Clinical trial NCT02752412: Efficacy and Safety of LixiLan Versus Insulin Glargine Alone Both With Metformin in Japanese With Type 2 Diabetes Mellitus Inadequately Controlled on Basal Insulin and Oral Antidiabetic Drugs
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 With Metformin in Japanese Patients With Type 2 Diabetes Mellitus Inadequately Controlled on Basal Insulin and Oral Antidiabetic Drugs
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: 513
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 mellitus.

Secondary Objective:

To compare overall efficacy and safety of LixiLan to insulin glargine over 26 weeks in patients with type 2 diabetes mellitus.

Detailed description: The maximum study duration per patient will be approximately 41 weeks: an up to 14-week screening period (consisting of an up to 2-week screening phase and a 12-week run-in phase), a 26-week randomized 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 (V1).
* Patient treated with a stable, once a day basal insulin regimen (ie, type of insulin and time/frequency of the injection), for at least 3 months before the screening visit.
* The total daily basal insulin dose should be stable (± 20%) and \<15 U/day for at least 1 month before the screening visit.
* Patient receiving 1 or 2 oral anti-diabetic drugs (OADs): the OAD dose(s) must be stable during the 3 months before the screening visit. The OADs can be 1 to 2 out of:
* Metformin;
* Sulfonylurea (SU);
* Glinide;
* Dipeptidyl-peptidase-4 (DPP-4) inhibitor;
* Sodium glucose co-transporter 2 (SGLT2) inhibitor;
* Alpha glucosidase inhibitor (alpha-GI).
* Signed written informed consent.

Exclusion criteria:

* Age \<20 years at screening visit.
* HbA1c at screening visit \<7.5% or \>9.5%.
* Fasting plasma glucose (FPG) \>180 mg/dL (10.0 mmol/L) at screening visit.
* 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 in the 3 months before screening visit.
* Previous use of insulin regimen other than basal insulin, eg, prandial or pre-mixed insulin.

Note: Short-term treatment (≤10 days) due to intercurrent illness including gestational diabetes is allowed at the discretion of the Investigator.

* Use of thiazolidinedione (TZD) within 6 months prior to screening visit.
* History of discontinuation of a previous treatment with a glucagon-like peptide-1(GLP-1) receptor agonist due to safety/ tolerability issues or lack of efficacy.
* Laboratory findings at the screening visit; including:
* 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.
* Any contraindication to metformin use according to local labeling.
* History of hypersensitivity to any GLP-1 receptor agonist or to metacresol.
* Contraindication to use of insulin glargine or lixisenatide according to local labeling. History of hypersensitivity to insulin glargine or to any of the excipients.
* 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 now been performed), pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, pancreatectomy, stomach/gastric surgery.
* Exclusion criteria for randomization at the end of the run-in phase:
* HbA1c \<7.5% or \>9.5% at visit 6 (Week -1).
* Mean fasting self monitored plasma glucose (SMPG) \>160 mg/dL (8.9 mmol/L), calculated from all available (minimum of 4 self-measurements) values during the 7 days prior to randomization.

Note:fasting SMPG on the day of randomization can be included if assessed before randomization.

* Average insulin glargine daily dose ≥15 U/day or \<5U/day calculated for the last 3 days before Visit 7.
* Metformin total daily dose \<750 mg/day.
* Amylase and/or lipase \>3 ULN at Visit 6 (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 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 plasma glucose (PPG) during standardized meal test
timeFrame: Baseline, 26 weeks
measure: Change from baseline in blood glucose excursion during standardized meal test
timeFrame: Baseline, 26 weeks
measure: Change from baseline in 7-point self-monitoring plasma glucose (SMPG) profiles (each time point and average daily value)
timeFrame: Baseline, 26 weeks
measure: Change from baseline in body weight
timeFrame: Baseline, 26 weeks
measure: Change from baseline in FPG
timeFrame: Baseline, 26 weeks
measure: Change from baseline in daily dose of insulin glargine
timeFrame: Baseline, 26 weeks
measure: Percentage of patients reaching HbA1c <7% with no body weight gain
timeFrame: 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% 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 hypoglycemic events
timeFrame: 26 weeks
measure: Number of adverse 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: Asahikawa-Shi
country: Japan
facility: Investigational Site Number 392152
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: 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 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: Hamamatsu-Shi
country: Japan
facility: Investigational Site Number 392048
city: Hamamatsu-Shi
country: Japan
facility: Investigational Site Number 392102
city: Higashiosaka-Shi
country: Japan
facility: Investigational Site Number 392123
city: Higashiosaka-Shi
country: Japan
facility: Investigational Site Number 392135
city: Hiki-Gun
country: Japan
facility: Investigational Site Number 392079
city: Himeji-Shi
country: Japan
facility: Investigational Site Number 392141
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: Kamakura-Shi
country: Japan
facility: Investigational Site Number 392036
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: Kasugai-Shi
country: Japan
facility: Investigational Site Number 392149
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: Kawaguchi-Shi
country: Japan
facility: Investigational Site Number 392090
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 392142
city: Kisarazu-Shi
country: Japan
facility: Investigational Site Number 392010
city: Kisarazu-Shi
country: Japan
facility: Investigational Site Number 392016
city: Kitakyushu-Shi
country: Japan
facility: Investigational Site Number 392031
city: Kitakyushu-Shi
country: Japan
facility: Investigational Site Number 392068
city: Kitakyusyu-Shi
country: Japan
facility: Investigational Site Number 392041
city: Kobe-Shi
country: Japan
facility: Investigational Site Number 392086
city: Koga-Shi
country: Japan
facility: Investigational Site Number 392044
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: Kumamoto-Shi
country: Japan
facility: Investigational Site Number 392116
city: Kushiro-Shi
country: Japan
facility: Investigational Site Number 392099
city: Kyoto-Shi
country: Japan
facility: Investigational Site Number 392049
city: Kyoto-Shi
country: Japan
facility: Investigational Site Number 392107
city: Maebashi-Shi
country: Japan
facility: Investigational Site Number 392088
city: Maebashi-Shi
country: Japan
facility: Investigational Site Number 392158
city: Matsuyama-Shi
country: Japan
facility: Investigational Site Number 392121
city: Minato-Ku
country: Japan
facility: Investigational Site Number 392122
city: Misato-Shi
country: Japan
facility: Investigational Site Number 392076
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 392043
city: Mito-Shi
country: Japan
facility: Investigational Site Number 392078
city: Miyazaki-Shi
country: Japan
facility: Investigational Site Number 392046
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: Nagoya-Shi
country: Japan
facility: Investigational Site Number 392137
city: Nagoya-Shi
country: Japan
facility: Investigational Site Number 392140
city: Naka-Shi
country: Japan
facility: Investigational Site Number 392154
city: Niihama-Shi
country: Japan
facility: Investigational Site Number 392050
city: Obihiro-Shi
country: Japan
facility: Investigational Site Number 392159
city: Ogaki-Shi
country: Japan
facility: Investigational Site Number 392145
city: Oita-Shi
country: Japan
facility: Investigational Site Number 392153
city: Okawa-Shi
country: Japan
facility: Investigational Site Number 392005
city: Okayama-Shi
country: Japan
facility: Investigational Site Number 392071
city: Okayama-Shi
country: Japan
facility: Investigational Site Number 392080
city: Onga-Gun
country: Japan
facility: Investigational Site Number 392095
city: Osaka-Shi
country: Japan
facility: Investigational Site Number 392105
city: Osaka-Shi
country: Japan
facility: Investigational Site Number 392117
city: Osaka-Shi
country: Japan
facility: Investigational Site Number 392144
city: Osaki-Shi
country: Japan
facility: Investigational Site Number 392125
city: Ota-Ku
country: Japan
facility: Investigational Site Number 392120
city: Ota-Shi
country: Japan
facility: Investigational Site Number 392157
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: Saitama-Shi
country: Japan
facility: Investigational Site Number 392058
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 392106
city: Sasebo-Shi
country: Japan
facility: Investigational Site Number 392097
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: 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: Shiogama-Shi
country: Japan
facility: Investigational Site Number 392104
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: Takatsuki-Shi
country: Japan
facility: Investigational Site Number 392156
city: Tokorozawa-Shi
country: Japan
facility: Investigational Site Number 392061
city: Tomakomai-Shi
country: Japan
facility: Investigational Site Number 392111
city: Tsu-Shi
country: Japan
facility: Investigational Site Number 392073
city: Ube-Shi
country: Japan
facility: Investigational Site Number 392063
city: Ushiku-Shi
country: Japan
facility: Investigational Site Number 392124
city: Yatsushiro-Shi
country: Japan
facility: Investigational Site Number 392067
city: Yokohama-Shi
country: Japan
facility: Investigational Site Number 392085
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: Kaneto H, Takami A, Spranger R, Amano A, Watanabe D, Niemoeller E. Efficacy and safety of insulin glargine/lixisenatide fixed-ratio combination (iGlarLixi) in Japanese patients with type 2 diabetes mellitus inadequately controlled on basal insulin and oral antidiabetic drugs: The LixiLan JP-L randomized clinical trial. Diabetes Obes Metab. 2020 Sep;22 Suppl 4:3-13. doi: 10.1111/dom.14005.