Effect of Lixisenatide on Postprandial Lipid Profile in Obese Type 2 Diabetic Patients

• ClinicalTrials.gov Identifier: NCT02274740
• Recruitment Status: Terminated
• First Posted: October 24, 2014
• Last Update Posted: January 30, 2017
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Tracking Information

• First Submitted Date: October 17, 2014
• First Posted Date: October 24, 2014
• Last Update Posted Date: January 30, 2017
• Study Start Date: April 2015
• Actual Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 22, 2014): Change in plasma triglycerides after 10 weeks of treatment area under-the-time concentration curve between 0 and 480 minutes (AUC0-480 min) [ Time Frame: After 10 weeks of treatment ]
• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT02274740 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: October 22, 2014)

• Change from baseline in plasma triglyceride [ Time Frame: 2 days after the basal test and after 10 weeks of treatment ]
• Change from baseline in plasma cholesterol [ Time Frame: 2 days after the basal test and after 10 weeks of treatment ]
• Change from baseline in APO B48 [ Time Frame: 2 days after the basal test and after 10 weeks of treatment ]
• Change from baseline in free fatty acid levels [ Time Frame: 2 days after the basal test and after 10 weeks of treatment ]
• Change from baseline in lipoprotein distribution [ Time Frame: 2 days after the basal test and after 10 weeks of treatment ]
• Change from baseline in LDL oxidation [ Time Frame: 2 days after the basal test and after 10 weeks of treatment ]
• Change from baseline in postprandial plasma glucose [ Time Frame: 2 days after the basal test and after 10 weeks of treatment ]
• Change from baseline in insulin [ Time Frame: 2 days after the basal test and after 10 weeks of treatment ]
• Change from baseline in C-peptide [ Time Frame: 2 days after the basal test and after 10 weeks of treatment ]
• Change from baseline in low grade inflammation (cytokines and stress oxidative markers) [ Time Frame: 2 days after the basal test and after 10 weeks of treatment ]
• Change in baseline coronary flow reserve to assess the effect of lixisenatide on microvascular dysfunction [ Time Frame: 2 days after the basal test and after 10 weeks of treatment ]

• 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: Effect of Lixisenatide on Postprandial Lipid Profile in Obese Type 2 Diabetic Patients
• Official Title: Effect of GLP-1 Receptors Agonist Lixisenatide on Postprandial Lipid Profile in Obese Type 2 Diabetic Patients

Brief Summary

Primary Objective:

To evaluate the ability of lixisenatide to modulate postprandial hyperlipidemia in particular, the effects on plasma changes in triglycerides.

Secondary Objectives:

The effect of lixisenatide on the following postprandial lipids: apolipoprotein (APO) B48; free fatty acid, lipoprotein distribution, cholesterol, and low-density lipoprotein (LDL) oxidation.

The effect of lixisenatide on chronic low-grade inflammation present in non-insulin dependent diabetes mellitus (NIDDM) and obesity.

The effect of lixisenatide on microvascular dysfunction. To evaluate the effect of lixisenatide on postprandial plasma glucose, insulin and C-peptide and glucagon.

• Detailed Description: Maximum study duration of approximately 2.5 months (study treatment) ± 2 days Day 0 (baseline) plus a 10-week open-label, active-controlled treatment period (Final/End-of-treatment Visit).
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Type II Diabetes Mellitus

Intervention

• Drug: LIXISENATIDE AVE0010
  Pharmaceutical form:solution Route of administration: subcutaneous
• Drug: metformin
  Pharmaceutical form:tablet Route of administration: oral

Study Arms

• Experimental: lixisenatide

  Lixisenatide injection should be performed in the morning, within 1 hour (ie, 0-60 minutes), prior to breakfast (or standardized meal).

  Lixisenatide is to be started with once daily injections of 10 μg per day for 2 weeks then to be continued by the maintenance dose (8 weeks) of 20 μg/d up to the end of the treatment period.

  Interventions:

  • Drug: LIXISENATIDE AVE0010
  • Drug: metformin
• No Intervention: metformin
  Greater than or equal than 1.5 g/day as background therapy for 10 weeks

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: August 26, 2015): 2
• Original Estimated Enrollment (submitted: October 22, 2014): 36
• Actual Study Completion Date: August 2015
• Actual Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria:

Male and female patients, 18-70 years of age.

Diagnosis of Type 2 diabetes treated with metformin and obesity (body mass index [BMI] >30 kg/m^2) and the following other abnormalities:

• Abdominal obesity (waist circumference >102 cm in men and >88 cm in women). According to National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATP) III (2001).
• Glycated hemoglobin A1c (HbA1c) ≥7 and ≤8.5% (after Sponsor approval providers might reasonably suggest more stringent A1c goals [such as 6.5%] for selected individual patients, if this can be achieved without significant hypoglycemia or other adverse effects of treatment. Appropriate patients might include those with short duration of diabetes, long life expectancy, and no significant cardiovascular disease).
• Hypertriglyceridemia (fasting triglyceride levels between 150 mg/dL and 600 mg/dL, cholesterol <300 mg/dL. In order to exclude patients who might be suffering from a primitive dyslipidemia).
• Low high-density lipoprotein (HDL) cholesterol (serum HDL-cholesterol <40 mg/dL in men and <50 mg/dL in women).

Written informed consent.

Exclusion criteria:

Smoking. Thyroid disease even if under appropriate hormonal replacement therapy or thyroid suppressant (Thyroid Stimulating Hormone [TSH] >5 mU/L with clinical symptoms of hypothyroidism).

Hepatic disease (Aspartate Aminotransferase [ASAT] or Alanine Aminotransferase [ALAT] >2 times the upper limit of normal).

Renal disease (serum creatinine >1.7 times the upper limit of normal). A history of coronary heart disease, cerebrovascular disease, or peripheral arterial disease in the 6 months before enrollment.

History of malignancies. Use of lipid lowering therapy. Systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg. Triglycerides >600 mg/dL. History of chronic pancreatitis or of idiopathic acute pancreatitis.

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 to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT02274740
• Other Study ID Numbers: LIXISL07016; U1111-1153-3774 ( Other Identifier: UTN )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Sanofi
• Study Sponsor: Sanofi
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: January 2017