Clinical trial NCT03798054: Evaluation of Insulin Glargine/Lixisenatide Fixed Ratio Combination in Patients With Type 2 Diabetes Insufficiently Controlled With Oral Antidiabetic Drug(s)
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)
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: 878
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 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in HbA1c
timeFrame: From Baseline to Week 24
Secondary outcomes:
measure: Change in postprandial plasma glucose (PPG)
timeFrame: From Baseline to Week 24
measure: Change in fasting plasma glucose (FPG)
timeFrame: From Baseline to Week 24
measure: Change in self-monitored plasma glucose (SMPG) profile
timeFrame: From Baseline to Week 24
measure: Patients with HbA1c <7.0%
timeFrame: At Week 24
measure: Patients with HbA1c ≤ 6.5%
timeFrame: At Week 24
measure: Change in body weight
timeFrame: From Baseline to Week 24
measure: Patients with HbA1c <7.0% with no body weight gain
timeFrame: At Week 24
measure: Patients with HbA1c <7.0% with no body weight gain and no documented symptomatic hypoglycemia
timeFrame: At Week 24
measure: Confirmed hypoglycemia
timeFrame: From Baseline to Week 24
measure: Adverse events (AEs)
timeFrame: From Baseline to Week 24
measure: Immunogenicity (antibody variables)
timeFrame: From Baseline to Week 24
Other outcomes:
Locations:
city: Beijing
country: China
facility: Investigational Site Number 1560001
city: Beijing
country: China
facility: Investigational Site Number 1560006
city: Beijing
country: China
facility: Investigational Site Number 1560049
city: Cangzhou
country: China
facility: Investigational Site Number 1560039
city: Changchun
country: China
facility: Investigational Site Number 1560009
city: Changchun
country: China
facility: Investigational Site Number 1560027
city: Changsha
country: China
facility: Investigational Site Number 1560016
city: Chengdu
country: China
facility: Investigational Site Number 1560053
city: Chengdu
country: China
facility: Investigational Site Number 1560056
city: Chenzhou
country: China
facility: Investigational Site Number 1560010
city: Chongqing
country: China
facility: Investigational Site Number 1560037
city: Chongqing
country: China
facility: Investigational Site Number 1560050
city: Dongguan
country: China
facility: Investigational Site Number 1560044
city: Guangzhou
country: China
facility: Investigational Site Number 1560033
city: Guangzhou
country: China
facility: Investigational Site Number 1560028
city: Handan
country: China
facility: Investigational Site Number 1560012
city: Hangzhou
country: China
facility: Investigational Site Number 1560023
city: Harbin
country: China
facility: Investigational Site Number 1560035
city: Harbin
country: China
facility: Investigational Site Number 1560036
city: Hengshui
country: China
facility: Investigational Site Number 1560011
city: Hohhot
country: China
facility: Investigational Site Number 1560024
city: Hohhot
country: China
facility: Investigational Site Number 1560047
city: Hong Kong
country: China
facility: Investigational Site Number 3440001
city: Huang Shi
country: China
facility: Investigational Site Number 1560025
city: Huanggang
country: China
facility: Investigational Site Number 1560026
city: Huizhou
country: China
facility: Investigational Site Number 1560048
city: Huzhou
country: China
facility: Investigational Site Number 1560034
city: Jinan
country: China
facility: Investigational Site Number 1560005
city: Jinhua
country: China
facility: Investigational Site Number 1560052
city: Jinzhou
country: China
facility: Investigational Site Number 1560031
city: Nanjing
country: China
facility: Investigational Site Number 1560022
city: Nanjing
country: China
facility: Investigational Site Number 1560014
city: Nanjing
country: China
facility: Investigational Site Number 1560043
city: Nanning
country: China
facility: Investigational Site Number 1560041
city: Qingdao
country: China
facility: Investigational Site Number 1560032
city: Qinhuangdao
country: China
facility: Investigational Site Number 1560038
city: Shanghai
country: China
facility: Investigational Site Number 1560013
city: Shanghai
country: China
facility: Investigational Site Number 1560007
city: Shanghai
country: China
facility: Investigational Site Number 1560004
city: Shanghai
country: China
facility: Investigational Site Number 1560029
city: Shenyang
country: China
facility: Investigational Site Number 1560003
city: Shenzhen
country: China
facility: Investigational Site Number 1560054
city: Suzhou
country: China
facility: Investigational Site Number 1560019
city: Suzhou
country: China
facility: Investigational Site Number 1560059
city: Tianjin
country: China
facility: Investigational Site Number 1560021
city: Tianjin
country: China
facility: Investigational Site Number 1560017
city: Urumqi
country: China
facility: Investigational Site Number 1560058
city: Wuhan
country: China
facility: Investigational Site Number 1560018
city: Xi'An
country: China
facility: Investigational Site Number 1560008
city: Xi'An
country: China
facility: Investigational Site Number 1560055
city: Xingtai
country: China
facility: Investigational Site Number 1560051
city: Xining
country: China
facility: Investigational Site Number 1560030
city: Yanji
country: China
facility: Investigational Site Number 1560040
city: Yueyang
country: China
facility: Investigational Site Number 1560060
city: Yueyang
country: China
facility: Investigational Site Number 1560046
city: Zhengzhou
country: China
facility: Investigational Site Number 1560045
city: Zhenjiang
country: China
facility: Investigational Site Number 1560002
city: Zhuzhou
country: China
facility: Investigational Site Number 1560015
city: Zigong
country: China
facility: Investigational Site Number 1560057
city: Ansan-Si
country: Korea, Republic of
facility: Investigational Site Number 4100009
city: Busan
country: Korea, Republic of
facility: Investigational Site Number 4100012
city: Guri-Si, Gyeonggi-Do
country: Korea, Republic of
facility: Investigational Site Number 4100010
city: Gwangju
country: Korea, Republic of
facility: Investigational Site Number 4100004
city: Seongnam-Si
country: Korea, Republic of
facility: Investigational Site Number 4100003
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 4100016
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 4100011
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 4100013
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 4100001
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 4100002
city: Wonju
country: Korea, Republic of
facility: Investigational Site Number 4100005
city: Kelantan
country: Malaysia
facility: Investigational Site Number 4580001
city: Kuala Lumpur
country: Malaysia
facility: Investigational Site Number 4580005
city: Kuala Lumpur
country: Malaysia
facility: Investigational Site Number 4580003
city: Kuching
country: Malaysia
facility: Investigational Site Number 4580006
city: Putrajaya
country: Malaysia
facility: Investigational Site Number 4580002
city: Seremban
country: Malaysia
facility: Investigational Site Number 4580004
city: Taichung
country: Taiwan
facility: Investigational Site Number 1580003
city: Tainan Hsien
country: Taiwan
facility: Investigational Site Number 1580005
city: Taipei
country: Taiwan
facility: Investigational Site Number 1580004
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.