Clinical trial NCT01620489: Efficacy and Safety of Liraglutide Versus Placebo as add-on to Existing Diabetes Medication in Subjects With Type 2 Diabetes and Moderate Renal Impairment
Official title: Efficacy and Safety of Liraglutide Versus Placebo as add-on to Existing Diabetes Medication in Subjects With Type 2 Diabetes and Moderate Renal Impairment. A 26-week Double-blind Placebo-controlled, Randomised, Multicentre, Multi-national, Parallel-group Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2012-06-15
Enrollment: 279
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is conducted in Europe and the United States of America (USA). The aim of this trial is to investigate the efficacy and safety of liraglutide in subjects with type 2 diabetes and moderate renal impairment.

The trial medication will be add-on to the subject's stable pre-trial OAD and/or insulin regimen.


Eligibility criteria: Inclusion Criteria:

* Subjects diagnosed with type 2 diabetes with stable diabetes treatment (unchanged medication and unchanged dose) for 90 days prior to the screening visit including: Monotherapy or any duo-combinations of metformin and/or SUs and/or pioglitazone. Metformin should be used with caution in subjects with moderate renal failure and must be used in accordance with local metformin labelling or guidelines. Or Monotherapy or any combinations of metformin and/or pioglitazone and/or basal or premix insulin. Insulin adjustments (total daily dose) below or equal to 10% within 90 days prior to the screening visit as confirmed by the investigator are acceptable. Metformin should be used with caution in subjects with moderate renal failure and must be used in accordance with local metformin labelling or guidelines. Combination of pioglitazone and insulin should be used with caution and according to local labelling or guidelines
* HbA1c 7-10% (both inclusive)
* Moderate renal impairment diagnosed more than 90 days prior to the screening visit and confirmed by an eGFR (glomerular filtration rate) of 30-59 mL/min/1.73 m2 per MDRD (modification of diet in renal disease) formula at the screening visit
* Body Mass Index (BMI) 20-45 kg/m\^2 (both inclusive)

Exclusion Criteria:

* Recurrent severe hypoglycaemia or hypoglycaemic unawareness as judged by the investigator
* Treatment with antidiabetic medication(s) other than stated in the inclusion criteria in a period of 90 days prior to screening. Previous short-term (below or equal to 7 days in total) treatment with rapid-or short-acting insulin in connection with intercurrent illness is allowed at the discretion of the investigator
* Impaired liver function, defined as ALAT (alanine aminotransferase) above or equal to 2.5 times upper normal limit
* History of chronic pancreatitis or idiopathic acute pancreatitis
* Within the past 180 days any of the following: Episode of unstable angina, acute coronary event, cerebral stroke/transient ischemic attack (TIA) or other significant cardiovascular event (including e.g. arrhythmias or conduction delays on ECG (electrocardiogram))
* Heart failure defined as New York Heart Association (NYHA) class IV
* A systolic blood pressure above or equal to 180 mmHg or a diastolic blood pressure above or equal to 100 mmHg
* Rapidly progressing renal disease (e.g., acute glomerulonephritis) at the discretion of the investigator
* Use of immunosuppressive treatment within 90 days prior to screening
* Diagnosis or treatment for cancer in the previous 5 years (except basal cell skin cancer or squamous cell skin cancer)
* Proliferative retinopathy or maculopathy requiring acute treatment as judged by the investigator

Primary outcomes:
measure: Estimated Mean From the Statistical Model and Standard Deviation From Observed Data For Change From Baseline to Week 26 in HbA1c (%) (Glycosylated Haemoglobin)
timeFrame: Week 0, Week 26
Secondary outcomes:
measure: Estimated Proportion of Responders Achieving HbA1c <7.0% and no Weight Gain After 26 Weeks of Treatment
timeFrame: At week 26
measure: Estimated Proportion of Responders Achieving HbA1c <7.0% and no Minor or Severe Hypoglycaemic Episodes After 26 Weeks of Treatment
timeFrame: At week 26
measure: Estimated Mean From the Statistical Model and Standard Deviation From Observed Data For Change From Baseline to Week 26 in Self-measured Plasma Glucose (SMPG) 7-point Profiles
timeFrame: Week 0, week 26
measure: Estimated Mean From the Statistical Model and Standard Deviation From Observed Data For Change From Baseline to Week 26 in Body Mass Index (BMI)
timeFrame: Week 0, week 26
measure: Estimated Mean Ratio to Baseline and Observed Coefficient of Variation in Renal Function-estimated Glomerular Filtration Rate (eGFR) (to Check How Well the Kidneys Are Functioning Using Modification of Diet in Renal Disease (MDRD) Formula)
timeFrame: Week 0, week 26
Other outcomes:
Locations:
city: Concord
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: La Jolla
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Los Angeles
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Monterey
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: San Diego
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: San Ramon
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Torrance
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Tustin
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Ventura
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Golden
country: United States
facility: Novo Nordisk Investigational Site
state: Colorado
city: Boynton Beach
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Miami
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Pembroke Pines
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Plantation
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Saint Petersburg
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Roswell
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Avon
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Franklin
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Greenfield
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Muncie
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Slidell
country: United States
facility: Novo Nordisk Investigational Site
state: Louisiana
city: Rockville
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Springfield
country: United States
facility: Novo Nordisk Investigational Site
state: Massachusetts
city: Buckley
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Southfield
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Great Falls
country: United States
facility: Novo Nordisk Investigational Site
state: Montana
city: Nashua
country: United States
facility: Novo Nordisk Investigational Site
state: New Hampshire
city: Rosedale
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Staten Island
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Greenville
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Mooresville
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Franklin
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Mason
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Wadsworth
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: Novo Nordisk Investigational Site
state: Oklahoma
city: McMurray
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Norristown
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: East Providence
country: United States
facility: Novo Nordisk Investigational Site
state: Rhode Island
city: Chattanooga
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Chattanooga
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Kingsport
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Amarillo
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Lubbock
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Sugar Land
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Newport News
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Richmond
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Richmond
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Richmond
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Winchester
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Milwaukee
country: United States
facility: Novo Nordisk Investigational Site
state: Wisconsin
city: Brest
country: France
facility: Novo Nordisk Investigational Site
city: LA ROCHE-sur-YON cedex 9
country: France
facility: Novo Nordisk Investigational Site
city: LA ROCHELLE cedex
country: France
facility: Novo Nordisk Investigational Site
city: Pointe À Pitre
country: France
facility: Novo Nordisk Investigational Site
city: Strasbourg
country: France
facility: Novo Nordisk Investigational Site
city: Bialystok
country: Poland
facility: Novo Nordisk Investigational Site
city: Bialystok
country: Poland
facility: Novo Nordisk Investigational Site
city: Gdansk
country: Poland
facility: Novo Nordisk Investigational Site
city: Katowice
country: Poland
facility: Novo Nordisk Investigational Site
city: Krakow
country: Poland
facility: Novo Nordisk Investigational Site
city: Poznan
country: Poland
facility: Novo Nordisk Investigational Site
city: Poznan
country: Poland
facility: Novo Nordisk Investigational Site
city: Zabrze
country: Poland
facility: Novo Nordisk Investigational Site
city: Barnaul
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Kazan
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Kursk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Moscow
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Moscow
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Moscow
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Nizhniy Novgorod
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Penza
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Samara
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saratov
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saratov
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saratov
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Smolensk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Volgograd
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Kharkiv
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Kiev
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Kyiv
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Vinnytsia
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Zaporizhia
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Bristol
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Dundee
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Edinburgh
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Hull
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Leicester
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Letchworth
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: London
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: London
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Swansea
country: United Kingdom
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR, 1452)
role: STUDY_DIRECTOR
References:
citation: Davies MJ, Bain SC, Atkin SL, Rossing P, Scott D, Shamkhalova MS, Bosch-Traberg H, Syren A, Umpierrez GE. Efficacy and Safety of Liraglutide Versus Placebo as Add-on to Glucose-Lowering Therapy in Patients With Type 2 Diabetes and Moderate Renal Impairment (LIRA-RENAL): A Randomized Clinical Trial. Diabetes Care. 2016 Feb;39(2):222-30. doi: 10.2337/dc14-2883. Epub 2015 Dec 17.
citation: Zobel EH, von Scholten BJ, Goldman B, Persson F, Hansen TW, Rossing P. Pleiotropic effects of liraglutide in patients with type 2 diabetes and moderate renal impairment: Individual effects of treatment. Diabetes Obes Metab. 2019 May;21(5):1261-1265. doi: 10.1111/dom.13638. Epub 2019 Feb 22.
citation: Kim JD, Park CY, Cha BY, Ahn KJ, Kim IJ, Park KS, Lee HW, Min KW, Won JC, Chung MY, Kim JT, Kang JG, Park SW. Comparison of Adherence to Glimepiride/Metformin Sustained Release Once-daily Versus Glimepiride/Metformin Immediate Release BID Fixed-combination Therapy Using the Medication Event Monitoring System in Patients With Type 2 Diabetes. Clin Ther. 2018 May;40(5):752-761.e2. doi: 10.1016/j.clinthera.2018.04.002. Epub 2018 May 3.