Efficacy and Safety of Liraglutide Versus Placebo as add-on to Existing Diabetes Medication in Subjects With Type 2 Diabetes and Moderate Renal Impairment

Diabetes Mellitus, Type 2 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01620489
• Other study ID #: NN2211-3916
• Secondary ID: 2011-002968-24U1
• Status: Completed
• Phase: Phase 3
• Start date: June 14, 2012
• Est. completion date: August 20, 2013

Study information

• Verified date: March 2019
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 279
• Est. completion date: August 20, 2013
• Est. primary completion date: August 20, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Renal Insufficiency

Intervention

Drug:
• liraglutide
1.8 mg administered once daily subcutaneously (s.c., under the skin) as add-on to the subject's stable pre-trial oral antidiabetic drug (OAD) and/or insulin regimen.
• placebo
Administered once daily subcutaneously (s.c., under the skin) as add-on to the subject's stable pre-trial oral antidiabetic drug (OAD) and/or insulin regimen.

Locations

Country	Name	City	State
France	Novo Nordisk Investigational Site	Brest
France	Novo Nordisk Investigational Site	LA ROCHE-sur-YON cedex 9
France	Novo Nordisk Investigational Site	LA ROCHELLE cedex
France	Novo Nordisk Investigational Site	Pointe À Pitre
France	Novo Nordisk Investigational Site	Strasbourg
Poland	Novo Nordisk Investigational Site	Bialystok
Poland	Novo Nordisk Investigational Site	Bialystok
Poland	Novo Nordisk Investigational Site	Gdansk
Poland	Novo Nordisk Investigational Site	Katowice
Poland	Novo Nordisk Investigational Site	Krakow
Poland	Novo Nordisk Investigational Site	Poznan
Poland	Novo Nordisk Investigational Site	Poznan
Poland	Novo Nordisk Investigational Site	Zabrze
Russian Federation	Novo Nordisk Investigational Site	Barnaul
Russian Federation	Novo Nordisk Investigational Site	Kazan
Russian Federation	Novo Nordisk Investigational Site	Kursk
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Nizhniy Novgorod
Russian Federation	Novo Nordisk Investigational Site	Penza
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
Russian Federation	Novo Nordisk Investigational Site	Samara
Russian Federation	Novo Nordisk Investigational Site	Saratov
Russian Federation	Novo Nordisk Investigational Site	Saratov
Russian Federation	Novo Nordisk Investigational Site	Saratov
Russian Federation	Novo Nordisk Investigational Site	Smolensk
Russian Federation	Novo Nordisk Investigational Site	Volgograd
Ukraine	Novo Nordisk Investigational Site	Kharkiv
Ukraine	Novo Nordisk Investigational Site	Kiev
Ukraine	Novo Nordisk Investigational Site	Kyiv
Ukraine	Novo Nordisk Investigational Site	Vinnytsia
Ukraine	Novo Nordisk Investigational Site	Zaporizhia
United Kingdom	Novo Nordisk Investigational Site	Bristol
United Kingdom	Novo Nordisk Investigational Site	Dundee
United Kingdom	Novo Nordisk Investigational Site	Edinburgh
United Kingdom	Novo Nordisk Investigational Site	Hull
United Kingdom	Novo Nordisk Investigational Site	Leicester
United Kingdom	Novo Nordisk Investigational Site	Letchworth
United Kingdom	Novo Nordisk Investigational Site	London
United Kingdom	Novo Nordisk Investigational Site	London
United Kingdom	Novo Nordisk Investigational Site	Swansea
United States	Novo Nordisk Investigational Site	Amarillo	Texas
United States	Novo Nordisk Investigational Site	Atlanta	Georgia
United States	Novo Nordisk Investigational Site	Avon	Indiana
United States	Novo Nordisk Investigational Site	Boynton Beach	Florida
United States	Novo Nordisk Investigational Site	Buckley	Michigan
United States	Novo Nordisk Investigational Site	Chattanooga	Tennessee
United States	Novo Nordisk Investigational Site	Chattanooga	Tennessee
United States	Novo Nordisk Investigational Site	Concord	California
United States	Novo Nordisk Investigational Site	East Providence	Rhode Island
United States	Novo Nordisk Investigational Site	Franklin	Indiana
United States	Novo Nordisk Investigational Site	Franklin	Ohio
United States	Novo Nordisk Investigational Site	Golden	Colorado
United States	Novo Nordisk Investigational Site	Great Falls	Montana
United States	Novo Nordisk Investigational Site	Greenfield	Indiana
United States	Novo Nordisk Investigational Site	Greenville	North Carolina
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Kingsport	Tennessee
United States	Novo Nordisk Investigational Site	La Jolla	California
United States	Novo Nordisk Investigational Site	Los Angeles	California
United States	Novo Nordisk Investigational Site	Lubbock	Texas
United States	Novo Nordisk Investigational Site	Mason	Ohio
United States	Novo Nordisk Investigational Site	McMurray	Pennsylvania
United States	Novo Nordisk Investigational Site	Miami	Florida
United States	Novo Nordisk Investigational Site	Milwaukee	Wisconsin
United States	Novo Nordisk Investigational Site	Monterey	California
United States	Novo Nordisk Investigational Site	Mooresville	North Carolina
United States	Novo Nordisk Investigational Site	Muncie	Indiana
United States	Novo Nordisk Investigational Site	Nashua	New Hampshire
United States	Novo Nordisk Investigational Site	Newport News	Virginia
United States	Novo Nordisk Investigational Site	Norristown	Pennsylvania
United States	Novo Nordisk Investigational Site	Oklahoma City	Oklahoma
United States	Novo Nordisk Investigational Site	Pembroke Pines	Florida
United States	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania
United States	Novo Nordisk Investigational Site	Plantation	Florida
United States	Novo Nordisk Investigational Site	Richmond	Virginia
United States	Novo Nordisk Investigational Site	Richmond	Virginia
United States	Novo Nordisk Investigational Site	Richmond	Virginia
United States	Novo Nordisk Investigational Site	Rockville	Maryland
United States	Novo Nordisk Investigational Site	Rosedale	New York
United States	Novo Nordisk Investigational Site	Roswell	Georgia
United States	Novo Nordisk Investigational Site	Saint Petersburg	Florida
United States	Novo Nordisk Investigational Site	San Diego	California
United States	Novo Nordisk Investigational Site	San Ramon	California
United States	Novo Nordisk Investigational Site	Slidell	Louisiana
United States	Novo Nordisk Investigational Site	Southfield	Michigan
United States	Novo Nordisk Investigational Site	Springfield	Massachusetts
United States	Novo Nordisk Investigational Site	Staten Island	New York
United States	Novo Nordisk Investigational Site	Sugar Land	Texas
United States	Novo Nordisk Investigational Site	Torrance	California
United States	Novo Nordisk Investigational Site	Tustin	California
United States	Novo Nordisk Investigational Site	Ventura	California
United States	Novo Nordisk Investigational Site	Wadsworth	Ohio
United States	Novo Nordisk Investigational Site	Winchester	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  France,  Poland,  Russian Federation,  Ukraine,  United Kingdom, 

References & Publications (2)

Davies MJ, Bain SC, Atkin SL, Rossing P, Scott D, Shamkhalova MS, Bosch-Traberg H, Syrén 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 Impairmen — View 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 Jan 20. doi: 10.1111/dom.1 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Estimated Mean From the Statistical Model and Standard Deviation From Observed Data For Change From Baseline to Week 26 in HbA1c (%) (Glycosylated Haemoglobin)	Calculated as the estimated mean change from baseline in HbA1c (%) after 26 Weeks of treatment based on the statistical model.	Week 0, Week 26
Secondary	Estimated Proportion of Responders Achieving HbA1c <7.0% and no Weight Gain After 26 Weeks of Treatment	Calculated as estimated percentage of subjects achieving HbA1c <7.0% and no weight gain after 26 weeks of treatment based on the statistical model.	At week 26
Secondary	Estimated Proportion of Responders Achieving HbA1c <7.0% and no Minor or Severe Hypoglycaemic Episodes After 26 Weeks of Treatment	Calculated as estimated percentage of subjects achieving HbA1c <7.0% and no minor or severe hypoglycaemic episodes observed within 26 weeks of treatment based on the statistical model.	At week 26
Secondary	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	SMPG was measured before and 90 minutes after breakfast, lunch and dinner and at bedtime at Week 0, 12 and 26. A summary measure of the 7 values was derived for each applicable visit as the area under the curve divided by the period of time elapsed between the first and last measurement. The change from baseline to week 26 was estimated using the statistical model.	Week 0, week 26
Secondary	Estimated Mean From the Statistical Model and Standard Deviation From Observed Data For Change From Baseline to Week 26 in Body Mass Index (BMI)	Calculated as estimated mean change in BMI (kg/m^2) from baseline to Week 26 based on the statistical model.	Week 0, week 26
Secondary	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)	Calculated as the estimated ratio to baseline in eGFR (mL/min/1.73m^2) after 26 Weeks of treatment based on the statistical model.	Week 0, week 26

External Links

•   Clinical Trials at Novo Nordisk