Linagliptin as Add on to Basal Insulin in the Elderly

NCT ID: NCT02240680

Last Updated: 2018-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 302 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-23
• Study Completion Date: 2017-04-25

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.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

linagliptin 5 mg

patient to receive a tablet of linagliptin 5 mg each day

Group Type: EXPERIMENTAL

linagliptin

Intervention Type: DRUG

5 mg once a day

placebo

patient to receive a tablet of placebo matching linagliptin 5 mg

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

placebo matching linagliptin 5 mg

Interventions

placebo

placebo matching linagliptin 5 mg

Intervention Type: DRUG

linagliptin

5 mg once a day

Intervention Type: DRUG

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).

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

Syed Research Consultants, LLC

Sheffield, Alabama, United States

Precision Research Institute, LLC

Chula Vista, California, United States

Aurora Care Clinic, LLC

Costa Mesa, California, United States

Prime Care Clinical Research

Laguna Hills, California, United States

Torrance Clinical Research Institute Inc.

Lomita, California, United States

Internal Medicine of the Rockies

Colorado Springs, Colorado, United States

Cohen Medical Research Associates, LLC

Delray Beach, Florida, United States

Riverside Clinical Research

Edgewater, Florida, United States

Clinical Research of Hollywood

Hollywood, Florida, United States

East Coast Institute for Research LLC at NE FL Endo & Diabetes

Jacksonville, Florida, United States

Solutions Through Advanced Research, Inc.

Jacksonville, Florida, United States

Baptist Diabetes Associates, PA

Miami, Florida, United States

International Research Associates

Miami, Florida, United States

Panax Clinical Research

Miami Lakes, Florida, United States

South Florida Research Solutions, LLC

Pembroke Pines, Florida, United States

Georgia Clinical Research, LLC

Snellville, Georgia, United States

Midwest Endocrinology

Crystal Lake, Illinois, United States

American Health Network

Avon, Indiana, United States

Accent Clinical Trials

Las Vegas, Nevada, United States

Clinical Research of South Nevada

Las Vegas, Nevada, United States

Manhattan Medical Research Practice PLLC

New York, New York, United States

Family Practice Center of Wadsworth, Inc.

Wadsworth, Ohio, United States

Clinical Research Associates of Central Pennsylvania

Altoona, Pennsylvania, United States

Fleetwood Clinical Research

Fleetwood, Pennsylvania, United States

Preferred Primary Care Phys

Uniontown, Pennsylvania, United States

TLM Medical Services, LLC

Columbia, South Carolina, United States

Advanced Research Associates

Hodges, South Carolina, United States

Holston Medical Group

Kingsport, Tennessee, United States

Arlington Family Research Center, Inc.

Arlington, Texas, United States

Renaissance Clinical Research and Hypertension of Texas

Dallas, Texas, United States

Diabetes and Thyroid Center of Fort Worth

Fort Worth, Texas, United States

Houston Clinical Research Associates

Houston, Texas, United States

Science Advancing Medicine Clinical Research Center

San Antonio, Texas, United States

Office of Dr. Val R. Hansen

Bountiful, Utah, United States

Millennium Clinical Trials LLC

Arlington, Virginia, United States

York Clinical Research, LLC

Norfolk, Virginia, United States

Rowan Research, Inc.

Spokane, Washington, United States

Family Medical Clinic

Milwaukee, Wisconsin, United States

AIM Centre

Merewether, New South Wales, Australia

Royal Brisbane & Women's Hospital-Endocrinology

Herston, Queensland, Australia

ECRU Maroondah

East Ringwood, Victoria, Australia

Ham - PRAC Mortelmans

Oostham, , Belgium

CEQUIN

Armenia, , Colombia

Dexa Diabetes Servicios Médicos Ltda

Bogotá, , Colombia

CAFAM Caja de Compensación Familiar

Bogotá, , Colombia

Asociacion IPS Medicos Internistas de Caldas

Manizales, , Colombia

Hospital Pablo Tobón Uribe

Medellín, , Colombia

Aalborg Sygehus Syd

Aalborg, , Denmark

Sydvestjyst Sygehus Esbjerg, Endokrinologisk afdeling

Esbjerg, , Denmark

Frederiksberg Hospital, Endokrinologisk afd.

Frederiksberg, , Denmark

Gentofte University Hospital

Hellerup, , Denmark

Kolding Sygehus

Kolding, , Denmark

Bispebjerg Hospital

København NV, , Denmark

Køge Sygehus

Køge, , Denmark

Roskilde Sygehus

Roskilde, , Denmark

Keravan terveyskeskus

Kerava, , Finland

Terveystalo Oulu, Diapolis

Oulu, , Finland

Lääkärikeskus Aava, Turku

Turku, , Finland

TYKS

Turku, , Finland

Gemeinschaftspraxis, Asslar

Aßlar, , Germany

ikfe - Institut für klinische Forschung und Entwicklung Berlin GmbH

Berlin, , Germany

Diabetologische Schwerpunktpraxis, Bosenheim

Bosenheim, , Germany

Dünnwaldpraxis, Köln

Cologne, , Germany

Praxis Dr. Naudts, Rodgau

Rodgau, , Germany

Praxis Dr. Braun, Unterschneidheim

Unterschneidheim, , Germany

"Korgialeneio-Benakeio" Hellenic Red Cross Hospital

Athens, , Greece

General Hospital of Athens "G. Gennimatas"

Athens, , Greece

Univ. Gen. Hosp. of Ioannina

Ioannina, , Greece

General Hospital of Attiki "KAT-EKA"

Kifissia, , Greece

General Hospital of Nikaia

Nikaia, , Greece

General Hospital of Thessaloniki "G. Papanikolaou"

Thessaloniki, , Greece

Connolly Hospital Blanchardstown

Dublin, , Ireland

Daishinkai Medical Corporation Ookuma Hospital

Aichi, Nagoya, , Japan

Matsuyama Shimin Hospital

Ehime, Matsuyama, , Japan

Iryohojin Kikuchi Naika Clinic

Gunma, Maebashi, , Japan

Nakamura Digestive Organ Internal Medicine Clinic

Hokkaido, Bibai, , Japan

Iida Medical Clinic

Hokkaido, Hakodate, , Japan

Jiyugaoka Yamada Clinic

Hokkaido, Obihiro, , Japan

Shinkotoni family Clinic

Hokkaido, Sapporo, , Japan

Yoshida Memorial Hospital

Hokkaido, Sapporo, , Japan

Teine Keijinkai Clinic

Hokkaido, Sapporo, , Japan

Japan Community Health Care Organization Hokkaido Hospital

Hokkaido, Sapporo, , Japan

Itabashi Diabetic medicine and Dermatology Clinic

Ibaraki, Koga, , Japan

Nakakinen Clinic

Ibaraki, Naka, , Japan

Takai Naika Clinic

Kanagawa, Kamakura, , Japan

Kaneshiro DIAB Clinic, Kanagawa, I.M.

Kanagawa, Sagamihara, , Japan

Asahi Med. clinic, Kanagawa, I.M.

Kanagawa, Yokohama, , Japan

Ishikawa Med. Clinic, Kanagawa, I.M.

Kanagawa, Yokohama, , Japan

National Hospital Organization Yokohama Medical Center

Kanagawa, Yokohama, , Japan

Okayama Saiseikai General Hospital Outpatient Center

Okayama, Okayama, , Japan

AMC Nishi-umeda Clinic

Osaka, Osaka, , Japan

Nissay Hospital Nippon Life Saiseikai Public Interest Incorporated Foundation

Osaka, Osaka, , Japan

OCROM Clinic

Osaka, Suita, , Japan

Saga Memorial Hospital

Saga, Saga, , Japan

Asano Clinic

Saitama, Kawagoe, , Japan

Hamamatsu Rosai Hospital

Shizuoka, Hamamatsu, , Japan

Kuriyama Clinic

Tokyo, Adachi-ku, , Japan

The Institute for Adult Deseases, Asahi Life Foundation

Tokyo, Chuo-ku, , Japan

Tokyo-Eki Center-building Clinic

Tokyo, Chuo-ku, , Japan

Tokyo Center Clinic

Tokyo, Chuo-ku, , Japan

AGE Makita Medical Clinic

Tokyo, Chuo-ku, , Japan

Kobayashi Internal Medicine Clinic

Tokyo, Koto-ku, , Japan

Kunitachi Naika Clinic

Tokyo, Kunitachi, , Japan

Japanese Red Cross Medical Center

Tokyo, Shibuya-ku, , Japan

Investigación en Salud y Metabolismo S.C.

Chihuahua City, , Mexico

Centro de At. e Inv.en Fact.de riesgo cardiovasc.Omega, S.C.

México, , Mexico

Clinstile S.A. de C.V.

México, , Mexico

CAIMED

México, , Mexico

CEDOPEC-Ctro Esp en Diab, Obesidad y Prev de Enf Cardiovasc

México, , Mexico

Asociación Mexicana para la Investigacion Clínica, A.C(AMIC)

Pachuca, , Mexico

Middlemore Clinical Trials

Auckland, , New Zealand

South Pacific Clinical Trials

Auckland, New Zealand, , New Zealand

Christchurch Hospital

Christchurch, , New Zealand

Medicome Sp. z o.o.

Oświęcim, , Poland

Omedica Centrum Medyczne

Poznan, , Poland

NBR Polska

Warsaw, , Poland

Nicodiab SRL, Bucharest

Bucharest, , Romania

Pelican Impex SRL, Cabinet Nr. 15

Oradea, , Romania

Mediab SRL

Târgu Mureş, , Romania

TREAD Research

Cape Town, , South Africa

Tiervlei Trial Centre

Cape Town, , South Africa

Paarl Research Centre

Cape Town, , South Africa

Soweto Clinical Trials Centre

Johannesburg, , South Africa

LCS Clinical Research Unit

Johannesburg, , South Africa

Resego Health Services

Johannesburg, , South Africa

Zinakekele Medical Centre

Kwamhlanga, , South Africa

Mzansi Ethical Research Centre

Middleburg, , South Africa

VX Pharma (Pty) Ltd Pretoria

Pretoria, , South Africa

Hospital A Coruña

A Coruña, , Spain

Instituto de Ciencias Médicas

Alicante, , Spain

Hospital Quiron. I.C.U.

Barcelona, , Spain

C.A.P. Sardenya

Barcelona, , Spain

CAP Les Corts

Barcelona, , Spain

CAP Canet de Mar

Canet de Mar, , Spain

Hospital Virgen de la Victoria

Málaga, , Spain

Hospital Nuestra Señora de Valme

Seville, , Spain

Hospital Clínico de Valencia

Valencia, , Spain

CAP El Remei

Vic, , Spain

The Haven Surgery

Burnhope, , United Kingdom

South Axholme Practice

Doncaster, , United Kingdom

Fowey Clinical Research Company Ltd

Fowey, , United Kingdom

Oak Tree Surgery

Liskeard, , United Kingdom

St. Mary's Hospital, Vectasearch Clinic, Newport

Newport, , United Kingdom

Mounts Bay Medical Ltd

Penzance, , United Kingdom

Rame Medical, Penntorr Health

Torpoint, , United Kingdom

Countries

United States; Australia; Belgium; Colombia; Denmark; Finland; Germany; Greece; Ireland; Japan; Mexico; New Zealand; Poland; Romania; South Africa; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 31482511 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2014-000904-88

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1218.149

Identifier Type: -

Identifier Source: org_study_id