Clinical trial NCT01792518: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2013-02-15
Enrollment: 360
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: 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.


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.

Primary outcomes:
measure: HbA1c Change From Baseline After 24 Weeks Double-blind Randomized Treatment
timeFrame: Baseline and 24 weeks
Secondary outcomes:
measure: The Time Weighted Average of Percentage Change From Baseline in UACR During the Course of 24 Weeks of Treatment
timeFrame: Baseline and 24 weeks
measure: The Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) After 24 Weeks of Treatment
timeFrame: Baseline and 24 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Alabama
city: Long Beach
country: United States
facility: Boehringer Ingelheim Investigational Site
state: California
city: North Hollywood
country: United States
facility: Boehringer Ingelheim Investigational Site
state: California
city: Denver
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Colorado
city: Miami
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: Evansville
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Indiana
city: Flint
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Michigan
city: Jackson
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Mississippi
city: Asheboro
country: United States
facility: Boehringer Ingelheim Investigational Site
state: North Carolina
city: Charlotte
country: United States
facility: Boehringer Ingelheim Investigational Site
state: North Carolina
city: Fargo
country: United States
facility: Boehringer Ingelheim Investigational Site
state: North Dakota
city: Columbus
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Oklahoma
city: Knoxville
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Tennessee
city: Houston
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Texas
city: Edmonton
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Alberta
city: Victoria
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: British Columbia
city: Mount Pearl
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Newfoundland and Labrador
city: London
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Mississauga
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Sarnia
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Waterloo
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Gentofte
country: Denmark
facility: Boehringer Ingelheim Investigational Site
city: Hillerød
country: Denmark
facility: Boehringer Ingelheim Investigational Site
city: Silkeborg
country: Denmark
facility: Boehringer Ingelheim Investigational Site
city: Slagelse
country: Denmark
facility: Boehringer Ingelheim Investigational Site
city: Kerava
country: Finland
facility: Boehringer Ingelheim Investigational Site
city: Oulu
country: Finland
facility: Boehringer Ingelheim Investigational Site
city: Tampere
country: Finland
facility: Boehringer Ingelheim Investigational Site
city: Turku
country: Finland
facility: Boehringer Ingelheim Investigational Site
city: Bersée
country: France
facility: Boehringer Ingelheim Investigational Site
city: Bourg des Comptes
country: France
facility: Boehringer Ingelheim Investigational Site
city: Grenoble Cedex 09
country: France
facility: Boehringer Ingelheim Investigational Site
city: Le Creusot
country: France
facility: Boehringer Ingelheim Investigational Site
city: Marseille cedex
country: France
facility: Boehringer Ingelheim Investigational Site
city: Saint Mandé cedex
country: France
facility: Boehringer Ingelheim Investigational Site
city: Vieux Condé
country: France
facility: Boehringer Ingelheim Investigational Site
city: Vénissieux Cedex
country: France
facility: Boehringer Ingelheim Investigational Site
city: Aschaffenburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Asslar
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Dresden
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Düsseldorf
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Flörsheim
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Pirna
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Schweinfurt
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Aoba-ku,Sendai,Miyagi
country: Japan
facility: Boehringer Ingelheim Investigational Site
city: Chiyoda-ku,Tokyo
country: Japan
facility: Boehringer Ingelheim Investigational Site
city: Cyuo-ku,Tokyo
country: Japan
facility: Boehringer Ingelheim Investigational Site
city: Kita-ku, Osaka, Osaka
country: Japan
facility: Boehringer Ingelheim Investigational Site
city: Shimizu-ku,Shizuoka city,Shizuoka
country: Japan
facility: Boehringer Ingelheim Investigational Site
city: Suita,Osaka
country: Japan
facility: Boehringer Ingelheim Investigational Site
city: Teine-ku,Sapporo,Hokkaido
country: Japan
facility: Boehringer Ingelheim Investigational Site
city: Goyang
country: Korea, Republic of
facility: Boehringer Ingelheim Investigational Site
city: Jinju
country: Korea, Republic of
facility: Boehringer Ingelheim Investigational Site
city: Seongnam
country: Korea, Republic of
facility: Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: Boehringer Ingelheim Investigational Site
city: Wonju
country: Korea, Republic of
facility: Boehringer Ingelheim Investigational Site
city: Cebu City, Philippines
country: Philippines
facility: Boehringer Ingelheim Investigational Site
city: Pasig City, Philippines
country: Philippines
facility: Boehringer Ingelheim Investigational Site
city: San Juan City, Philippines
country: Philippines
facility: Boehringer Ingelheim Investigational Site
city: L'Hospitalet de Llobregat
country: Spain
facility: Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: Boehringer Ingelheim Investigational Site
city: Pozuelo de Alarcon
country: Spain
facility: Boehringer Ingelheim Investigational Site
city: San Sebastian de los Reyes
country: Spain
facility: Boehringer Ingelheim Investigational Site
city: Valencia
country: Spain
facility: Boehringer Ingelheim Investigational Site
city: Changhua
country: Taiwan
facility: Boehringer Ingelheim Investigational Site
city: Kaohsiung
country: Taiwan
facility: Boehringer Ingelheim Investigational Site
city: New Taipei
country: Taiwan
facility: Boehringer Ingelheim Investigational Site
city: Taichung
country: Taiwan
facility: Boehringer Ingelheim Investigational Site
city: Tainan
country: Taiwan
facility: Boehringer Ingelheim Investigational Site
city: Taipei
country: Taiwan
facility: Boehringer Ingelheim Investigational Site
city: Hanoi, Vietnam
country: Vietnam
facility: Boehringer Ingelheim Investigational Site
city: Ho Chi Minh City
country: Vietnam
facility: Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
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.
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.
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.