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

Type 2 Diabetes Mellitus Clinical Trial

— LIXILAN JP-L  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02752412
• Other study ID #: EFC14113
• Secondary ID: U1111-1176-8378
• Status: Completed
• Phase: Phase 3
• Start date: May 17, 2016
• Est. completion date: October 4, 2018

Study information

• Verified date: October 2018
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 513
• Est. completion date: October 4, 2018
• Est. primary completion date: October 4, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

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 U100 (HOE901)
Pharmaceutical form: solution Route of administration: subcutaneous
• Metformin
Pharmaceutical form: tablet Route of administration: oral

Locations

Country	Name	City	State
Japan	Investigational Site Number 392002	Adachi-Ku
Japan	Investigational Site Number 392132	Annaka-Shi
Japan	Investigational Site Number 392009	Arakawa-Ku
Japan	Investigational Site Number 392152	Asahikawa-Shi
Japan	Investigational Site Number 392025	Atsugi-Shi
Japan	Investigational Site Number 392024	Chiba-Shi
Japan	Investigational Site Number 392151	Chiba-Shi
Japan	Investigational Site Number 392011	Chigasaki-Shi
Japan	Investigational Site Number 392013	Chiyoda-Ku
Japan	Investigational Site Number 392052	Chiyoda-Ku
Japan	Investigational Site Number 392003	Chuo-Ku
Japan	Investigational Site Number 392017	Chuo-Ku
Japan	Investigational Site Number 392055	Chuo-Ku
Japan	Investigational Site Number 392008	Fujimi-Shi
Japan	Investigational Site Number 392143	Fujisawa-Shi
Japan	Investigational Site Number 392094	Fukuoka-Shi
Japan	Investigational Site Number 392147	Fukuoka-Shi
Japan	Investigational Site Number 392100	Gifu-Shi
Japan	Investigational Site Number 392059	Hachioji-Shi
Japan	Investigational Site Number 392048	Hamamatsu-Shi
Japan	Investigational Site Number 392102	Hamamatsu-Shi
Japan	Investigational Site Number 392123	Higashiosaka-Shi
Japan	Investigational Site Number 392135	Higashiosaka-Shi
Japan	Investigational Site Number 392079	Hiki-Gun
Japan	Investigational Site Number 392141	Himeji-Shi
Japan	Investigational Site Number 392057	Iruma-Shi
Japan	Investigational Site Number 392022	Ise-Shi
Japan	Investigational Site Number 392020	Izumisano-Shi
Japan	Investigational Site Number 392036	Kamakura-Shi
Japan	Investigational Site Number 392136	Kamogawa-Shi
Japan	Investigational Site Number 392066	Kashiwa-Shi
Japan	Investigational Site Number 392045	Kashiwara-Shi
Japan	Investigational Site Number 392006	Kasugai-Shi
Japan	Investigational Site Number 392149	Kasugai-Shi
Japan	Investigational Site Number 392053	Kawagoe-Shi
Japan	Investigational Site Number 392065	Kawagoe-Shi
Japan	Investigational Site Number 392007	Kawaguchi-Shi
Japan	Investigational Site Number 392062	Kawaguchi-Shi
Japan	Investigational Site Number 392090	Kawaguchi-Shi
Japan	Investigational Site Number 392077	Kawasaki-Shi
Japan	Investigational Site Number 392082	Kawasaki-Shi
Japan	Investigational Site Number 392142	Kawasaki-Shi
Japan	Investigational Site Number 392010	Kisarazu-Shi
Japan	Investigational Site Number 392016	Kisarazu-Shi
Japan	Investigational Site Number 392031	Kitakyushu-Shi
Japan	Investigational Site Number 392068	Kitakyushu-Shi
Japan	Investigational Site Number 392041	Kitakyusyu-Shi
Japan	Investigational Site Number 392086	Kobe-Shi
Japan	Investigational Site Number 392044	Koga-Shi
Japan	Investigational Site Number 392001	Koriyama-Shi
Japan	Investigational Site Number 392028	Kumamoto-Shi
Japan	Investigational Site Number 392092	Kumamoto-Shi
Japan	Investigational Site Number 392108	Kumamoto-Shi
Japan	Investigational Site Number 392116	Kumamoto-Shi
Japan	Investigational Site Number 392099	Kushiro-Shi
Japan	Investigational Site Number 392049	Kyoto-Shi
Japan	Investigational Site Number 392107	Kyoto-Shi
Japan	Investigational Site Number 392088	Maebashi-Shi
Japan	Investigational Site Number 392158	Maebashi-Shi
Japan	Investigational Site Number 392121	Matsuyama-Shi
Japan	Investigational Site Number 392122	Minato-Ku
Japan	Investigational Site Number 392076	Misato-Shi
Japan	Investigational Site Number 392014	Mitaka-Shi
Japan	Investigational Site Number 392042	Mito-Shi
Japan	Investigational Site Number 392043	Mito-Shi
Japan	Investigational Site Number 392078	Mito-Shi
Japan	Investigational Site Number 392046	Miyazaki-Shi
Japan	Investigational Site Number 392026	Nagoya-Shi
Japan	Investigational Site Number 392101	Nagoya-Shi
Japan	Investigational Site Number 392128	Nagoya-Shi
Japan	Investigational Site Number 392131	Nagoya-Shi
Japan	Investigational Site Number 392134	Nagoya-Shi
Japan	Investigational Site Number 392137	Nagoya-Shi
Japan	Investigational Site Number 392140	Nagoya-Shi
Japan	Investigational Site Number 392154	Naka-Shi
Japan	Investigational Site Number 392050	Niihama-Shi
Japan	Investigational Site Number 392159	Obihiro-Shi
Japan	Investigational Site Number 392145	Ogaki-Shi
Japan	Investigational Site Number 392153	Oita-Shi
Japan	Investigational Site Number 392005	Okawa-Shi
Japan	Investigational Site Number 392071	Okayama-Shi
Japan	Investigational Site Number 392080	Okayama-Shi
Japan	Investigational Site Number 392095	Onga-Gun
Japan	Investigational Site Number 392105	Osaka-Shi
Japan	Investigational Site Number 392117	Osaka-Shi
Japan	Investigational Site Number 392144	Osaka-Shi
Japan	Investigational Site Number 392125	Osaki-Shi
Japan	Investigational Site Number 392120	Ota-Ku
Japan	Investigational Site Number 392157	Ota-Shi
Japan	Investigational Site Number 392040	Oyama-Shi
Japan	Investigational Site Number 392038	Sagamihara-Shi
Japan	Investigational Site Number 392069	Saijo-Shi
Japan	Investigational Site Number 392030	Saitama-Shi
Japan	Investigational Site Number 392058	Saitama-Shi
Japan	Investigational Site Number 392074	Sanda-Shi
Japan	Investigational Site Number 392047	Sapporo-Shi
Japan	Investigational Site Number 392106	Sapporo-Shi
Japan	Investigational Site Number 392097	Sasebo-Shi
Japan	Investigational Site Number 392015	Satsumasendai-Shi
Japan	Investigational Site Number 392004	Sendai-Shi
Japan	Investigational Site Number 392034	Shimotsuke-Shi
Japan	Investigational Site Number 392110	Shinagawa-Ku
Japan	Investigational Site Number 392021	Shinjuku-Ku
Japan	Investigational Site Number 392098	Shinjuku-Ku
Japan	Investigational Site Number 392104	Shiogama-Shi
Japan	Investigational Site Number 392037	Shizuoka-Shi
Japan	Investigational Site Number 392081	Shizuoka-Shi
Japan	Investigational Site Number 392019	Shobara-Shi
Japan	Investigational Site Number 392018	Shunan-Shi
Japan	Investigational Site Number 392027	Suita-Shi
Japan	Investigational Site Number 392056	Taito-Ku
Japan	Investigational Site Number 392051	Takatsuki-Shi
Japan	Investigational Site Number 392156	Takatsuki-Shi
Japan	Investigational Site Number 392061	Tokorozawa-Shi
Japan	Investigational Site Number 392111	Tomakomai-Shi
Japan	Investigational Site Number 392073	Tsu-Shi
Japan	Investigational Site Number 392063	Ube-Shi
Japan	Investigational Site Number 392124	Ushiku-Shi
Japan	Investigational Site Number 392067	Yatsushiro-Shi
Japan	Investigational Site Number 392085	Yokohama-Shi
Japan	Investigational Site Number 392126	Yokohama-Shi
Japan	Investigational Site Number 392035	Zentsuji-Shi

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

Japan, 

References & Publications (1)

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 ora — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in HbA1c		Baseline, 26 weeks
Secondary	Percentage of patients reaching HbA1c <7% or =6.5%		26 weeks
Secondary	Change from baseline in 2-hour postprandial plasma glucose (PPG) during standardized meal test		Baseline, 26 weeks
Secondary	Change from baseline in blood glucose excursion during standardized meal test		Baseline, 26 weeks
Secondary	Change from baseline in 7-point self-monitoring plasma glucose (SMPG) profiles (each time point and average daily value)		Baseline, 26 weeks
Secondary	Change from baseline in body weight		Baseline, 26 weeks
Secondary	Change from baseline in FPG		Baseline, 26 weeks
Secondary	Change from baseline in daily dose of insulin glargine		Baseline, 26 weeks
Secondary	Percentage of patients reaching HbA1c <7% with no body weight gain		26 weeks
Secondary	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		26 weeks
Secondary	Percentage of patients reaching HbA1c <7% with no documented (PG =70 mg/dL [3.9 mmol/L]) symptomatic hypoglycemia		26 weeks
Secondary	Percentage of patients requiring a rescue therapy		26 weeks
Secondary	Number of hypoglycemic events		26 weeks
Secondary	Number of adverse events		26 weeks
Secondary	Measurement of anti-lixisenatide antibodies from baseline		Baseline, 26 weeks
Secondary	Measurement of anti-insulin antibodies from baseline		Baseline, 26 weeks