Clinical trial NCT02752828: Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination (LixiLan) to Insulin Glargine Alone 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 the Insulin Glargine/Lixisenatide Combination to Insulin Glargine on Top of OADs in Japanese Patients With Type 2 Diabetes Mellitus (T2DM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2016-04-27
Enrollment: 521
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 insulin glargine in glycated hemoglobin (HbA1c) change from baseline to Week 26 in patients with type 2 Diabetes.

Secondary Objective:

To compare the overall efficacy and safety of LixiLan to insulin glargine (with or without OADs) over a 26 Week treatment period in patients with type 2 Diabetes.

Detailed description: The maximum study duration per patient will be approximately 29 weeks: an up to 2-week screening period, a 26-week randomized open-label 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 (TZD), -Alpha-glucosidase-inhibitor (alpha-GI),Sodium glucose co-transporter 2 (SGLT2) inhibitor,Sulfonylurea (SU),Rapid-acting insulin secretagogue (Glinide),diphenyl-peptidase -4 inhibitor (DPP-4 inhibitor).
* Signed written informed consent.

Exclusion criteria:

* At the screening visit: Age \<20 years.
* At the screening visit: HbA1c \<7.5% or \>9.5%.
* At the screening visit: fasting plasma glucose (FPG) \>180 mg/dL (10.0 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 during the inclusion criteria in 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 time of screening:
* Amylase and/or lipase: \>3 times the upper limit of the normal (ULN) laboratory range,
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST): \>3 ULN,
* Calcitonin ≥20 pg/mL (5.9 pmol/L),
* Positive serum pregnancy test in female of childbearing potential.
* Contraindication to use of lixisenatide according to the local labeling. History of hypersensitivity to any Glucagon-Like Peptide-1 Receptor Agonists or to metacresol.
* Contraindication to use of insulin glargine according to 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/1.73 m\^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 2-hour postprandial glucose (PPG) during standardized meal test
timeFrame: Baseline, 26 weeks
measure: Change from baseline in 7 point self monitored plasma glucose (SMPG) profiles during standardized meal test
timeFrame: Baseline, 26 weeks
measure: Change from baseline in body weight
timeFrame: Baseline, 26 weeks
measure: Percentage of patients reaching HbA1c <7% with no body weight gain and with no documented (PG ≤70 mg/dL [3.9 mmol/L]) symptomatic hypoglycemia
timeFrame: 26 weeks
measure: Percentage of patients reaching HbA1c <7% at Week 26 with no documented (PG ≤70 mg/dL [3.9 mmol/L]) symptomatic hypoglycemia
timeFrame: 26 weeks
measure: Percentage of patients requiring a rescue therapy
timeFrame: 26 weeks
measure: Number of adverse events
timeFrame: 26 weeks
measure: Number of hypoglycemic events
timeFrame: 26 weeks
measure: Measurement of anti-lixisenatide antibodies from baseline
timeFrame: Baseline, 26 weeks
measure: Measurement of anti-insulin antibodies from baseline
timeFrame: Baseline, 26 weeks
Other outcomes:
Locations:
city: Adachi-Ku
country: Japan
facility: Investigational Site Number 392002
city: Annaka-Shi
country: Japan
facility: Investigational Site Number 392132
city: Arakawa-Ku
country: Japan
facility: Investigational Site Number 392009
city: Atsugi-Shi
country: Japan
facility: Investigational Site Number 392025
city: Chiba-Shi
country: Japan
facility: Investigational Site Number 392024
city: Chiba-Shi
country: Japan
facility: Investigational Site Number 392151
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: Chuo-Ku
country: Japan
facility: Investigational Site Number 392055
city: Chuo-Ku
country: Japan
facility: Investigational Site Number 392155
city: Fujimi-Shi
country: Japan
facility: Investigational Site Number 392008
city: Fujisawa-Shi
country: Japan
facility: Investigational Site Number 392143
city: Fukuoka-Shi
country: Japan
facility: Investigational Site Number 392054
city: Fukuoka-Shi
country: Japan
facility: Investigational Site Number 392094
city: Fukuoka-Shi
country: Japan
facility: Investigational Site Number 392147
city: Gifu-Shi
country: Japan
facility: Investigational Site Number 392100
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: Hamamatsu-Shi
country: Japan
facility: Investigational Site Number 392102
city: Hiki-Gun
country: Japan
facility: Investigational Site Number 392079
city: Hirosaki-Shi
country: Japan
facility: Investigational Site Number 392112
city: Hofu-Shi
country: Japan
facility: Investigational Site Number 392109
city: Iruma-Shi
country: Japan
facility: Investigational Site Number 392057
city: Ise-Shi
country: Japan
facility: Investigational Site Number 392022
city: Izumisano-Shi
country: Japan
facility: Investigational Site Number 392020
city: Kagoshima-Shi
country: Japan
facility: Investigational Site Number 392139
city: Kamogawa-Shi
country: Japan
facility: Investigational Site Number 392136
city: Kashiwa-Shi
country: Japan
facility: Investigational Site Number 392066
city: Kashiwara-Shi
country: Japan
facility: Investigational Site Number 392045
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: Kawasaki-Shi
country: Japan
facility: Investigational Site Number 392091
city: Kawasaki-Shi
country: Japan
facility: Investigational Site Number 392142
city: Kitaazumi-Gun
country: Japan
facility: Investigational Site Number 392133
city: Kitakyushu-Shi
country: Japan
facility: Investigational Site Number 392129
city: Kitakyusyu-Shi
country: Japan
facility: Investigational Site Number 392041
city: Kitakyusyu-Shi
country: Japan
facility: Investigational Site Number 392068
city: Kitamoto-Shi
country: Japan
facility: Investigational Site Number 392114
city: Kobe-Shi
country: Japan
facility: Investigational Site Number 392086
city: Koga-Shi
country: Japan
facility: Investigational Site Number 392044
city: Kokubunji-Shi
country: Japan
facility: Investigational Site Number 392119
city: Koriyama-Shi
country: Japan
facility: Investigational Site Number 392001
city: Kumamoto-Shi
country: Japan
facility: Investigational Site Number 392028
city: Kumamoto-Shi
country: Japan
facility: Investigational Site Number 392092
city: Kumamoto-Shi
country: Japan
facility: Investigational Site Number 392108
city: Kure-Shi
country: Japan
facility: Investigational Site Number 392075
city: Kurume-Shi
country: Japan
facility: Investigational Site Number 392032
city: Kushiro-Shi
country: Japan
facility: Investigational Site Number 392118
city: Kyoto-Shi
country: Japan
facility: Investigational Site Number 392107
city: Maebashi-Shi
country: Japan
facility: Investigational Site Number 392088
city: Matsumoto-Shi
country: Japan
facility: Investigational Site Number 392113
city: Minato-Ku
country: Japan
facility: Investigational Site Number 392122
city: Misato-Shi
country: Japan
facility: Investigational Site Number 392076
city: Mito-Shi
country: Japan
facility: Investigational Site Number 392042
city: Mito-Shi
country: Japan
facility: Investigational Site Number 392078
city: Nagano-Shi
country: Japan
facility: Investigational Site Number 392148
city: Nagoya-Shi
country: Japan
facility: Investigational Site Number 392026
city: Nagoya-Shi
country: Japan
facility: Investigational Site Number 392101
city: Nagoya-Shi
country: Japan
facility: Investigational Site Number 392128
city: Nagoya-Shi
country: Japan
facility: Investigational Site Number 392131
city: Nagoya-Shi
country: Japan
facility: Investigational Site Number 392134
city: Naka-Shi
country: Japan
facility: Investigational Site Number 392154
city: Niigata-Shi
country: Japan
facility: Investigational Site Number 392127
city: Niihama-Shi
country: Japan
facility: Investigational Site Number 392050
city: Ogawa-Machi, Hikigun
country: Japan
facility: Investigational Site Number 392115
city: Okayama-Shi
country: Japan
facility: Investigational Site Number 392071
city: Onga-Gun
country: Japan
facility: Investigational Site Number 392095
city: Osaka-Shi
country: Japan
facility: Investigational Site Number 392117
city: Osaka-Shi
country: Japan
facility: Investigational Site Number 392144
city: Oyama-Shi
country: Japan
facility: Investigational Site Number 392040
city: Saga-Shi
country: Japan
facility: Investigational Site Number 392084
city: Saijo-Shi
country: Japan
facility: Investigational Site Number 392069
city: Saitama-Shi
country: Japan
facility: Investigational Site Number 392030
city: Sanda-Shi
country: Japan
facility: Investigational Site Number 392074
city: Sapporo-Shi
country: Japan
facility: Investigational Site Number 392047
city: Sapporo-Shi
country: Japan
facility: Investigational Site Number 392089
city: Sapporo-Shi
country: Japan
facility: Investigational Site Number 392150
city: Sasebo-Shi
country: Japan
facility: Investigational Site Number 392097
city: Sendai-Shi
country: Japan
facility: Investigational Site Number 392004
city: Sendai-Shi
country: Japan
facility: Investigational Site Number 392103
city: Shimonoseki-Shi
country: Japan
facility: Investigational Site Number 392070
city: Shimotsuke-Shi
country: Japan
facility: Investigational Site Number 392034
city: Shinagawa-Ku
country: Japan
facility: Investigational Site Number 392110
city: Shinjuku-Ku
country: Japan
facility: Investigational Site Number 392021
city: Shinjuku-Ku
country: Japan
facility: Investigational Site Number 392098
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: Takamatsu-Shi
country: Japan
facility: Investigational Site Number 392146
city: Takatsuki-Shi
country: Japan
facility: Investigational Site Number 392051
city: Tokorozawa-Shi
country: Japan
facility: Investigational Site Number 392061
city: Tomakomai-Shi
country: Japan
facility: Investigational Site Number 392111
city: Toyonaka-Shi
country: Japan
facility: Investigational Site Number 392029
city: Tsu-Shi
country: Japan
facility: Investigational Site Number 392073
city: Ube-Shi
country: Japan
facility: Investigational Site Number 392063
city: Ube-Shi
country: Japan
facility: Investigational Site Number 392093
city: Yamato-Shi
country: Japan
facility: Investigational Site Number 392039
city: Yatsushiro-Shi
country: Japan
facility: Investigational Site Number 392067
city: Yokohama-Shi
country: Japan
facility: Investigational Site Number 392012
city: Yokohama-Shi
country: Japan
facility: Investigational Site Number 392126
city: Zentsuji-Shi
country: Japan
facility: Investigational Site Number 392035
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Terauchi Y, Nakama T, Spranger R, Amano A, Inoue T, Niemoeller E. Efficacy and safety of insulin glargine/lixisenatide fixed-ratio combination (iGlarLixi 1:1) in Japanese patients with type 2 diabetes mellitus inadequately controlled on oral antidiabetic drugs: A randomized, 26-week, open-label, multicentre study: The LixiLan JP-O2 randomized clinical trial. Diabetes Obes Metab. 2020 Sep;22 Suppl 4:14-23. doi: 10.1111/dom.14036.