Linagliptin as Add on to Basal Insulin in the Elderly

Diabetes Mellitus, Type 2 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02240680
• Other study ID #: 1218.149
• Secondary ID: 2014-000904-88
• Status: Completed
• Phase: Phase 4
• Start date: September 23, 2014
• Est. completion date: April 25, 2017

Study information

• Verified date: May 2018
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 302
• Est. completion date: April 25, 2017
• Est. primary completion date: April 18, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• placebo
placebo matching linagliptin 5 mg
• linagliptin
5 mg once a day

Locations

Country	Name	City	State
Australia	ECRU Maroondah	East Ringwood	Victoria
Australia	Royal Brisbane & Women's Hospital-Endocrinology	Herston	Queensland
Australia	AIM Centre	Merewether	New South Wales
Belgium	Ham - PRAC Mortelmans	Oostham
Colombia	CEQUIN	Armenia
Colombia	CAFAM Caja de Compensación Familiar	Bogotá
Colombia	Dexa Diabetes Servicios Médicos Ltda	Bogotá
Colombia	Asociacion IPS Medicos Internistas de Caldas	Manizales
Colombia	Hospital Pablo Tobón Uribe	Medellín
Denmark	Aalborg Sygehus Syd	Aalborg
Denmark	Sydvestjyst Sygehus Esbjerg, Endokrinologisk afdeling	Esbjerg
Denmark	Frederiksberg Hospital, Endokrinologisk afd.	Frederiksberg
Denmark	Gentofte University Hospital	Hellerup
Denmark	Bispebjerg Hospital	København NV
Denmark	Køge Sygehus	Køge
Denmark	Kolding Sygehus	Kolding
Denmark	Roskilde Sygehus	Roskilde
Finland	Keravan terveyskeskus	Kerava
Finland	Terveystalo Oulu, Diapolis	Oulu
Finland	Lääkärikeskus Aava, Turku	Turku
Finland	TYKS	Turku
Germany	Gemeinschaftspraxis, Asslar	Asslar
Germany	ikfe - Institut für klinische Forschung und Entwicklung Berlin GmbH	Berlin
Germany	Diabetologische Schwerpunktpraxis, Bosenheim	Bosenheim
Germany	Dünnwaldpraxis, Köln	Koeln
Germany	Praxis Dr. Naudts, Rodgau	Rodgau
Germany	Praxis Dr. Braun, Unterschneidheim	Unterschneidheim
Greece	"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"	Kifisia
Greece	General Hospital of Nikaia	Nikaia
Greece	General Hospital of Thessaloniki "G. Papanikolaou"	Thessaloniki
Ireland	Connolly Hospital Blanchardstown	Dublin
Japan	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	Japan Community Health Care Organization Hokkaido Hospital	Hokkaido, Sapporo
Japan	Shinkotoni family Clinic	Hokkaido, Sapporo
Japan	Teine Keijinkai Clinic	Hokkaido, Sapporo
Japan	Yoshida Memorial 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	AGE Makita Medical Clinic	Tokyo, Chuo-ku
Japan	The Institute for Adult Deseases, Asahi Life Foundation	Tokyo, Chuo-ku
Japan	Tokyo Center Clinic	Tokyo, Chuo-ku
Japan	Tokyo-Eki Center-building 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
Mexico	Investigación en Salud y Metabolismo S.C.	Chihuahua
Mexico	CAIMED	Mexico
Mexico	Centro de At. e Inv.en Fact.de riesgo cardiovasc.Omega, S.C.	Mexico
Mexico	CEDOPEC-Ctro Esp en Diab, Obesidad y Prev de Enf Cardiovasc	México
Mexico	Clinstile S.A. de C.V.	México
Mexico	Asociación Mexicana para la Investigacion Clínica, A.C(AMIC)	Pachuca
New Zealand	Middlemore Clinical Trials	Auckland
New Zealand	South Pacific Clinical Trials	Auckland, New Zealand
New Zealand	Christchurch Hospital	Christchurch
Poland	Medicome Sp. z o.o.	Oswiecim
Poland	Omedica Centrum Medyczne	Poznan
Poland	NBR Polska	Warszawa
Romania	Nicodiab SRL, Bucharest	Bucharest
Romania	Pelican Impex SRL, Cabinet Nr. 15	Oradea
Romania	Mediab SRL	Tirgu Mures
South Africa	Paarl Research Centre	Cape Town
South Africa	Tiervlei Trial Centre	Cape Town
South Africa	TREAD Research	Cape Town
South Africa	LCS Clinical Research Unit	Johannesburg
South Africa	Resego Health Services	Johannesburg
South Africa	Soweto Clinical Trials Centre	Johannesburg
South Africa	Zinakekele Medical Centre	KwaMhlanga
South Africa	Mzansi Ethical Research Centre	Middleburg
South Africa	VX Pharma (Pty) Ltd Pretoria	Pretoria
Spain	Hospital A Coruña	A Coruña
Spain	Instituto de Ciencias Médicas	Alicante
Spain	C.A.P. Sardenya	Barcelona
Spain	CAP Les Corts	Barcelona
Spain	Hospital Quiron. I.C.U.	Barcelona
Spain	CAP Canet de Mar	Canet de Mar
Spain	Hospital Virgen de la Victoria	Malaga
Spain	Hospital Nuestra Señora de Valme	Sevilla
Spain	Hospital Clínico de Valencia	Valencia
Spain	CAP El Remei	Vic
United Kingdom	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 States	Clinical Research Associates of Central Pennsylvania	Altoona	Pennsylvania
United States	Arlington Family Research Center, Inc.	Arlington	Texas
United States	Millennium Clinical Trials LLC	Arlington	Virginia
United States	American Health Network	Avon	Indiana
United States	Office of Dr. Val R. Hansen	Bountiful	Utah
United States	Precision Research Institute, LLC	Chula Vista	California
United States	Internal Medicine of the Rockies	Colorado Springs	Colorado
United States	TLM Medical Services, LLC	Columbia	South Carolina
United States	Aurora Care Clinic, LLC	Costa Mesa	California
United States	Midwest Endocrinology	Crystal Lake	Illinois
United States	Renaissance Clinical Research and Hypertension of Texas	Dallas	Texas
United States	Cohen Medical Research Associates, LLC	Delray Beach	Florida
United States	Riverside Clinical Research	Edgewater	Florida
United States	Fleetwood Clinical Research	Fleetwood	Pennsylvania
United States	Diabetes and Thyroid Center of Fort Worth	Fort Worth	Texas
United States	Advanced Research Associates	Hodges	South Carolina
United States	Clinical Research of Hollywood	Hollywood	Florida
United States	Houston Clinical Research Associates	Houston	Texas
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	Holston Medical Group	Kingsport	Tennessee
United States	Prime Care Clinical Research	Laguna Hills	California
United States	Accent Clinical Trials	Las Vegas	Nevada
United States	Clinical Research of South Nevada	Las Vegas	Nevada
United States	Torrance Clinical Research Institute Inc.	Lomita	California
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	Family Medical Clinic	Milwaukee	Wisconsin
United States	Manhattan Medical Research Practice PLLC	New York	New York
United States	York Clinical Research, LLC	Norfolk	Virginia
United States	South Florida Research Solutions, LLC	Pembroke Pines	Florida
United States	Science Advancing Medicine Clinical Research Center	San Antonio	Texas
United States	Syed Research Consultants, LLC	Sheffield	Alabama
United States	Georgia Clinical Research, LLC	Snellville	Georgia
United States	Rowan Research, Inc.	Spokane	Washington
United States	Preferred Primary Care Phys	Uniontown	Pennsylvania
United States	Family Practice Center of Wadsworth, Inc.	Wadsworth	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Boehringer Ingelheim	Eli Lilly and Company

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Hemoglobin A1c (HbA1c) After 24 Weeks of Treatment.	This outcome has measured difference between HbA1c values from baseline to 24 weeks post treatment. The term 'baseline' refers to the last observation prior to the administration of any randomised study medication. HbA1c is a form of hemoglobin, a blood pigment that carries oxygen, which is bound to glucose. The term HbA1c also refers to glycated hemoglobin. High levels of HbA1c (Normal range is less than 6%) indicate poorer control of diabetes than level in normal range.	Baseline and Week 24
Secondary	Percentage of Patients Experiencing at Least One Hypoglycaemia Accompanied by a Prespecified Glucose Value.	Hypoglycaemia accompanied by a prespecified glucose value is defined as any investigator reported hypoglycaemia (event or AE) with a reported blood glucose level of less than 54 milligram/deciLitre (3.0 millimole/Litre) or any investigator reported symptomatic hypoglycaemic AE with a reported blood glucose level of less or equal 70 milligram/deciLitre (3.9millimole/Litre) or any severe hypoglycaemic AE. Severe hypoglycaemia is an event that requires the assistance of another person to actively administer carbohydrates or glucagon because the patient is unable to take the substance on his or her own. The confidence intervals mentioned in measure of dispersion are exact 95% confidence interval by Clopper and Pearson. The percentage of patients with at least one hypoglycaemia accompanied by a glucose value less than 54mg/dL alone has also represented separately according American Diabetes Association definition of clinically significant hypoglycaemia.	24 weeks
Secondary	Percentage of Patients With HbA1c<8.0%	This is the percentage of patients with HbA1c on treatment <8.0% after 24 weeks of treatment. The confidence intervals mentioned in measure of dispersion are exact 95% CI by Clopper and Pearson.	24 weeks
Secondary	Percentage of Patients With HbA1c on Treatment <7.0%	This is the percentage of patients with HbA1c on treatment <7.0% after 24 weeks of treatment. The confidence intervals mentioned in measure of dispersion are exact 95% CI by Clopper and Pearson.	24 weeks
Secondary	Percentage of Patients With HbA1c Lowering by at Least 0.5%.	The percentage of patients who attained lowering of HbA1c by =0.5% from baseline after 24 weeks of treatment were analysed. The confidence intervals mentioned in measure of dispersion are exact 95% CI by Clopper and Pearson.	24 weeks
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG)	This outcome has measured difference between FPG values from baseline to 24 weeks post treatment. The term 'baseline' refers to the last observation prior to the administration of any randomised study medication	Baseline and Week 24