Efficacy and Safety of Liraglutide Versus Lixisenatide as add-on to Metformin in Subjects With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

— LIRA-LIXI™  

Official title:

Efficacy and Safety of Liraglutide Versus Lixisenatide as add-on to Metformin in Subjects With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01973231
• Other study ID #: NN2211-3867
• Secondary ID: 2012-004984-27U1
• Status: Completed
• Phase: Phase 4
• First received: October 23, 2013
• Last updated: December 21, 2015
• Start date: October 2013
• Est. completion date: November 2014

Study information

• Verified date: December 2015
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Health authority: Czech Republic: State Institute for Drug ControlFinland: Finnish Medicines AgencyFrance: Ministry of HealthGermany: Federal Institute for Drugs and Medical DevicesHungary: Ministry of Health, Social and Family AffairsItaly: Ministry of HealthLatvia: State Agency of MedicinesLithuania: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

This trial is conducted in Europe. The aim of the trial is to investigate the efficacy and safety of liraglutide versus lixisenatide as add-on to metformin in subjects with type 2 diabetes (T2DM).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 404
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial

• Subjects diagnosed with T2DM and on unchanged metformin treatment at the maximum tolerated dose (at least 1000 mg/day and up to 3000 mg/day) for at least 90 days prior to screening

• HbA1c 7.5 - 10.5% (53 mmol/mol - 91 mmol/mol) (both inclusive)

• Body Mass Index (BMI) equal to or above 20 kg/m^2

Exclusion Criteria:

• Female of child-bearing potential who is pregnant, breast-feeding or intend to become pregnant or is not using adequate contraceptive methods. (Adequate contraceptive measures as required by local law or practice)

• Treatment with glucose lowering agent(s) other than stated in the inclusion criteria in a period of 90 days prior to screening. Exception is short-term treatment (equal to or below 7 days in total) with insulin in connection with intercurrent illness

• History of chronic pancreatitis or idiopathic acute pancreatitis

• Screening calcitonin value equal to or above 50 ng/L

• Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2)

• Impaired liver function, defined as alanine aminotransferase (ALAT) equal to or above 2.5 times upper normal limit (UNL)

• Impaired renal function defined as estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m^2 per Modification of Diet in Renal Disease (MDRD) formula

• Any episode of unstable angina, acute coronary event, cerebral stroke/transient ischemic attack (TIA) or other significant cardiovascular event as judged by the investigator within 90 days prior to screening

• Heart failure, New York Heart Association (NYHA) class IV

• Uncontrolled hypertension (defined as systolic blood pressure equal to or above 180 mmHg and/or diastolic blood pressure equal to or above 100 mmHg)

• Diagnosis of malignant neoplasm in the previous 5 years (except basal cell skin cancer or squamous cell skin cancer)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• liraglutide
Starting dose of 0.6 mg/day, with weekly dose escalations of 0.6 mg/day until the maintenance dose of 1.8 mg/day is reached. Administered s.c. (subcutaneously, under the skin) once daily in addition to the subject's stable pre-trial metformin (equal to or above 1000 mg/day and up to 3000 mg/day).
• lixisenatide
Starting dose of 10 microg to be administered s.c. once daily, within the hour prior to the first meal of the day or the evening meal in addition to subject's stable pre-trial metformin (equal to or above 1000mg/day and up to 3000mg/day). Dose escalation to 20 microg s.c. once daily from day 15 after randomization.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

Czech Republic,  Finland,  France,  Germany,  Hungary,  Italy,  Latvia,  Lithuania,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Glycosylated Haemoglobin (HbA1c) From Baseline	Change from baseline in HbA1c after 26 weeks of treatment.	Week 0, week 26	No
Secondary	Change in Fasting Plasma Glucose (FPG) From Baseline	Change from baseline in FPG after 26 weeks of treatment.	Week 0, week 26	No
Secondary	Change in Body Weight From Baseline	Change from baseline in body weight after 26 weeks of treatment.	Week 0, week 26	No
Secondary	Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) (American Diabetes Association (ADA) Target) (Yes/no)	Subjects who achieved HbA1c below 7.0% (53 mmol/mol) after 26 weeks of treatment (yes/no).	After 26 weeks of treatment	No
Secondary	Subjects Who Achieve HbA1c Equal to or Below 6.5% (48 mmol/Mol) (American Association of Clinical Endocrinologists [AACE] Target) (Yes/no)	Subjects who achieved HbA1c below equal to or below 6.5% (48 mmol/mol) after 26 weeks of treatment (yes/no).	After 26 weeks of treatment	No
Secondary	Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) and no Weight Gain (Yes/no)	Subjects who achieved HbA1c below 7.0% (53 mmol/mol) and no weight gain after 26 weeks of treatment (yes/no).	After 26 weeks of treatment	No
Secondary	Number of Treatment Emergent Adverse Events (TEAEs)	A Treatment Emergent Adverse Event (TEAE) was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. Severity was assessed by investigator.	Weeks 0-26	No

External Links

•   Clinical Trials at Novo Nordisk