Clinical trial NCT02749890: Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination (LixiLan) to Lixisenatide on Top of Oral Anti-diabetic Drugs (OADs) With Type 2 Diabetes in Japan
Official title: A Randomized, Active-controlled, Open Label, 2-treatment Arm, and Multicenter Study Comparing the Efficacy and Safety of Insulin Glargine/Lixisenatide Combination to Lixisenatide on Top of OADs in Japanese Patients With Type 2 DM With an Extension Period
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2016-04-25
Enrollment: 321
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To compare LixiLan to lixisenatide in glycated hemoglobin (HbA1c) change from baseline to Week 26 in patients with type 2 diabetes mellitus.

Secondary Objective:

To compare the overall efficacy and safety of LixiLan to lixisenatide (with or without OADs) over a 52 week treatment period in patients with type 2 diabetes mellitus.

Detailed description: Approximately 55 weeks: an up-to 2-week screening period, a 26-week randomized open-label treatment period, a 26-week safety extension treatment period and a 3-day post-treatment safety follow up period.

Eligibility criteria: Inclusion criteria :

* Patient with type 2 diabetes mellitus (T2DM) diagnosed for at least 1 year before the screening visit, receiving 1 or 2 OADs that can be biguanide, thiazolidinedione, alpha-glucosidase-inhibitor, sodium glucose co-transporter 2 inhibitor; sulfonylurea, rapid-acting insulin secretagogue, or dipeptidyl-peptidase-4 inhibitor.
* Signed written informed consent.

Exclusion criteria:

* At the screening visit: age \<20 years.
* At the screening visit: HbA1c \<7.5% or \>10%.
* At the screening visit: fasting plasma glucose (FPG) \>250 mg/dL (13.8 mmol/L).
* Pregnancy or lactation, women of childbearing potential with no effective contraceptive method.
* Use of oral or injectable glucose-lowering agents other than those stated in the inclusion criteria during the 3 months before the screening visit.
* Previous treatment with insulin (except for short-term treatment due to intercurrent illness including gestational diabetes at the discretion of the trial physician).
* Laboratory findings at the screening visit, including:
* Amylase and/or lipase \>3 times the upper limit of the normal laboratory range (ULN),
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 ULN,
* Calcitonin ≥20 pg/mL (5.9 pmol/L),
* Positive serum pregnancy test.
* Contraindication to use of lixisenatide according to the local labeling. History of hypersensitivity to any glucagon-like peptide-1 receptor agonist (GLP-1RA) or to metacresol.
* Contraindication to use of insulin glargine according to the local labeling. History of hypersensitivity to insulin glargine or to any of the excipients.
* Patient who has a severe renal function impairment with estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73m\^2 or end-stage renal disease for patient not treated with metformin.
* Personal or immediate family history of medullary thyroid cancer (MTC) or genetic condition that predisposes to MTC (eg, multiple endocrine neoplasia syndromes).
* History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy has been performed), pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, pancreatectomy, stomach/gastric surgery.

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 from baseline in HbA1c
timeFrame: Baseline, 26 weeks
Secondary outcomes:
measure: Percentage of patients reaching HbA1c <7% or ≤6.5%
timeFrame: 26 weeks
measure: Change from baseline in fasting plasma glucose
timeFrame: Baseline, 26 weeks
measure: Change in from baseline in 7 point self-monitored plasma profiles
timeFrame: Baseline, 26 weeks
measure: Percentage of patients reaching HbA1c <7% with no body weight gain
timeFrame: 26 weeks
measure: Change from baseline in body weight
timeFrame: Baseline, 26 weeks
measure: Percentage of patients requiring a rescue therapy
timeFrame: 26 weeks
measure: Change in daily dose of insulin glargine for the combination group
timeFrame: Day 1, 26 weeks
measure: Number of hypoglycemic events
timeFrame: 26 weeks, 52 weeks
measure: Number of adverse events
timeFrame: 26 weeks, 52 weeks
measure: Measurement of anti-lixisenatide antibodies from baseline
timeFrame: Baseline, 26 weeks, 52 weeks
measure: Measurement of anti-insulin antibodies from baseline
timeFrame: Baseline, 26 weeks, 52 weeks
Other outcomes:
Locations:
city: Adachi-Ku
country: Japan
facility: Investigational Site Number 392002
city: Arakawa-Ku
country: Japan
facility: Investigational Site Number 392009
city: Atsugi-Shi
country: Japan
facility: Investigational Site Number 392025
city: Bunkyo-Ku
country: Japan
facility: Investigational Site Number 392060
city: Chiba-Shi
country: Japan
facility: Investigational Site Number 392024
city: Chigasaki-Shi
country: Japan
facility: Investigational Site Number 392011
city: Chiyoda-Ku
country: Japan
facility: Investigational Site Number 392013
city: Chiyoda-Ku
country: Japan
facility: Investigational Site Number 392052
city: Chuo-Ku
country: Japan
facility: Investigational Site Number 392003
city: Chuo-Ku
country: Japan
facility: Investigational Site Number 392017
city: Fujimi-Shi
country: Japan
facility: Investigational Site Number 392008
city: Fukuoka-Shi
country: Japan
facility: Investigational Site Number 392054
city: Fukuoka-Shi
country: Japan
facility: Investigational Site Number 392094
city: Hachioji-Shi
country: Japan
facility: Investigational Site Number 392059
city: Hakodate-Shi
country: Japan
facility: Investigational Site Number 392083
city: Hamamatsu-Shi
country: Japan
facility: Investigational Site Number 392048
city: Hiki-Gun
country: Japan
facility: Investigational Site Number 392079
city: Iruma-Shi
country: Japan
facility: Investigational Site Number 392057
city: Ise-Shi
country: Japan
facility: Investigational Site Number 392022
city: Isehara-Shi
country: Japan
facility: Investigational Site Number 392023
city: Izumisano-Shi
country: Japan
facility: Investigational Site Number 392020
city: Kashiwa-Shi
country: Japan
facility: Investigational Site Number 392066
city: Kasugai-Shi
country: Japan
facility: Investigational Site Number 392006
city: Kawagoe-Shi
country: Japan
facility: Investigational Site Number 392053
city: Kawagoe-Shi
country: Japan
facility: Investigational Site Number 392065
city: Kawaguchi-Shi
country: Japan
facility: Investigational Site Number 392007
city: Kawaguchi-Shi
country: Japan
facility: Investigational Site Number 392062
city: Kawasaki-Shi
country: Japan
facility: Investigational Site Number 392077
city: Kawasaki-Shi
country: Japan
facility: Investigational Site Number 392082
city: Kitakyushu-Shi
country: Japan
facility: Investigational Site Number 392031
city: Kitakyusyu-Shi
country: Japan
facility: Investigational Site Number 392041
city: Kitakyusyu-Shi
country: Japan
facility: Investigational Site Number 392068
city: Koga-Shi
country: Japan
facility: Investigational Site Number 392044
city: Koriyama-Shi
country: Japan
facility: Investigational Site Number 392001
city: Kurume-Shi
country: Japan
facility: Investigational Site Number 392032
city: Maebashi-Shi
country: Japan
facility: Investigational Site Number 392088
city: Mitaka-Shi
country: Japan
facility: Investigational Site Number 392014
city: Mito-Shi
country: Japan
facility: Investigational Site Number 392042
city: Mito-Shi
country: Japan
facility: Investigational Site Number 392078
city: Nagoya-Shi
country: Japan
facility: Investigational Site Number 392026
city: Okayama-Shi
country: Japan
facility: Investigational Site Number 392080
city: Oyama-Shi
country: Japan
facility: Investigational Site Number 392040
city: Sagamihara-Shi
country: Japan
facility: Investigational Site Number 392038
city: Saijo-Shi
country: Japan
facility: Investigational Site Number 392069
city: Saitama-Shi
country: Japan
facility: Investigational Site Number 392030
city: Sapporo-Shi
country: Japan
facility: Investigational Site Number 392047
city: Satsumasendai-Shi
country: Japan
facility: Investigational Site Number 392015
city: Sendai-Shi
country: Japan
facility: Investigational Site Number 392004
city: Shimotsuke-Shi
country: Japan
facility: Investigational Site Number 392034
city: Shizuoka-Shi
country: Japan
facility: Investigational Site Number 392037
city: Shizuoka-Shi
country: Japan
facility: Investigational Site Number 392081
city: Shobara-Shi
country: Japan
facility: Investigational Site Number 392019
city: Shunan-Shi
country: Japan
facility: Investigational Site Number 392018
city: Suita-Shi
country: Japan
facility: Investigational Site Number 392027
city: Taito-Ku
country: Japan
facility: Investigational Site Number 392056
city: Takatsuki-Shi
country: Japan
facility: Investigational Site Number 392051
city: Tokorozawa-Shi
country: Japan
facility: Investigational Site Number 392061
city: Toyonaka-Shi
country: Japan
facility: Investigational Site Number 392029
city: Ube-Shi
country: Japan
facility: Investigational Site Number 392093
city: Yatsushiro-Shi
country: Japan
facility: Investigational Site Number 392067
city: Zentsuji-Shi
country: Japan
facility: Investigational Site Number 392035
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Watada H, Takami A, Spranger R, Amano A, Hashimoto Y, Niemoeller E. Efficacy and Safety of 1:1 Fixed-Ratio Combination of Insulin Glargine and Lixisenatide Versus Lixisenatide in Japanese Patients With Type 2 Diabetes Inadequately Controlled on Oral Antidiabetic Drugs: The LixiLan JP-O1 Randomized Clinical Trial. Diabetes Care. 2020 Jun;43(6):1249-1257. doi: 10.2337/dc19-2452. Epub 2020 Apr 15.