Safety Assessment of Lyxumia (Lixisenatide) and Sulfonylurea as Add-on Treatment to Basal Insulin in Uncontrolled Patients With Type 2 Diabetes Mellitus Who Elect to Fast During Ramadan (LixiRam)

• ClinicalTrials.gov Identifier: NCT02941367
• Recruitment Status: Completed
• First Posted: October 21, 2016
• Last Update Posted: September 21, 2017
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

Brief Summary:

Primary Objective:

To compare the safety, in terms of percentage of patients with symptomatic documented hypoglycemia during Ramadan fast, of lixisenatide versus sulfonylurea (SU).

Secondary Objectives:

• To assess effect of lixisenatide versus SU on:
• Changes in glycemic control;
• Changes in body weight.
• To assess overall safety of lixisenatide and SU.

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus, Type 2	Drug: Lixisenatide (AVE0010); Drug: Sulfonylurea; Drug: metformin; Drug: basal insulin	Phase 4

Detailed Description:

The total study duration per patient will have a minimum 12 weeks and maximum 22 weeks (up to 2 weeks screening period + 8-12 weeks pre-Ramadan period + 29-30 days Ramadan + 0 4 weeks post-Ramadan period). This is a phase 3b study in Kingdom of Saudi Arabia and Bangladesh (instead of phase 4 for other countries).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 184 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: International, Randomized, Open Label Study to Compare the Safety and Efficacy of Lixisenatide vs. Sulfonylurea on Top of Basal Insulin Treatment in Type 2 Diabetes Mellitus Subjects Who Elect to Fast During Ramadan
• Actual Study Start Date: February 23, 2017
• Actual Primary Completion Date: August 4, 2017
• Actual Study Completion Date: August 4, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Lyxumia; Patients will receive Lyxumia once daily as investigational medicinal product (IMP) on top of patient's previous basal insulin with/without metformin. Non-IMPs will be administrated as per Investigator's indications according to local labeling, guidelines, and clinical judgment.	Drug: Lixisenatide (AVE0010); Pharmaceutical form: solution for injection Route of administration: subcutaneous; Other Name: Lyxumia; Drug: metformin; Pharmaceutical form: tablet Route of administration: oral; Drug: basal insulin; Pharmaceutical form: solution for injection Route of administration: subcutaneous
Active Comparator: Sulfonylurea; Patients will continue the treatment with previous Sulfonylurea as IMP on top of patient's previous basal insulin with/without metformin. The IMP and non-IMPs will be administrated as per Investigator's indications according to local labeling, guidelines, and clinical judgment.	Drug: Sulfonylurea; Pharmaceutical form: tablet Route of administration: oral; Drug: metformin; Pharmaceutical form: tablet Route of administration: oral; Drug: basal insulin; Pharmaceutical form: solution for injection Route of administration: subcutaneous

Outcome Measures

Primary Outcome Measures :

1. Percentage of patients with at least 1 documented symptomatic hypoglycemia event (plasma glucose ≤70 mg/dL; 3.9 mmol/L) [ Time Frame: Approximately 30 days (from start to end of Ramadan holy month) ]

Secondary Outcome Measures :

1. Mean change in HbA1c [ Time Frame: Baseline, 0-4 weeks pre- and 0-4 weeks post-Ramadan ]
2. Mean change in body weight [ Time Frame: Baseline, 0-4 weeks pre- and 0-4 weeks post-Ramadan ]
3. Percentage of patients with 2-hour post prandial glucose (2hPPG) <180 mg/dL (10 mmol/L) [ Time Frame: Last 14 days of Ramadan month ]
4. Percentage of patients with HbA1C <7% [ Time Frame: At 0-4 weeks pre- and 0-4 weeks post-Ramadan ]
5. Percentage of patients with fasting plasma glucose (FPG) <130 mg/dL (7.22 mmol/L) [ Time Frame: At pre-Ramadan visit ]
6. Percentage of patients with HbA1c <7%, no weight gain and no documented symptomatic hypoglycemia (plasma glucose ≤70 mg/dL; 3.9 mmol/L) [ Time Frame: At 0-4 weeks pre- and 0-4 weeks post-Ramadan ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria :

• Patients with type 2 diabetes mellitus, diagnosed for at least 1 year at the time of the screening visit, insufficiently controlled with basal insulin + SU (≤50% max allowed dose) ±1 oral antidiabetic (OAD) drug.
• Patients who express the intention to fast during Ramadan.
• Signed informed consent.

Exclusion criteria:

• At the time of screening age < legal age of majority.
• Glycated hemoglobin (HbA1c) at screening visit: <7.5% or >10%.
• Body mass index (BMI) <20kg/m^2.
• Treatment with basal insulin for less than 6 months prior to screening.
• Prior antidiabetic medication (basal insulin and OADs) not at stable dose (eg, same medication, frequency and <20% dose change) in the last 8 weeks prior to screening.
• Previous treatment with short or rapid acting insulin other than for short term use (≤10 days) in relation to hospitalization or an acute illness in the last 6 months prior to screening.
• Any discontinuation from a glucagon like peptide-1 receptor agonist (GLP-1 RA) due to safety/tolerability issue or lack of efficacy.
• Patient not willing to perform self-monitored plasma glucose (SMPG) as required by protocol and to follow the instructions provided.
• Type 1, gestational or secondary diabetes.
• History of diabetic ketoacidosis.
• History of hypoglycemia unawareness.
• Any medical contraindication for sustained and safe fasting.
• Pregnant or breast-feeding women.
• Women of childbearing potential (WOCB) not protected by highly effective contraceptive method(s) of birth control and/or who are unwilling or unable to be tested for pregnancy.
• Known hypersensitivity/intolerance to lixisenatide (Lyxumia) or any of its excipients.
• All contraindications of the comparator and protocol mandated background therapies or warning/precaution of use (when appropriate) as displayed in the respective National Product Labeling.

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

Contacts and Locations

Locations

India

Investigational Site Number 356005

Ahmedabad, India, 380007

Investigational Site Number 356002

Bangalore, India, 560043

Investigational Site Number 356015

Bangalore, India, 560055

Investigational Site Number 356008

Bangalore, India, 560060

Investigational Site Number 356009

Hyderabad, India, 500001

Investigational Site Number 356018

Hyderabad, India, 500004

Investigational Site Number 356010

Hyderabad, India, 500072

Investigational Site Number 356003

Hyderabad, India, 500095

Investigational Site Number 356007

Jaipur, India

Investigational Site Number 356019

Madurai, India, 625020

Investigational Site Number 356014

Mumbai, India, 400007

Investigational Site Number 356022

Nagpur, India, 440010

Israel

Investigational Site Number 376001

Haifa, Israel, 31096

Investigational Site Number 376002

Safed, Israel, 13100

Kuwait

Investigational Site Number 414001

Kuwait, Kuwait

Turkey

Investigational Site Number 792002

Zonguldak, Turkey

Sponsors and Collaborators

Sanofi

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT02941367 History of Changes
• Other Study ID Numbers: LPS14410; U1111-1172-3026 ( Other Identifier: UTN )
• First Posted: October 21, 2016
• Last Update Posted: September 21, 2017
• Last Verified: September 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Individual participant data (IPD) and supporting clinical documents are available for request at clinicalstudydatarequest.com. While making information available we continue to protect the privacy of the participants in our clinical trials and to remove commercially confidential information (CCI). Details on Data Sharing criteria and process for requesting access can be found at this web address: clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lixisenatide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Insulin; Insulin, Globin Zinc; Metformin; Hypoglycemic Agents; Physiological Effects of Drugs