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

NCT ID: NCT02749890

Last Updated: 2020-06-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 321 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-09
• Study Completion Date: 2018-05-31

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.

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.

Background therapy with OADs (except dipeptidyl-peptidase-4 inhibitor) should be continued during the treatment period.

Group Type: EXPERIMENTAL

Insulin glargine/Lixisenatide (HOE901/AVE0010)

Intervention Type: DRUG

Pharmaceutical form: solution

Route of administration: subcutaneous

Oral anti-diabetic drugs

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: Oral

lixisenatide

Lixisenatide (AVE0010) is injected subcutaneously (under the skin) once daily. It will be initiated with Dose 1 for 1 week and then continue with Dose 2 for 1 week followed by the maintenance dose of Dose 3 up to the end of treatment period.

Background therapy with OADs (except dipeptidyl-peptidase-4 inhibitor) should be continued during the treatment period.

Group Type: ACTIVE_COMPARATOR

Lixisenatide (AVE0010)

Intervention Type: DRUG

Pharmaceutical form: solution

Route of administration: subcutaneous

Oral anti-diabetic drugs

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

Lixisenatide (AVE0010)

Pharmaceutical form: solution

Route of administration: subcutaneous

Intervention Type: DRUG

Oral anti-diabetic drugs

Pharmaceutical form: tablet

Route of administration: Oral

Intervention Type: DRUG

Other Intervention Names

LixiLan

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.

• 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.

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.

• 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 392009

Arakawa-Ku, , Japan

Investigational Site Number 392025

Atsugi-Shi, , Japan

Investigational Site Number 392060

Bunkyō City, , Japan

Investigational Site Number 392024

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 392008

Fujimi-Shi, , Japan

Investigational Site Number 392054

Fukuoka, , Japan

Investigational Site Number 392094

Fukuoka, , Japan

Investigational Site Number 392059

Hachioji-Shi, , Japan

Investigational Site Number 392083

Hakodate-Shi, , Japan

Investigational Site Number 392048

Hamamatsu, , Japan

Investigational Site Number 392079

Hiki-Gun, , Japan

Investigational Site Number 392057

Iruma-Shi, , Japan

Investigational Site Number 392022

Ise-Shi, , Japan

Investigational Site Number 392023

Isehara-Shi, , Japan

Investigational Site Number 392020

Izumisano, , Japan

Investigational Site Number 392066

Kashiwa-Shi, , Japan

Investigational Site Number 392006

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 392077

Kawasaki-Shi, , Japan

Investigational Site Number 392082

Kawasaki-Shi, , Japan

Investigational Site Number 392031

Kitakyushu-Shi, , Japan

Investigational Site Number 392041

Kitakyusyu-Shi, , Japan

Investigational Site Number 392068

Kitakyusyu-Shi, , Japan

Investigational Site Number 392044

Koga-Shi, , Japan

Investigational Site Number 392001

Koriyama-Shi, , Japan

Investigational Site Number 392032

Kurume-Shi, , Japan

Investigational Site Number 392088

Maebashi, , Japan

Investigational Site Number 392014

Mitaka-Shi, , Japan

Investigational Site Number 392042

Mito, , Japan

Investigational Site Number 392078

Mito, , Japan

Investigational Site Number 392026

Nagoya, , Japan

Investigational Site Number 392080

Okayama, , 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 392047

Sapporo, , Japan

Investigational Site Number 392015

Satsumasendai-Shi, , Japan

Investigational Site Number 392004

Sendai, , Japan

Investigational Site Number 392034

Shimotsuke-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 392061

Tokorozawa-Shi, , Japan

Investigational Site Number 392029

Toyonaka-Shi, , Japan

Investigational Site Number 392093

Ube-Shi, , Japan

Investigational Site Number 392067

Yatsushiro-Shi, , Japan

Investigational Site Number 392035

Zentsuji-Shi, , Japan

Countries

Japan

References

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.

Reference Type: RESULT

PMID: 32295808 (View on PubMed)

Other Identifiers

U1111-1176-8357

Identifier Type: OTHER

Identifier Source: secondary_id

EFC14112

Identifier Type: -

Identifier Source: org_study_id