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

Type 2 Diabetes Mellitus Clinical Trial

— Lixilan-O-AP  

Official title:

A Randomized, 24 Week, Active-controlled, Open-label, 3-arm, Parallel-group Multicenter Study Comparing the Efficacy and Safety of iGlarLixi to Insulin Glargine and Lixisenatide in Type 2 Diabetes Mellitus Patients Insufficiently Controlled With Oral Antidiabetic Drug(s)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03798054
• Other study ID #: EFC14943
• Secondary ID: U1111-1190-7669
• Status: Completed
• Phase: Phase 3
• Start date: February 15, 2019
• Est. completion date: March 1, 2021

Study information

• Verified date: April 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The maximum study duration per patient will be approximately 31 weeks: an up-to 6-week screening and run-in period (with an up-to 2-week screening phase and a 4-week run-in phase), followed by a 24-week randomized treatment period and a 3-day post-treatment safety follow up period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 878
• Est. completion date: March 1, 2021
• Est. primary completion date: March 1, 2021
• 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 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.

Exclusion criteria:

• 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.

• Use of oral or injectable glucose-lowering agents other than those stated in the inclusion criteria within 3 months 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.

• 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 (V1):

• 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 urine pregnancy test in female of childbearing potential.

• Patient who has a severe renal function impairment with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 or end-stage renal disease.

• 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).

• Use of SU, glinide, alpha-GI, DPP-4 inhibitor, and SGLT-2 inhibitor after start of run-in (from V2 [Week -4]).

• HbA1c at V4 (Week -1) : <7.0% or >10%.

• Fasting plasma glucose >250 mg/dL (13.9 mmol/L) at V4 (Week-1) (can be repeated once to confirm).

• Metformin maximal tolerated dose <1500 mg/day.

• Amylase and/or lipase >3 ULN at V4 (Week-1).

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
• Lixisenatide (AVE0010)
Pharmaceutical form: solution Route of administration: subcutaneous
• Metformin
Pharmaceutical form: tablet Route of administration: oral
• SGLT2 inhibitor
Pharmaceutical form:tablet Route of administration: oral

Locations

Country	Name	City	State
China	Investigational Site Number 1560001	Beijing
China	Investigational Site Number 1560006	Beijing
China	Investigational Site Number 1560049	Beijing
China	Investigational Site Number 1560039	Cangzhou
China	Investigational Site Number 1560009	Changchun
China	Investigational Site Number 1560027	Changchun
China	Investigational Site Number 1560016	Changsha
China	Investigational Site Number 1560053	Chengdu
China	Investigational Site Number 1560056	Chengdu
China	Investigational Site Number 1560010	Chenzhou
China	Investigational Site Number 1560037	Chongqing
China	Investigational Site Number 1560050	Chongqing
China	Investigational Site Number 1560044	Dongguan
China	Investigational Site Number 1560028	Guangzhou
China	Investigational Site Number 1560033	Guangzhou
China	Investigational Site Number 1560012	Handan
China	Investigational Site Number 1560023	Hangzhou
China	Investigational Site Number 1560035	Harbin
China	Investigational Site Number 1560036	Harbin
China	Investigational Site Number 1560011	Hengshui
China	Investigational Site Number 1560024	Hohhot
China	Investigational Site Number 1560047	Hohhot
China	Investigational Site Number 3440001	Hong Kong
China	Investigational Site Number 1560025	Huang Shi
China	Investigational Site Number 1560026	Huanggang
China	Investigational Site Number 1560048	Huizhou
China	Investigational Site Number 1560034	Huzhou
China	Investigational Site Number 1560005	Jinan
China	Investigational Site Number 1560052	Jinhua
China	Investigational Site Number 1560031	Jinzhou
China	Investigational Site Number 1560014	Nanjing
China	Investigational Site Number 1560022	Nanjing
China	Investigational Site Number 1560043	Nanjing
China	Investigational Site Number 1560041	Nanning
China	Investigational Site Number 1560032	Qingdao
China	Investigational Site Number 1560038	Qinhuangdao
China	Investigational Site Number 1560004	Shanghai
China	Investigational Site Number 1560007	Shanghai
China	Investigational Site Number 1560013	Shanghai
China	Investigational Site Number 1560029	Shanghai
China	Investigational Site Number 1560003	Shenyang
China	Investigational Site Number 1560054	Shenzhen
China	Investigational Site Number 1560019	Suzhou
China	Investigational Site Number 1560059	Suzhou
China	Investigational Site Number 1560017	Tianjin
China	Investigational Site Number 1560021	Tianjin
China	Investigational Site Number 1560058	Urumqi
China	Investigational Site Number 1560018	Wuhan
China	Investigational Site Number 1560008	Xi'An
China	Investigational Site Number 1560055	Xi'An
China	Investigational Site Number 1560051	Xingtai
China	Investigational Site Number 1560030	Xining
China	Investigational Site Number 1560040	Yanji
China	Investigational Site Number 1560046	Yueyang
China	Investigational Site Number 1560060	Yueyang
China	Investigational Site Number 1560045	Zhengzhou
China	Investigational Site Number 1560002	Zhenjiang
China	Investigational Site Number 1560015	Zhuzhou
China	Investigational Site Number 1560057	Zigong
Korea, Republic of	Investigational Site Number 4100009	Ansan-Si
Korea, Republic of	Investigational Site Number 4100012	Busan
Korea, Republic of	Investigational Site Number 4100010	Guri-Si, Gyeonggi-Do
Korea, Republic of	Investigational Site Number 4100004	Gwangju
Korea, Republic of	Investigational Site Number 4100003	Seongnam-Si
Korea, Republic of	Investigational Site Number 4100001	Seoul
Korea, Republic of	Investigational Site Number 4100002	Seoul
Korea, Republic of	Investigational Site Number 4100011	Seoul
Korea, Republic of	Investigational Site Number 4100013	Seoul
Korea, Republic of	Investigational Site Number 4100016	Seoul
Korea, Republic of	Investigational Site Number 4100005	Wonju
Malaysia	Investigational Site Number 4580001	Kelantan
Malaysia	Investigational Site Number 4580003	Kuala Lumpur
Malaysia	Investigational Site Number 4580005	Kuala Lumpur
Malaysia	Investigational Site Number 4580006	Kuching
Malaysia	Investigational Site Number 4580002	Putrajaya
Malaysia	Investigational Site Number 4580004	Seremban
Taiwan	Investigational Site Number 1580003	Taichung
Taiwan	Investigational Site Number 1580005	Tainan Hsien
Taiwan	Investigational Site Number 1580004	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

China,  Korea, Republic of,  Malaysia,  Taiwan, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c	Change in glycated hemoglobin (HbA1c) from baseline to Week 24	From Baseline to Week 24
Secondary	Change in postprandial plasma glucose (PPG)	Absolute change in 2-hour blood glucose excursion and PPG during meal test from baseline to Week 24 (for all patients in iGlarLixi or insulin glargine group and patients who receive morning injection in the lixisenatide group)	From Baseline to Week 24
Secondary	Change in fasting plasma glucose (FPG)	Absolute change in FPG from baseline to Week 24	From Baseline to Week 24
Secondary	Change in self-monitored plasma glucose (SMPG) profile	Absolute change in 7-point SMPG profiles from baseline to Week 24 (each time point and average daily value)	From Baseline to Week 24
Secondary	Patients with HbA1c <7.0%	Percentage of patients reaching HbA1c <7% at Week 24	At Week 24
Secondary	Patients with HbA1c = 6.5%	Percentage of patients reaching HbA1c = 6.5% at Week 24	At Week 24
Secondary	Change in body weight	Absolute change in body weight from baseline to Week 24	From Baseline to Week 24
Secondary	Patients with HbA1c <7.0% with no body weight gain	Percentage of patients reaching HbA1c <7% with no body weight gain at Week 24	At Week 24
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 24 and no documented (plasma glucose [PG] =70 mg/dL [3.9 mmol/L]) symptomatic hypoglycemia during the 24 week treatment period	At Week 24
Secondary	Confirmed hypoglycemia	Including severe hypoglycemia and episodes of hypoglycemia documented with PG =70 mg/dL (3.9 mmol/L) regardless of symptoms from baseline to Week 24	From Baseline to Week 24
Secondary	Adverse events (AEs)	Number of AEs, serious AEs, AEs of Special Interest, and AEs requiring specific monitoring from baseline to Week 24	From Baseline to Week 24
Secondary	Immunogenicity (antibody variables)	Anti-lixisenatide antibodies and anti-insulin antibodies (depending on the treatment group) from baseline to Week 24	From Baseline to Week 24