Clinical trial NCT02240680: Linagliptin as Add on to Basal Insulin in the Elderly
Official title: A 24 Week Randomized, Double-blind, Placebo-controlled, Parallel Group, Efficacy and Safety Trial of Once Daily Linagliptin, 5 Milligrams Orally, as Add on to Basal Insulin in Elderly Type 2 Diabetes Mellitus Patients With Insufficient Glycaemic Control
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2014-09-16
Enrollment: 302
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To investigate the efficacy, safety, and tolerability of linagliptin 5 milligrams once a day compared to placebo as as add-on therapy for 24 weeks to stable basal insulin treatment in elderly patients, 60 years of age and older, with Type 2 Diabetes Mellitus and insufficient glycaemic control.Stable background therapy of metformin and/or alpha-glucosidase inhibitors is also allowed.

In addition, this trial will assess if linagliptin reduces the risk of hypoglycaemia when added to background basal insulin therapy. The treatment duration of this trial (24 weeks) will enable assessment of the clinically relevant endpoint of a decrease in glycosylated Haemoglobin, a well-accepted measurement of chronic glycaemic control.


Eligibility criteria: Inclusion criteria:

* Patients must sign and date an Informed Consent consistent with International Conference on Harmonisation and Good Clinical Practice guidelines and local regulations prior to any evaluation and participation in the trial.
* Male and female patients with a clinical diagnosis of Type 2 Diabetes Mellitus, at the time of Informed Consent, who are:
* 60 years of age or older at informed consent or Screen Visit,
* taking stable doses of basal or biosimilar basal insulin \[strictly inclusive of: insulin neutral protamine Hagedorn and isophane insulin; Humalog Basal (a suspension of insulin lispro protamine); insulin degludec; insulin detemir; and insulin glargine\] for at least 4 weeks prior to randomisation (Visit 3) with dose adjustments up to a maximum of plus or minus 20% of baseline being allowed,
* may or may not be taking metformin immediate release or extended release \[if the patient is taking metformin, stable dose must be maintained for at least twelve weeks without dose adjustments prior to randomisation (Visit 3)\], and
* may or may not be taking alpha-glucosidase inhibitors \[acarbose, miglitol, and voglibose; if the patient is taking alpha-glucosidase inhibitors, stable dose must be maintained for at least twelve weeks without dose adjustments prior to randomisation (Visit 3)\].
* Patients must have an glycosylated Haemoglobin of 7.0% (53 millimoles per mole) to 10.0% (86 millimoles per mole) at the first visit (Screen).
* Patients must have a Body Mass Index of 45 kilogram/meter squared or less at the Screen Visit.
* In the investigator's opinion, patients must be reliable, compliant, and agree to cooperate with all planned future trial evaluations as explained in detail during the informed consent process and to be able to perform them.

Exclusion criteria:

* Impaired cognitive ability as supported by the Saint Louis University Mental Status Examination, additional assessment if necessary, and verified by the investigator at the Screen Visit.
* Depressed mood as supported by a score of 10 or more on the Patient Health Questionnaire at the Screen Visit.
* Type 1 Diabetes Mellitus as determined by past medical records and history.
* Acute coronary syndrome (non-ST Elevation Myocardial Infarction, ST Elevation Myocardial Infarction, and/or unstable angina pectoris), stroke or transient ischemic attack within 3 months prior to Screen Visit.
* Indication of liver disease determined during Screen and/or Run-In Period, defined by a serum level above 3 times the upper limit of normal in any of the following: alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase.
* Bariatric, gastric bypass, and other gastrointestinal procedures or surgeries (including all types of gastric banding, restriction, and/or LapBand) with the objective of promoting weight loss within the past two years at Screen Visit.
* Medical history of cancer (except for resected non-invasive basal or squamous cell carcinoma) and/or treatment for cancer within the last 5 years.
* Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells (malaria, babesiosis, haemolytic anaemia).

Primary outcomes:
measure: Change From Baseline in Hemoglobin A1c (HbA1c) After 24 Weeks of Treatment.
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Percentage of Patients Experiencing at Least One Hypoglycaemia Accompanied by a Prespecified Glucose Value.
timeFrame: 24 weeks
measure: Percentage of Patients With HbA1c<8.0%
timeFrame: 24 weeks
measure: Percentage of Patients With HbA1c on Treatment <7.0%
timeFrame: 24 weeks
measure: Percentage of Patients With HbA1c Lowering by at Least 0.5%.
timeFrame: 24 weeks
measure: Change From Baseline in Fasting Plasma Glucose (FPG)
timeFrame: Baseline and Week 24
Other outcomes:
Locations:
city: Sheffield
country: United States
facility: Syed Research Consultants, LLC
state: Alabama
city: Chula Vista
country: United States
facility: Precision Research Institute, LLC
state: California
city: Costa Mesa
country: United States
facility: Aurora Care Clinic, LLC
state: California
city: Laguna Hills
country: United States
facility: Prime Care Clinical Research
state: California
city: Lomita
country: United States
facility: Torrance Clinical Research Institute Inc.
state: California
city: Colorado Springs
country: United States
facility: Internal Medicine of the Rockies
state: Colorado
city: Delray Beach
country: United States
facility: Cohen Medical Research Associates, LLC
state: Florida
city: Edgewater
country: United States
facility: Riverside Clinical Research
state: Florida
city: Hollywood
country: United States
facility: Clinical Research of Hollywood
state: Florida
city: Jacksonville
country: United States
facility: East Coast Institute for Research LLC at NE FL Endo & Diabetes
state: Florida
city: Jacksonville
country: United States
facility: Solutions Through Advanced Research, Inc.
state: Florida
city: Miami Lakes
country: United States
facility: Panax Clinical Research
state: Florida
city: Miami
country: United States
facility: Baptist Diabetes Associates, PA
state: Florida
city: Miami
country: United States
facility: International Research Associates
state: Florida
city: Pembroke Pines
country: United States
facility: South Florida Research Solutions, LLC
state: Florida
city: Snellville
country: United States
facility: Georgia Clinical Research, LLC
state: Georgia
city: Crystal Lake
country: United States
facility: Midwest Endocrinology
state: Illinois
city: Avon
country: United States
facility: American Health Network
state: Indiana
city: Las Vegas
country: United States
facility: Accent Clinical Trials
state: Nevada
city: Las Vegas
country: United States
facility: Clinical Research of South Nevada
state: Nevada
city: New York
country: United States
facility: Manhattan Medical Research Practice PLLC
state: New York
city: Wadsworth
country: United States
facility: Family Practice Center of Wadsworth, Inc.
state: Ohio
city: Altoona
country: United States
facility: Clinical Research Associates of Central Pennsylvania
state: Pennsylvania
city: Fleetwood
country: United States
facility: Fleetwood Clinical Research
state: Pennsylvania
city: Uniontown
country: United States
facility: Preferred Primary Care Phys
state: Pennsylvania
city: Columbia
country: United States
facility: TLM Medical Services, LLC
state: South Carolina
city: Hodges
country: United States
facility: Advanced Research Associates
state: South Carolina
city: Kingsport
country: United States
facility: Holston Medical Group
state: Tennessee
city: Arlington
country: United States
facility: Arlington Family Research Center, Inc.
state: Texas
city: Dallas
country: United States
facility: Renaissance Clinical Research and Hypertension of Texas
state: Texas
city: Fort Worth
country: United States
facility: Diabetes and Thyroid Center of Fort Worth
state: Texas
city: Houston
country: United States
facility: Houston Clinical Research Associates
state: Texas
city: San Antonio
country: United States
facility: Science Advancing Medicine Clinical Research Center
state: Texas
city: Bountiful
country: United States
facility: Office of Dr. Val R. Hansen
state: Utah
city: Arlington
country: United States
facility: Millennium Clinical Trials LLC
state: Virginia
city: Norfolk
country: United States
facility: York Clinical Research, LLC
state: Virginia
city: Spokane
country: United States
facility: Rowan Research, Inc.
state: Washington
city: Milwaukee
country: United States
facility: Family Medical Clinic
state: Wisconsin
city: Merewether
country: Australia
facility: AIM Centre
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane & Women's Hospital-Endocrinology
state: Queensland
city: East Ringwood
country: Australia
facility: ECRU Maroondah
state: Victoria
city: Oostham
country: Belgium
facility: Ham - PRAC Mortelmans
city: Armenia
country: Colombia
facility: CEQUIN
city: Bogotá
country: Colombia
facility: Dexa Diabetes Servicios Médicos Ltda
city: Bogotá
country: Colombia
facility: CAFAM Caja de Compensación Familiar
city: Manizales
country: Colombia
facility: Asociacion IPS Medicos Internistas de Caldas
city: Medellín
country: Colombia
facility: Hospital Pablo Tobón Uribe
city: Aalborg
country: Denmark
facility: Aalborg Sygehus Syd
city: Esbjerg
country: Denmark
facility: Sydvestjyst Sygehus Esbjerg, Endokrinologisk afdeling
city: Frederiksberg
country: Denmark
facility: Frederiksberg Hospital, Endokrinologisk afd.
city: Hellerup
country: Denmark
facility: Gentofte University Hospital
city: Kolding
country: Denmark
facility: Kolding Sygehus
city: København NV
country: Denmark
facility: Bispebjerg Hospital
city: Køge
country: Denmark
facility: Køge Sygehus
city: Roskilde
country: Denmark
facility: Roskilde Sygehus
city: Kerava
country: Finland
facility: Keravan terveyskeskus
city: Oulu
country: Finland
facility: Terveystalo Oulu, Diapolis
city: Turku
country: Finland
facility: Lääkärikeskus Aava, Turku
city: Turku
country: Finland
facility: TYKS
city: Asslar
country: Germany
facility: Gemeinschaftspraxis, Asslar
city: Berlin
country: Germany
facility: ikfe - Institut für klinische Forschung und Entwicklung Berlin GmbH
city: Bosenheim
country: Germany
facility: Diabetologische Schwerpunktpraxis, Bosenheim
city: Koeln
country: Germany
facility: Dünnwaldpraxis, Köln
city: Rodgau
country: Germany
facility: Praxis Dr. Naudts, Rodgau
city: Unterschneidheim
country: Germany
facility: Praxis Dr. Braun, Unterschneidheim
city: Athens
country: Greece
facility: "Korgialeneio-Benakeio" Hellenic Red Cross Hospital
city: Athens
country: Greece
facility: General Hospital of Athens "G. Gennimatas"
city: Ioannina
country: Greece
facility: Univ. Gen. Hosp. of Ioannina
city: Kifisia
country: Greece
facility: General Hospital of Attiki "KAT-EKA"
city: Nikaia
country: Greece
facility: General Hospital of Nikaia
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki "G. Papanikolaou"
city: Dublin
country: Ireland
facility: Connolly Hospital Blanchardstown
city: Aichi, Nagoya
country: Japan
facility: Daishinkai Medical Corporation Ookuma Hospital
city: Ehime, Matsuyama
country: Japan
facility: Matsuyama Shimin Hospital
city: Gunma, Maebashi
country: Japan
facility: Iryohojin Kikuchi Naika Clinic
city: Hokkaido, Bibai
country: Japan
facility: Nakamura Digestive Organ Internal Medicine Clinic
city: Hokkaido, Hakodate
country: Japan
facility: Iida Medical Clinic
city: Hokkaido, Obihiro
country: Japan
facility: Jiyugaoka Yamada Clinic
city: Hokkaido, Sapporo
country: Japan
facility: Shinkotoni family Clinic
city: Hokkaido, Sapporo
country: Japan
facility: Yoshida Memorial Hospital
city: Hokkaido, Sapporo
country: Japan
facility: Teine Keijinkai Clinic
city: Hokkaido, Sapporo
country: Japan
facility: Japan Community Health Care Organization Hokkaido Hospital
city: Ibaraki, Koga
country: Japan
facility: Itabashi Diabetic medicine and Dermatology Clinic
city: Ibaraki, Naka
country: Japan
facility: Nakakinen Clinic
city: Kanagawa, Kamakura
country: Japan
facility: Takai Naika Clinic
city: Kanagawa, Sagamihara
country: Japan
facility: Kaneshiro DIAB Clinic, Kanagawa, I.M.
city: Kanagawa, Yokohama
country: Japan
facility: Asahi Med. clinic, Kanagawa, I.M.
city: Kanagawa, Yokohama
country: Japan
facility: Ishikawa Med. Clinic, Kanagawa, I.M.
city: Kanagawa, Yokohama
country: Japan
facility: National Hospital Organization Yokohama Medical Center
city: Okayama, Okayama
country: Japan
facility: Okayama Saiseikai General Hospital Outpatient Center
city: Osaka, Osaka
country: Japan
facility: AMC Nishi-umeda Clinic
city: Osaka, Osaka
country: Japan
facility: Nissay Hospital Nippon Life Saiseikai Public Interest Incorporated Foundation
city: Osaka, Suita
country: Japan
facility: OCROM Clinic
city: Saga, Saga
country: Japan
facility: Saga Memorial Hospital
city: Saitama, Kawagoe
country: Japan
facility: Asano Clinic
city: Shizuoka, Hamamatsu
country: Japan
facility: Hamamatsu Rosai Hospital
city: Tokyo, Adachi-ku
country: Japan
facility: Kuriyama Clinic
city: Tokyo, Chuo-ku
country: Japan
facility: The Institute for Adult Deseases, Asahi Life Foundation
city: Tokyo, Chuo-ku
country: Japan
facility: Tokyo-Eki Center-building Clinic
city: Tokyo, Chuo-ku
country: Japan
facility: Tokyo Center Clinic
city: Tokyo, Chuo-ku
country: Japan
facility: AGE Makita Medical Clinic
city: Tokyo, Koto-ku
country: Japan
facility: Kobayashi Internal Medicine Clinic
city: Tokyo, Kunitachi
country: Japan
facility: Kunitachi Naika Clinic
city: Tokyo, Shibuya-ku
country: Japan
facility: Japanese Red Cross Medical Center
city: Chihuahua
country: Mexico
facility: Investigación en Salud y Metabolismo S.C.
city: Mexico
country: Mexico
facility: Centro de At. e Inv.en Fact.de riesgo cardiovasc.Omega, S.C.
city: Mexico
country: Mexico
facility: CAIMED
city: México
country: Mexico
facility: Clinstile S.A. de C.V.
city: México
country: Mexico
facility: CEDOPEC-Ctro Esp en Diab, Obesidad y Prev de Enf Cardiovasc
city: Pachuca
country: Mexico
facility: Asociación Mexicana para la Investigacion Clínica, A.C(AMIC)
city: Auckland, New Zealand
country: New Zealand
facility: South Pacific Clinical Trials
city: Auckland
country: New Zealand
facility: Middlemore Clinical Trials
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Oswiecim
country: Poland
facility: Medicome Sp. z o.o.
city: Poznan
country: Poland
facility: Omedica Centrum Medyczne
city: Warszawa
country: Poland
facility: NBR Polska
city: Bucharest
country: Romania
facility: Nicodiab SRL, Bucharest
city: Oradea
country: Romania
facility: Pelican Impex SRL, Cabinet Nr. 15
city: Tirgu Mures
country: Romania
facility: Mediab SRL
city: Cape Town
country: South Africa
facility: TREAD Research
city: Cape Town
country: South Africa
facility: Tiervlei Trial Centre
city: Cape Town
country: South Africa
facility: Paarl Research Centre
city: Johannesburg
country: South Africa
facility: Soweto Clinical Trials Centre
city: Johannesburg
country: South Africa
facility: LCS Clinical Research Unit
city: Johannesburg
country: South Africa
facility: Resego Health Services
city: KwaMhlanga
country: South Africa
facility: Zinakekele Medical Centre
city: Middleburg
country: South Africa
facility: Mzansi Ethical Research Centre
city: Pretoria
country: South Africa
facility: VX Pharma (Pty) Ltd Pretoria
city: A Coruña
country: Spain
facility: Hospital A Coruña
city: Alicante
country: Spain
facility: Instituto de Ciencias Médicas
city: Barcelona
country: Spain
facility: Hospital Quiron. I.C.U.
city: Barcelona
country: Spain
facility: C.A.P. Sardenya
city: Barcelona
country: Spain
facility: CAP Les Corts
city: Canet de Mar
country: Spain
facility: CAP Canet de Mar
city: Malaga
country: Spain
facility: Hospital Virgen de la Victoria
city: Sevilla
country: Spain
facility: Hospital Nuestra Señora de Valme
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia
city: Vic
country: Spain
facility: CAP El Remei
city: Burnhope
country: United Kingdom
facility: The Haven Surgery
city: Doncaster
country: United Kingdom
facility: South Axholme Practice
city: Fowey
country: United Kingdom
facility: Fowey Clinical Research Company Ltd
city: Liskeard
country: United Kingdom
facility: Oak Tree Surgery
city: Newport
country: United Kingdom
facility: St. Mary's Hospital, Vectasearch Clinic, Newport
city: Penzance
country: United Kingdom
facility: Mounts Bay Medical Ltd
city: Torpoint
country: United Kingdom
facility: Rame Medical, Penntorr Health
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Araki E, Unno Y, Tanaka Y, Sakamoto W, Miyamoto Y. Long-Term Efficacy and Safety of Linagliptin in a Japanese Population with Type 2 Diabetes Aged >/= 60 Years Treated with Basal Insulin: A Randomised Trial. Adv Ther. 2019 Oct;36(10):2697-2711. doi: 10.1007/s12325-019-01065-7. Epub 2019 Sep 3.