Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination Versus Insulin Glargine in Patients With Type 2 Diabetes (LixiLan-India)

A Randomized, 24-week, Controlled, Open Label, Parallel Arm, Multicenter Study Comparing the Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination to Insulin Glargine in Type 2 Diabetes Patients, Inadequately Controlled on Basal Insulin With or Without Metformin

Primary Objective:

To demonstrate the superiority of the insulin glargine/lixisenatide fixed ratio combination (FRC) to insulin glargine by demonstrating change in glycosylated hemoglobin (HbA1c).

Secondary Objectives:

• To assess the effects of the FRC in comparison with insulin glargine on:
• Percentage of patients reaching HbA1c targets (<7% );
• Glycemic control in relation to a meal as evaluated by 2-hour Post-prandial Plasma Glucose; (PPG);
• Body weight
• Fasting Plasma Glucose (FPG);
• Percentage of patients reaching HbA1c targets of <7% with no body weight gain and no hypoglycemia (as defined in the evaluation criteria);
• 7-point Self-Monitoring Plasma Glucose (SMPG) profile;
• Insulin glargine dose.
• To assess the safety and tolerability in each treatment group.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: INSULIN GLARGINE/LIXISENATIDE (HOE901/AVE0010); Drug: Metformin; Drug: Insulin Glulisine (HMR1964); Drug: INSULIN GLARGINE (HOE901)

Detailed Description

The maximum study duration per patient is 33 weeks.

• Study Type: Interventional
• Enrollment (Actual): 247
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Bangalore, India, 560092
    • Investigational Site Number 01
  • Belgaum, India, 590010
    • Investigational Site Number 012
  • Chennai, India, 600086
    • Investigational Site Number 013
  • Coimbatore, India, 641009
    • Investigational Site Number 017
  • Hyderabad, India, 500063
    • Investigational Site Number 06
  • Hyderabad, India, 500072
    • Investigational Site Number 07
  • Jaipur, India
    • Investigational Site Number 08
  • Kolkata, India, 700107
    • Investigational Site Number 04
  • Lucknow, India
    • Investigational Site Number 018
  • Madurai, India, 625020
    • Investigational Site Number 014
  • Nasik, India, 422002
    • Investigational Site Number 05
  • New Delhi, India, 110029
    • Investigational Site Number 010
  • Pune, India, 411040
    • Investigational Site Number 016

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 62 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria :

• Patients with type 2 diabetes mellitus (T2DM) diagnosed for at least 1 year before the screening visit,
• At screening:
• Age should be ≥ 18 years of age to < 65 years;
• Glycosylated hemoglobin (HbA1c) at screening visit ≥ 7.5% or ≤ 10%;
• Body mass index (BMI) ≥ 19 kg/m2 and ≤ 40 kg/m2.
• Patients who have been treated with a basal insulin for at least 6 months before the screening visit, and who have been on a stable basal insulin regimen (ie, type of insulin and time/frequency of the injection), for at least 3 months before the screening visit. The stable total daily dose should be within the range of 15-40 U, both inclusive, on the day of screening, but individual fluctuations of ± 20% within 2 months prior to screening are acceptable.

Exclusion criteria:

• Use of oral or injectable glucose-lowering agents other than those stated in the inclusion criteria in the 3 months before screening.
• Previous use of insulin regimen other than basal insulin eg, prandial or pre-mixed insulin (Note: Short term treatment due to intercurrent illness including gestational diabetes is allowed at the discretion of the investigator).
• For patients taking metformin, any contraindication to metformin use, according to local labeling.
• For patient not treated with metformin at screening: severe renal function impairment with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 or end-stage renal disease.
• Personal or immediate family history of medullary thyroid cancer (MTC) or genetic condition that predisposes to MTC (eg, multiple endocrine neoplasia syndromes).
• Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including (but not limited to): gastroparesis, unstable (ie, worsening) or not controlled (ie, prolonged nausea and vomiting) gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening visit; or history of surgery affecting gastric emptying.
• History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy has been performed), pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, pancreatectomy.
• Average insulin glargine daily dose <20 U or >50 U calculated for the last 3 days before Visit 6.
• Amylase and/or lipase >3 upper limit normal (ULN) at Visit 5 (Week -1).

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tested Drug; Insulin glargine/lixisenatide fixed ratio combination (FRC)	Drug: INSULIN GLARGINE/LIXISENATIDE (HOE901/AVE0010); Pharmaceutical form: Injection Route of administration: Subcutaneous; Other Names: Soliqua, Insulin Glargine/Lixisenatide Fixed Ratio Combination; Drug: Metformin; Pharmaceutical form: Tablet Route of administration: Oral; Drug: Insulin Glulisine (HMR1964); Pharmaceutical form: Injection Route of administration: Subcutaneous; Other Names: Apidra
Active Comparator: Control Drug; Insulin glargine (Lantus®)	Drug: Metformin; Pharmaceutical form: Tablet Route of administration: Oral; Drug: Insulin Glulisine (HMR1964); Pharmaceutical form: Injection Route of administration: Subcutaneous; Other Names: Apidra; Drug: INSULIN GLARGINE (HOE901); Pharmaceutical form: Injection Route of administration: Subcutaneous; Other Names: Lantus®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c	Mean change in glycosylated hemoglobin (HbA1c) from baseline to Week 24	From baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients with HbA1c <7%	Number of patients reaching HbA1c <7 % at the end of Week 24	At Week 24
Change in 2-hour Post prandial glucose (PPG)	Change in 2-hour PPG from baseline to Week 24	From baseline to Week 24
Change in body weight	Change in body weight from baseline to Week 24	From baseline to Week 24
Patients with HbA1c <7% with no body weight gain and no hypoglycemia	Number of patients reaching HbA1c <7% with no body weight gain and no hypoglycemia at the end of Week 24	At Week 24
Change in Fasting Plasma Glucose	Mean change in FPG from baseline to Week 24	From baseline to Week 24
Adverse events (AE)	Number of AEs	Up to 33 weeks
Patients with HbA1c <7% with no body weight gain	Number of patients reaching HbA1c <7% with no body weight gain at the end of Week 24	At Week 24
Change in SMPG profiles	Change in 7-point self-monitoring plasma glucose (SMPG) profiles from baseline to Week 24	From baseline to Week 24

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2018
• Primary Completion (Actual): November 25, 2019
• Study Completion (Actual): November 25, 2019

Study Registration Dates

• First Submitted: May 7, 2018
• First Submitted That Met QC Criteria: May 7, 2018
• First Posted (Actual): May 18, 2018

Study Record Updates

• Last Update Posted (Actual): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 21, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Metformin; Insulin Glargine; Insulin glulisine; Lixisenatide
• Other Study ID Numbers: INSLIL08556; U1111-1200-1162 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No