (3); CN (59); KR (11); MY (6)