Efficacy and Safety of Insulin Glargine/ Lixisenatide Fixed Ratio Combination Compared to Insulin Glargine Alone and Lixisenatide Alone on Top of Metformin in Patients With T2DM (LixiLan-O)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Sanofi
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT02058147
First received: February 6, 2014
Last updated: August 13, 2014
Last verified: August 2014
  Purpose

Primary Objective:

To compare the insulin glargine/lixisenatide fixed ratio combination to lixisenatide alone and to insulin glargine alone (on top of metformin treatment) in HbA1c change from baseline to week 30.

Secondary Objective:

To compare the overall efficacy and safety of insulin glargine/lixisenatide fixed ratio combination to insulin glargine alone and to lixisenatide alone (on top of metformin treatment) over a 30 week treatment period in patients with type 2 diabetes


Condition Intervention Phase
Type 2 Diabetes
Drug: Insulin glargine/lixisenatide HOE901/AVE0010
Drug: Insulin glargine HOE901
Drug: Lixisenatide AVE0010
Drug: Metformin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, 30 Week, Active-controlled, Open-label, 3-treatment Arm, Parallel-group Multicenter Study Comparing the Efficacy and Safety of Insulin Glargine/ Lixisenatide Fixed Ratio Combination to Insulin Glargine Alone and to Lixisenatide Alone on Top of Metformin in Patients With Type 2 Diabetes Mellitus T2DM

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Change in HbA1c from baseline [ Time Frame: week 30 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of patients reaching HbA1c targets [ Time Frame: week 30 ] [ Designated as safety issue: No ]
  • Change in 2-hour Post Prandial Glucose and in blood glucose excursion during standardized meal test from baseline [ Time Frame: week 30 ] [ Designated as safety issue: No ]
  • Change in body weight from baseline [ Time Frame: week 30 ] [ Designated as safety issue: No ]
  • Change in 7-point Self Measured Plasma Glucose profiles from baseline [ Time Frame: week 30 ] [ Designated as safety issue: No ]
  • Daily dose of insulin glargine [ Time Frame: week 30 ] [ Designated as safety issue: No ]
  • Change in Fasting Plasma Glucose from baseline [ Time Frame: week 30 ] [ Designated as safety issue: No ]
  • Documented (plasma glucose less than or equal to 70 mg/dl) symptomatic hypoglycemia [ Time Frame: week 30 ] [ Designated as safety issue: Yes ]
  • Severe symptomatic hypoglycemia [ Time Frame: week 30 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 1125
Study Start Date: February 2014
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Insulin glargine/lixisenatide fixed ratio combination
Insulin glargine/lixisenatide fixed ratio combination is injected subcutaneously (under the skin) once daily. Dose individually adjusted. Metformin treatment should be continued.
Drug: Insulin glargine/lixisenatide HOE901/AVE0010
Pharmaceutical form:solution for injection (disposable self injector) Route of administration: subcutaneous injection
Drug: Metformin
Pharmaceutical form: tablet Route of administration: Oral
Active Comparator: Insulin glargine
Insulin glargine is injected subcutaneously (under the skin) once daily. Dose individually adjusted. Metformin treatment should be continued.
Drug: Insulin glargine HOE901
Pharmaceutical form:solution for injection (disposable self injector) Route of administration: subcutaneous injection
Drug: Metformin
Pharmaceutical form: tablet Route of administration: Oral
Active Comparator: Lixisenatide
Lixisenatide is injected subcutaneously (under the skin) once daily. Starting dose will be 10µg, then increased to the 20µg maintenance dose after 2 weeks. Metformin treatment should be continued.
Drug: Lixisenatide AVE0010
Pharmaceutical form:solution for injection (disposable self injector) Route of administration: subcutaneous injection
Drug: Metformin
Pharmaceutical form: tablet Route of administration: Oral

Detailed Description:

Approximately 37 weeks including up to 6 weeks of screening, 30-week treatment period, and a 3 days follow-up period

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

  • Patients with type 2 diabetes mellitus diagnosed for at least 1 year before the screening visit, treated for at least 3 months prior to visit 1 with metformin alone or metformin and a second oral anti-diabetic treatment that can be a sulfonylurea, or a glinide, or a sodium glucose co-transporter 2 inhibitor, and who are not adequately controlled with this treatment;
  • Signed written informed consent

Exclusion criteria:

  • HbA1c at screening visit:

    • less than 7.5% or more than 10% for patients previously treated with metformin alone,
    • less than 7.0% or more than 9 % for patients previously treated with metformin and a second oral anti-diabetic treatment;
  • Pregnancy or lactation, women of childbearing potential with no effective contraceptive method;
  • Use of oral glucose-lowering agents other than those stated in the inclusion criteria or any injectable glucose-lowering agents during the 3 months before screening.
  • Previous Treatment with insulin (except for short-term treatment due to intercurrent illness including gestational diabetes, at the discretion of the trial physician)
  • History of discontinuation of a previous treatment with a GLP-1 receptor agonist (GLP-1 RA) due to safety/tolerability issue or lack of efficacy;
  • Patient who has previously participated in any clinical trial with lixisenatide or the insulin glargine/lixisenatide fixed ratio combination or has previously received lixisenatide.
  • Any contraindication to metformin use, according to local labeling
  • Use of weight loss drugs within 3 months prior to screening visit.
  • Within the last 6 months prior to screening visit: history of stroke, myocardial infarction, unstable angina, or heart failure requiring hospitalization. Planned coronary, carotid or peripheral artery revascularisation procedures to be performed during the study period.
  • History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy was already performed), chronic pancreatitis, pancreatitis during a previous treatment with incretin therapies, pancreatectomy, stomach/gastric surgery.
  • Personal or immediate family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (eg, multiple endocrine neoplasia syndromes).
  • Uncontrolled or inadequately controlled hypertension (systolic blood pressure above 180 mmHg or diastolic blood pressure above 95 mmHg) at screening visit
  • At screening visit, Body Mass Index (BMI) less than or equal to 20 or above 40 kg/m²
  • At screening visit amylase and/or lipase more than 3 times the upper limit of the normal (ULN) laboratory range,
  • At screening visit ALT or AST more than 3 ULN
  • At screening visit calcitonin above or equal to 20 pg/mL (5.9 pmol/L)

Exclusion Criteria for randomization at the end of the screening period:

  • HbA1c less than 7% or above 10%;
  • Fasting Plasma glucose above 250mg/dL (13.9 mmol/L);
  • Metformin maximal tolerated dose less than 1500 mg/day;
  • Amylase and/or lipase more than 3 ULN;

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02058147

Contacts
Contact: For site information, send an email with site number to Contact-Us@sanofi.com

  Show 292 Study Locations
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02058147     History of Changes
Other Study ID Numbers: EFC12404, 2013-003131-30, U1111-1148-4334
Study First Received: February 6, 2014
Last Updated: August 13, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Glargine
Insulin
Metformin
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 18, 2014