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

Tracking Information

• First Submitted Date: October 12, 2016
• First Posted Date: October 21, 2016
• Last Update Posted Date: September 21, 2017
• Actual Study Start Date: February 23, 2017
• Actual Primary Completion Date: August 4, 2017 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 20, 2016): 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) ]
• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT02941367 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: October 20, 2016)

• Mean change in HbA1c [ Time Frame: Baseline, 0-4 weeks pre- and 0-4 weeks post-Ramadan ]
• Mean change in body weight [ Time Frame: Baseline, 0-4 weeks pre- and 0-4 weeks post-Ramadan ]
• Percentage of patients with 2-hour post prandial glucose (2hPPG) <180 mg/dL (10 mmol/L) [ Time Frame: Last 14 days of Ramadan month ]
• Percentage of patients with HbA1C <7% [ Time Frame: At 0-4 weeks pre- and 0-4 weeks post-Ramadan ]
• Percentage of patients with fasting plasma glucose (FPG) <130 mg/dL (7.22 mmol/L) [ Time Frame: At pre-Ramadan visit ]
• 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 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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

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.

• 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 Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Diabetes Mellitus, Type 2

Intervention

• Drug: Lixisenatide (AVE0010)

  Pharmaceutical form: solution for injection

  Route of administration: subcutaneous

  Other Name: Lyxumia
• 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

Study Arms

• 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.
  Interventions:

  • Drug: Lixisenatide (AVE0010)
  • Drug: metformin
  • Drug: basal insulin
• 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.
  Interventions:

  • Drug: Sulfonylurea
  • Drug: metformin
  • Drug: basal insulin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 20, 2017): 184
• Original Estimated Enrollment (submitted: October 20, 2016): 236
• Actual Study Completion Date: August 4, 2017
• Actual Primary Completion Date: August 4, 2017 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: India, Israel, Kuwait, Turkey

Administrative Information

• NCT Number: NCT02941367
• Other Study ID Numbers: LPS14410; U1111-1172-3026 ( Other Identifier: UTN )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

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

• Responsible Party: Sanofi
• Study Sponsor: Sanofi
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: September 2017