search
Back to results

MARLINA - T2D : Efficacy, Safety & Modification of Albuminuria in Type 2 Diabetes Subjects With Renal Disease With LINAgliptin

Primary Purpose

Diabetes Mellitus, Type 2

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Placebo
Linagliptin 5mg
Sponsored by
Boehringer Ingelheim
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • Diagnosis of type 2 diabetes mellitus
  • Glycosylated Hemoglobin (HbA1c) between 6.5 and 10% (inclusive)
  • Current therapy with ACEi or ARB at stable dose for 10 weeks
  • Urinary albumin-to-creatinine ratio (UACR): 30-3000 mg/g creatinine documented in the previous 12 months or detected at Screening.
  • Estimated Glomerular Filtration Rate (eGFR) greater than 30 ml/min.
  • Age between 18 and 80 years.

Exclusion criteria:

  • Dual or triple blockade of the Renin Angiotensin System (RAS)
  • Uncontrolled hyperglycaemia
  • Mean arterial blood pressure > 110 mmHg
  • Known hypersensitivity or allergy to the investigational product, or their excipients (including matching placebos).
  • Treatment with a glitazone within 6 months prior to informed consent.
  • Treatment with a DiPeptidyl-Peptidase 4 (DPP-4) inhibitor, a Glucagon Like Peptide-1 (GLP-1) agonist, a Sodium/Glucose coTransporter 2 (SGLT2) inhibitor, a dopamine-agonist, a bile-acid sequestrant a short acting (prandial) insulin or premixed insulin within 10 weeks prior to informed consent.
  • Treatment with anti-obesity drugs 10 weeks prior to informed consent.
  • Alcohol or drug abuse within 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake in the opinion of the investigator.
  • Current treatment with systemic steroids (glucocorticoids) at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent.
  • Participation in another trial with an investigational drug within 2 months prior to informed consent.

Sites / Locations

  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

linagliptin 5mg

placebo

Arm Description

linagliptin 5 mg once daily

matching placebo for linagliptin dose once daily

Outcomes

Primary Outcome Measures

HbA1c Change From Baseline After 24 Weeks Double-blind Randomized Treatment
Change from baseline in Glycated haemoglobin (HbA1c) [%] after 24 weeks of treatment with double- blind trial medication. The term "baseline" refers to the last observation before the start of any randomised trial treatment. The number of participants analysed displays the number of participants with available data at the timepoint of interest.

Secondary Outcome Measures

The Time Weighted Average of Percentage Change From Baseline in UACR During the Course of 24 Weeks of Treatment
The time weighted average of percentage change from baseline in UACR (mg/g creatinine) during the course of 24 weeks of treatment. The term "baseline" for UACR refers to the geometric mean of UACR values measured at Visits 2 and 3. The number of participants analysed displays the number of participants with available data at the timepoint of interest. The Least Squares Means are adjusted geometric means.
The Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) After 24 Weeks of Treatment
The change from baseline in estimated glomerular filtration rate (eGFR) as assessed by chronic kidney disease epidemiology collaboration (CKD-EPI) equation (cystatin C) after 24 weeks of treatment. The term "baseline" refers to the last observation before the start of any randomised trial treatment. The number of participants analysed displays the number of participants with available data at the timepoint of interest. This outcome measure is a secondary safety endpoint.

Full Information

First Posted
February 14, 2013
Last Updated
January 13, 2017
Sponsor
Boehringer Ingelheim
Collaborators
Eli Lilly and Company
search

1. Study Identification

Unique Protocol Identification Number
NCT01792518
Brief Title
MARLINA - T2D : Efficacy, Safety & Modification of Albuminuria in Type 2 Diabetes Subjects With Renal Disease With LINAgliptin
Official Title
A Phase IIIb, Multicenter, Multinational, Randomized, Double-blind, Placebo Controlled, Parallel Group Study to Evaluate the Glycemic and Renal Efficacy of Once Daily Administration of Linagliptin 5 mg for 24 Weeks in Type 2 Diabetes Patients, With Micro- or Macroalbuminuria (30-3000mg/g Creatinine) on Top of Current Treatment With Angiotensin ConvEnzyme Inhibitor or Angiotensin Receptor Blocker - MARLINA (Efficacy, Safety & Modification of Albuminuria in Type 2 Diabetes Subjects With Renal Disease With LINAgliptin)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
February 2013 (undefined)
Primary Completion Date
November 2015 (Actual)
Study Completion Date
December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
Collaborators
Eli Lilly and Company

4. Oversight

5. Study Description

Brief Summary
Evaluate linagliptin in terms of glycemic control as defined by HbA1c after 24 weeks of treatment and in terms of renal efficacy as defined by changes in albuminuria (UACR) after 24 weeks of treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
360 (Actual)

8. Arms, Groups, and Interventions

Arm Title
linagliptin 5mg
Arm Type
Experimental
Arm Description
linagliptin 5 mg once daily
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
matching placebo for linagliptin dose once daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Type
Drug
Intervention Name(s)
Linagliptin 5mg
Primary Outcome Measure Information:
Title
HbA1c Change From Baseline After 24 Weeks Double-blind Randomized Treatment
Description
Change from baseline in Glycated haemoglobin (HbA1c) [%] after 24 weeks of treatment with double- blind trial medication. The term "baseline" refers to the last observation before the start of any randomised trial treatment. The number of participants analysed displays the number of participants with available data at the timepoint of interest.
Time Frame
Baseline and 24 weeks
Secondary Outcome Measure Information:
Title
The Time Weighted Average of Percentage Change From Baseline in UACR During the Course of 24 Weeks of Treatment
Description
The time weighted average of percentage change from baseline in UACR (mg/g creatinine) during the course of 24 weeks of treatment. The term "baseline" for UACR refers to the geometric mean of UACR values measured at Visits 2 and 3. The number of participants analysed displays the number of participants with available data at the timepoint of interest. The Least Squares Means are adjusted geometric means.
Time Frame
Baseline and 24 weeks
Title
The Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) After 24 Weeks of Treatment
Description
The change from baseline in estimated glomerular filtration rate (eGFR) as assessed by chronic kidney disease epidemiology collaboration (CKD-EPI) equation (cystatin C) after 24 weeks of treatment. The term "baseline" refers to the last observation before the start of any randomised trial treatment. The number of participants analysed displays the number of participants with available data at the timepoint of interest. This outcome measure is a secondary safety endpoint.
Time Frame
Baseline and 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Diagnosis of type 2 diabetes mellitus Glycosylated Hemoglobin (HbA1c) between 6.5 and 10% (inclusive) Current therapy with ACEi or ARB at stable dose for 10 weeks Urinary albumin-to-creatinine ratio (UACR): 30-3000 mg/g creatinine documented in the previous 12 months or detected at Screening. Estimated Glomerular Filtration Rate (eGFR) greater than 30 ml/min. Age between 18 and 80 years. Exclusion criteria: Dual or triple blockade of the Renin Angiotensin System (RAS) Uncontrolled hyperglycaemia Mean arterial blood pressure > 110 mmHg Known hypersensitivity or allergy to the investigational product, or their excipients (including matching placebos). Treatment with a glitazone within 6 months prior to informed consent. Treatment with a DiPeptidyl-Peptidase 4 (DPP-4) inhibitor, a Glucagon Like Peptide-1 (GLP-1) agonist, a Sodium/Glucose coTransporter 2 (SGLT2) inhibitor, a dopamine-agonist, a bile-acid sequestrant a short acting (prandial) insulin or premixed insulin within 10 weeks prior to informed consent. Treatment with anti-obesity drugs 10 weeks prior to informed consent. Alcohol or drug abuse within 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake in the opinion of the investigator. Current treatment with systemic steroids (glucocorticoids) at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent. Participation in another trial with an investigational drug within 2 months prior to informed consent.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Organizational Affiliation
Boehringer Ingelheim
Official's Role
Study Chair
Facility Information:
Facility Name
Boehringer Ingelheim Investigational Site
City
Birmingham
State/Province
Alabama
Country
United States
Facility Name
Boehringer Ingelheim Investigational Site
City
Long Beach
State/Province
California
Country
United States
Facility Name
Boehringer Ingelheim Investigational Site
City
North Hollywood
State/Province
California
Country
United States
Facility Name
Boehringer Ingelheim Investigational Site
City
Denver
State/Province
Colorado
Country
United States
Facility Name
Boehringer Ingelheim Investigational Site
City
Miami
State/Province
Florida
Country
United States
Facility Name
Boehringer Ingelheim Investigational Site
City
Evansville
State/Province
Indiana
Country
United States
Facility Name
Boehringer Ingelheim Investigational Site
City
Flint
State/Province
Michigan
Country
United States
Facility Name
Boehringer Ingelheim Investigational Site
City
Jackson
State/Province
Mississippi
Country
United States
Facility Name
Boehringer Ingelheim Investigational Site
City
Asheboro
State/Province
North Carolina
Country
United States
Facility Name
Boehringer Ingelheim Investigational Site
City
Charlotte
State/Province
North Carolina
Country
United States
Facility Name
Boehringer Ingelheim Investigational Site
City
Fargo
State/Province
North Dakota
Country
United States
Facility Name
Boehringer Ingelheim Investigational Site
City
Columbus
State/Province
Ohio
Country
United States
Facility Name
Boehringer Ingelheim Investigational Site
City
Oklahoma City
State/Province
Oklahoma
Country
United States
Facility Name
Boehringer Ingelheim Investigational Site
City
Knoxville
State/Province
Tennessee
Country
United States
Facility Name
Boehringer Ingelheim Investigational Site
City
Houston
State/Province
Texas
Country
United States
Facility Name
Boehringer Ingelheim Investigational Site
City
Edmonton
State/Province
Alberta
Country
Canada
Facility Name
Boehringer Ingelheim Investigational Site
City
Victoria
State/Province
British Columbia
Country
Canada
Facility Name
Boehringer Ingelheim Investigational Site
City
Mount Pearl
State/Province
Newfoundland and Labrador
Country
Canada
Facility Name
Boehringer Ingelheim Investigational Site
City
London
State/Province
Ontario
Country
Canada
Facility Name
Boehringer Ingelheim Investigational Site
City
Mississauga
State/Province
Ontario
Country
Canada
Facility Name
Boehringer Ingelheim Investigational Site
City
Sarnia
State/Province
Ontario
Country
Canada
Facility Name
Boehringer Ingelheim Investigational Site
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
Boehringer Ingelheim Investigational Site
City
Waterloo
State/Province
Ontario
Country
Canada
Facility Name
Boehringer Ingelheim Investigational Site
City
Gentofte
Country
Denmark
Facility Name
Boehringer Ingelheim Investigational Site
City
Hillerød
Country
Denmark
Facility Name
Boehringer Ingelheim Investigational Site
City
Silkeborg
Country
Denmark
Facility Name
Boehringer Ingelheim Investigational Site
City
Slagelse
Country
Denmark
Facility Name
Boehringer Ingelheim Investigational Site
City
Kerava
Country
Finland
Facility Name
Boehringer Ingelheim Investigational Site
City
Oulu
Country
Finland
Facility Name
Boehringer Ingelheim Investigational Site
City
Tampere
Country
Finland
Facility Name
Boehringer Ingelheim Investigational Site
City
Turku
Country
Finland
Facility Name
Boehringer Ingelheim Investigational Site
City
Bersée
Country
France
Facility Name
Boehringer Ingelheim Investigational Site
City
Bourg des Comptes
Country
France
Facility Name
Boehringer Ingelheim Investigational Site
City
Grenoble Cedex 09
Country
France
Facility Name
Boehringer Ingelheim Investigational Site
City
Le Creusot
Country
France
Facility Name
Boehringer Ingelheim Investigational Site
City
Marseille cedex
Country
France
Facility Name
Boehringer Ingelheim Investigational Site
City
Saint Mandé cedex
Country
France
Facility Name
Boehringer Ingelheim Investigational Site
City
Vieux Condé
Country
France
Facility Name
Boehringer Ingelheim Investigational Site
City
Vénissieux Cedex
Country
France
Facility Name
Boehringer Ingelheim Investigational Site
City
Aschaffenburg
Country
Germany
Facility Name
Boehringer Ingelheim Investigational Site
City
Asslar
Country
Germany
Facility Name
Boehringer Ingelheim Investigational Site
City
Dresden
Country
Germany
Facility Name
Boehringer Ingelheim Investigational Site
City
Düsseldorf
Country
Germany
Facility Name
Boehringer Ingelheim Investigational Site
City
Flörsheim
Country
Germany
Facility Name
Boehringer Ingelheim Investigational Site
City
Pirna
Country
Germany
Facility Name
Boehringer Ingelheim Investigational Site
City
Schweinfurt
Country
Germany
Facility Name
Boehringer Ingelheim Investigational Site
City
Aoba-ku,Sendai,Miyagi
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Chiyoda-ku,Tokyo
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Cyuo-ku,Tokyo
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Kita-ku, Osaka, Osaka
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Shimizu-ku,Shizuoka city,Shizuoka
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Suita,Osaka
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Teine-ku,Sapporo,Hokkaido
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Goyang
Country
Korea, Republic of
Facility Name
Boehringer Ingelheim Investigational Site
City
Jinju
Country
Korea, Republic of
Facility Name
Boehringer Ingelheim Investigational Site
City
Seongnam
Country
Korea, Republic of
Facility Name
Boehringer Ingelheim Investigational Site
City
Seoul
Country
Korea, Republic of
Facility Name
Boehringer Ingelheim Investigational Site
City
Wonju
Country
Korea, Republic of
Facility Name
Boehringer Ingelheim Investigational Site
City
Cebu City, Philippines
Country
Philippines
Facility Name
Boehringer Ingelheim Investigational Site
City
Pasig City, Philippines
Country
Philippines
Facility Name
Boehringer Ingelheim Investigational Site
City
San Juan City, Philippines
Country
Philippines
Facility Name
Boehringer Ingelheim Investigational Site
City
L'Hospitalet de Llobregat
Country
Spain
Facility Name
Boehringer Ingelheim Investigational Site
City
Madrid
Country
Spain
Facility Name
Boehringer Ingelheim Investigational Site
City
Pozuelo de Alarcon
Country
Spain
Facility Name
Boehringer Ingelheim Investigational Site
City
San Sebastian de los Reyes
Country
Spain
Facility Name
Boehringer Ingelheim Investigational Site
City
Valencia
Country
Spain
Facility Name
Boehringer Ingelheim Investigational Site
City
Changhua
Country
Taiwan
Facility Name
Boehringer Ingelheim Investigational Site
City
Kaohsiung
Country
Taiwan
Facility Name
Boehringer Ingelheim Investigational Site
City
New Taipei
Country
Taiwan
Facility Name
Boehringer Ingelheim Investigational Site
City
Taichung
Country
Taiwan
Facility Name
Boehringer Ingelheim Investigational Site
City
Tainan
Country
Taiwan
Facility Name
Boehringer Ingelheim Investigational Site
City
Taipei
Country
Taiwan
Facility Name
Boehringer Ingelheim Investigational Site
City
Hanoi, Vietnam
Country
Vietnam
Facility Name
Boehringer Ingelheim Investigational Site
City
Ho Chi Minh City
Country
Vietnam

12. IPD Sharing Statement

Citations:
PubMed Identifier
30632692
Citation
Siwy J, Klein T, Rosler M, von Eynatten M. Urinary Proteomics as a Tool to Identify Kidney Responders to Dipeptidyl Peptidase-4 Inhibition: A Hypothesis-Generating Analysis from the MARLINA-T2D Trial. Proteomics Clin Appl. 2019 Mar;13(2):e1800144. doi: 10.1002/prca.201800144. Epub 2019 Jan 28.
Results Reference
derived
PubMed Identifier
28636754
Citation
Groop PH, Cooper ME, Perkovic V, Hocher B, Kanasaki K, Haneda M, Schernthaner G, Sharma K, Stanton RC, Toto R, Cescutti J, Gordat M, Meinicke T, Koitka-Weber A, Thiemann S, von Eynatten M. Linagliptin and its effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction: the randomized MARLINA-T2D trial. Diabetes Obes Metab. 2017 Nov;19(11):1610-1619. doi: 10.1111/dom.13041. Epub 2017 Jul 31.
Results Reference
derived
PubMed Identifier
26224765
Citation
Groop PH, Cooper ME, Perkovic V, Sharma K, Schernthaner G, Haneda M, Hocher B, Gordat M, Cescutti J, Woerle HJ, von Eynatten M. Dipeptidyl peptidase-4 inhibition with linagliptin and effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction: Rationale and design of the MARLINA-T2D trial. Diab Vasc Dis Res. 2015 Nov;12(6):455-62. doi: 10.1177/1479164115579002. Epub 2015 Jul 28.
Results Reference
derived
Links:
URL
http://trials.boehringer-ingelheim.com/
Description
Related Info

Learn more about this trial

MARLINA - T2D : Efficacy, Safety & Modification of Albuminuria in Type 2 Diabetes Subjects With Renal Disease With LINAgliptin

We'll reach out to this number within 24 hrs