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

NCT ID: NCT02752412

Last Updated: 2020-06-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 513 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-17
• Study Completion Date: 2018-10-04

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.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LixiLan

LixiLan (insulin glargine/lixisenatide fixed ratio combination) is injected subcutaneously (under the skin) once daily. Dose is individually adjusted.

Metformin will be continued.

Group Type: EXPERIMENTAL

Insulin glargine/Lixisenatide (HOE901/AVE0010)

Intervention Type: DRUG

Pharmaceutical form: solution

Route of administration: subcutaneous

Metformin

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

insulin glargine

Insulin glargine U100 (Lantus) will be injected subcutaneously (under skin) once daily. Dose will be individually adjusted.

Metformin will be continued.

Group Type: ACTIVE_COMPARATOR

Insulin glargine U100 (HOE901)

Intervention Type: DRUG

Pharmaceutical form: solution

Route of administration: subcutaneous

Metformin

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Interventions

Insulin glargine/Lixisenatide (HOE901/AVE0010)

Pharmaceutical form: solution

Route of administration: subcutaneous

Intervention Type: DRUG

Insulin glargine U100 (HOE901)

Pharmaceutical form: solution

Route of administration: subcutaneous

Intervention Type: DRUG

Metformin

Pharmaceutical form: tablet

Route of administration: oral

Intervention Type: DRUG

Other Intervention Names

LixiLan; Lantus

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.

• 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

• 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.
• 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.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

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, , Japan

Investigational Site Number 392151

Chiba, , 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

Chūōku, , Japan

Investigational Site Number 392017

Chūōku, , Japan

Investigational Site Number 392055

Chūōku, , Japan

Investigational Site Number 392008

Fujimi-Shi, , Japan

Investigational Site Number 392143

Fujisawa-Shi, , Japan

Investigational Site Number 392094

Fukuoka, , Japan

Investigational Site Number 392147

Fukuoka, , Japan

Investigational Site Number 392100

Gifu, , Japan

Investigational Site Number 392059

Hachioji-Shi, , Japan

Investigational Site Number 392048

Hamamatsu, , Japan

Investigational Site Number 392102

Hamamatsu, , 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, , 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, , Japan

Investigational Site Number 392044

Koga-Shi, , Japan

Investigational Site Number 392001

Koriyama-Shi, , Japan

Investigational Site Number 392028

Kumamoto, , Japan

Investigational Site Number 392092

Kumamoto, , Japan

Investigational Site Number 392108

Kumamoto, , Japan

Investigational Site Number 392116

Kumamoto, , Japan

Investigational Site Number 392099

Kushiro, , Japan

Investigational Site Number 392049

Kyoto, , Japan

Investigational Site Number 392107

Kyoto, , Japan

Investigational Site Number 392088

Maebashi, , Japan

Investigational Site Number 392158

Maebashi, , Japan

Investigational Site Number 392121

Matsuyama, , Japan

Investigational Site Number 392122

Minatoku, , Japan

Investigational Site Number 392076

Misato-Shi, , Japan

Investigational Site Number 392014

Mitaka-Shi, , Japan

Investigational Site Number 392042

Mito, , Japan

Investigational Site Number 392043

Mito, , Japan

Investigational Site Number 392078

Mito, , Japan

Investigational Site Number 392046

Miyazaki, , Japan

Investigational Site Number 392026

Nagoya, , Japan

Investigational Site Number 392101

Nagoya, , Japan

Investigational Site Number 392128

Nagoya, , Japan

Investigational Site Number 392131

Nagoya, , Japan

Investigational Site Number 392134

Nagoya, , Japan

Investigational Site Number 392137

Nagoya, , Japan

Investigational Site Number 392140

Nagoya, , Japan

Investigational Site Number 392154

Naka, , 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 392005

Okawa-Shi, , Japan

Investigational Site Number 392071

Okayama, , Japan

Investigational Site Number 392080

Okayama, , Japan

Investigational Site Number 392095

Onga-Gun, , Japan

Investigational Site Number 392105

Osaka, , Japan

Investigational Site Number 392117

Osaka, , Japan

Investigational Site Number 392144

Osaka, , Japan

Investigational Site Number 392125

Osaki-Shi, , Japan

Investigational Site Number 392157

Ota-Shi, , Japan

Investigational Site Number 392040

Oyama-Shi, , Japan

Investigational Site Number 392153

Ōita, , Japan

Investigational Site Number 392120

Ōta-ku, , 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, , Japan

Investigational Site Number 392106

Sapporo, , Japan

Investigational Site Number 392097

Sasebo-Shi, , Japan

Investigational Site Number 392015

Satsumasendai-Shi, , Japan

Investigational Site Number 392004

Sendai, , 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, , Japan

Investigational Site Number 392081

Shizuoka, , 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, , 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, , Japan

Investigational Site Number 392126

Yokohama, , Japan

Investigational Site Number 392035

Zentsuji-Shi, , Japan

Countries

Japan

References

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.

Reference Type: RESULT

PMID: 32072742 (View on PubMed)

Other Identifiers

U1111-1176-8378

Identifier Type: OTHER

Identifier Source: secondary_id

EFC14113

Identifier Type: -

Identifier Source: org_study_id