Clinical trial NCT00954447: Efficacy and Safety of Linagliptin in Combination With Insulin in Patients With Type 2 Diabetes
Official title: A Phase III Randomised, Double-blind, Placebo-controlled, Parallel Group Efficacy and Safety Study of Linagliptin (5 mg), Administered Orally Once Daily for at Least 52 Weeks in Type 2 Diabetic Patients in Combination With Basal Insulin Therapy
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: 2009-08-07
Enrollment: 1263
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of the current study is to investigate the efficacy, safety and tolerability of linagliptin (5 mg / once daily) compared to Placebo during long term treatment (52 weeks and longer) in combination with basal insulin in patients with type 2 diabetes mellitus with insufficient glycaemic control.


Eligibility criteria: Inclusion criteria:

1. Diabetes type 2, detectable C-peptide, HbA1c 7-10%
2. Pretreatment with basal insulin +/- Metformin or/and +/- Pioglitazone 3 Age \> 18 years, BMI \<= 45 kg/m2

Exclusion criteria:

1. Uncontrolled hyperglycemia during Run-in
2. Myocardial infarction, stroke or TIA within 3 months prior to informed consent
3. Liver impairment; gastric surgery; medical history of cancer in last 5 years
4. Other antidiabetic drugs, antiobesity drugs, systemic steroids, other investigational drug before randomisation
5. Unsufficient birth control, pregnancy and nursing

Primary outcomes:
measure: Change From Baseline in HbA1c After 24 Weeks
timeFrame: Baseline and 24 weeks
Secondary outcomes:
measure: Number of Patients With HbA1c < 7.0 Percent
timeFrame: 24 and 52 weeks
measure: Number of Patients Lowering HbA1c by at Least 0.5 Percent
timeFrame: 24 and 52 weeks
measure: Change From Baseline in HbA1c by Visit at Week 6
timeFrame: Baseline and 6 weeks
measure: Change From Baseline in HbA1c by Visit at Week 12
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in HbA1c by Visit at Week 18
timeFrame: Baseline and 18 weeks
measure: Change From Baseline in HbA1c by Visit at Week 32
timeFrame: Baseline and 32 weeks
measure: Change From Baseline in HbA1c by Visit at Week 40
timeFrame: Baseline and 40 weeks
measure: Change From Baseline in HbA1c by Visit at Week 52
timeFrame: Baseline and 52 weeks
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at 24 Weeks of Treatment
timeFrame: Baseline and 24 weeks
measure: Change From Baseline in Fasting Plasma Glucose (FPG) After 52 Weeks of Treatment
timeFrame: Baseline and 52 weeks
measure: Change From Baseline in FPG
timeFrame: Baseline, 6, 12, 18, 24, 32 and 40 weeks
measure: Change From Baseline in Mean Insulin Dose at 52 Weeks of Treatment
timeFrame: Baseline and 52 weeks
measure: Change From Baseline in Weighted Mean Daily Glucose After 24 and 52 Weeks of Treatment
timeFrame: Baseline, 24 and 52 weeks
measure: Change From Baseline in Incremental Post-prandial Glucose (iPPG) After 24 Weeks of Treatment
timeFrame: Baseline and 24 weeks: post-breakfast, post-lunch, post-dinner
Other outcomes:
measure: Number of Patients With HbA1c < 6.5 Percent
timeFrame: 24 and 52 weeks
Locations:
city: Escondido
country: United States
facility: 1218.36.01043 Boehringer Ingelheim Investigational Site
state: California
city: Escondido
country: United States
facility: 1218.36.01051 Boehringer Ingelheim Investigational Site
state: California
city: Fresno
country: United States
facility: 1218.36.01065 Boehringer Ingelheim Investigational Site
state: California
city: Greenbrae
country: United States
facility: 1218.36.01021 Boehringer Ingelheim Investigational Site
state: California
city: Los Angeles
country: United States
facility: 1218.36.01013 Boehringer Ingelheim Investigational Site
state: California
city: Los Angeles
country: United States
facility: 1218.36.01048 Boehringer Ingelheim Investigational Site
state: California
city: San Diego
country: United States
facility: 1218.36.01058 Boehringer Ingelheim Investigational Site
state: California
city: Santa Ana
country: United States
facility: 1218.36.01008 Boehringer Ingelheim Investigational Site
state: California
city: Waterbury
country: United States
facility: 1218.36.01056 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Clearwater
country: United States
facility: 1218.36.01054 Boehringer Ingelheim Investigational Site
state: Florida
city: Inverness
country: United States
facility: 1218.36.01035 Boehringer Ingelheim Investigational Site
state: Florida
city: Miami
country: United States
facility: 1218.36.01010 Boehringer Ingelheim Investigational Site
state: Florida
city: New Port Richey
country: United States
facility: 1218.36.01042 Boehringer Ingelheim Investigational Site
state: Florida
city: Pembroke Pines
country: United States
facility: 1218.36.01063 Boehringer Ingelheim Investigational Site
state: Florida
city: Ponte Vedra
country: United States
facility: 1218.36.01037 Boehringer Ingelheim Investigational Site
state: Florida
city: St. Cloud
country: United States
facility: 1218.36.01032 Boehringer Ingelheim Investigational Site
state: Florida
city: St. Petersburg
country: United States
facility: 1218.36.01049 Boehringer Ingelheim Investigational Site
state: Florida
city: Atlanta
country: United States
facility: 1218.36.01036 Boehringer Ingelheim Investigational Site
state: Georgia
city: Decatur
country: United States
facility: 1218.36.01047 Boehringer Ingelheim Investigational Site
state: Georgia
city: Roswell
country: United States
facility: 1218.36.01009 Boehringer Ingelheim Investigational Site
state: Georgia
city: Honolulu
country: United States
facility: 1218.36.01055 Boehringer Ingelheim Investigational Site
state: Hawaii
city: Chicago
country: United States
facility: 1218.36.01014 Boehringer Ingelheim Investigational Site
state: Illinois
city: Paducah
country: United States
facility: 1218.36.01011 Boehringer Ingelheim Investigational Site
state: Kentucky
city: Kansas City
country: United States
facility: 1218.36.01040 Boehringer Ingelheim Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: 1218.36.01029 Boehringer Ingelheim Investigational Site
state: Missouri
city: St. Peters
country: United States
facility: 1218.36.01034 Boehringer Ingelheim Investigational Site
state: Missouri
city: Omaha
country: United States
facility: 1218.36.01018 Boehringer Ingelheim Investigational Site
state: Nebraska
city: New Hartford
country: United States
facility: 1218.36.01053 Boehringer Ingelheim Investigational Site
state: New York
city: Burlington
country: United States
facility: 1218.36.01006 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Hickory
country: United States
facility: 1218.36.01025 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Statesville
country: United States
facility: 1218.36.01005 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: 1218.36.01015 Boehringer Ingelheim Investigational Site
state: Ohio
city: Tulsa
country: United States
facility: 1218.36.01039 Boehringer Ingelheim Investigational Site
state: Oklahoma
city: Altoona
country: United States
facility: 1218.36.01019 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Norristown
country: United States
facility: 1218.36.01012 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Greer
country: United States
facility: 1218.36.01004 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Simpsonville
country: United States
facility: 1218.36.01020 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Kingsport
country: United States
facility: 1218.36.01003 Boehringer Ingelheim Investigational Site
state: Tennessee
city: Dallas
country: United States
facility: 1218.36.01038 Boehringer Ingelheim Investigational Site
state: Texas
city: Houston
country: United States
facility: 1218.36.01016 Boehringer Ingelheim Investigational Site
state: Texas
city: Salt Lake city
country: United States
facility: 1218.36.01026 Boehringer Ingelheim Investigational Site
state: Utah
city: Bennington
country: United States
facility: 1218.36.01041 Boehringer Ingelheim Investigational Site
state: Vermont
city: Richmond
country: United States
facility: 1218.36.01064 Boehringer Ingelheim Investigational Site
state: Virginia
city: Lakewood
country: United States
facility: 1218.36.01024 Boehringer Ingelheim Investigational Site
state: Washington
city: Renton
country: United States
facility: 1218.36.01007 Boehringer Ingelheim Investigational Site
state: Washington
city: Spokane
country: United States
facility: 1218.36.01027 Boehringer Ingelheim Investigational Site
state: Washington
city: Tacoma
country: United States
facility: 1218.36.01062 Boehringer Ingelheim Investigational Site
state: Washington
city: Capital Federal
country: Argentina
facility: 1218.36.54001 Boehringer Ingelheim Investigational Site
city: Capital Federal
country: Argentina
facility: 1218.36.54002 Boehringer Ingelheim Investigational Site
city: Capital Federal
country: Argentina
facility: 1218.36.54003 Boehringer Ingelheim Investigational Site
city: Capital Federal
country: Argentina
facility: 1218.36.54005 Boehringer Ingelheim Investigational Site
city: Córdoba
country: Argentina
facility: 1218.36.54004 Boehringer Ingelheim Investigational Site
city: Edegem
country: Belgium
facility: 1218.36.32002 Boehringer Ingelheim Investigational Site
city: Edegem
country: Belgium
facility: 1218.36.320099 Boehringer Ingelheim Investigational Site
city: Sint-Gillis-Waas
country: Belgium
facility: 1218.36.32006 Boehringer Ingelheim Investigational Site
city: Belém
country: Brazil
facility: 1218.36.55003 Boehringer Ingelheim Investigational Site
city: Porto Alegre
country: Brazil
facility: 1218.36.55004 Boehringer Ingelheim Investigational Site
city: São Paulo
country: Brazil
facility: 1218.36.55001 Boehringer Ingelheim Investigational Site
city: São Paulo
country: Brazil
facility: 1218.36.55002 Boehringer Ingelheim Investigational Site
city: Calgary
country: Canada
facility: 1218.36.02010 Boehringer Ingelheim Investigational Site
state: Alberta
city: Vancouver
country: Canada
facility: 1218.36.02004 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Victoria
country: Canada
facility: 1218.36.02011 Boehringer Ingelheim Investigational Site
state: British Columbia
city: St. John's
country: Canada
facility: 1218.36.02006 Boehringer Ingelheim Investigational Site
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: 1218.36.02002 Boehringer Ingelheim Investigational Site
state: Nova Scotia
city: Hamilton
country: Canada
facility: 1218.36.02009 Boehringer Ingelheim Investigational Site
state: Ontario
city: Kingston
country: Canada
facility: 1218.36.02005 Boehringer Ingelheim Investigational Site
state: Ontario
city: Sarnia
country: Canada
facility: 1218.36.02008 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1218.36.02007 Boehringer Ingelheim Investigational Site
state: Ontario
city: Laval
country: Canada
facility: 1218.36.02001 Boehringer Ingelheim Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: 1218.36.02003 Boehringer Ingelheim Investigational Site
state: Quebec
city: Breclav
country: Czech Republic
facility: 1218.36.42006 Boehringer Ingelheim Investigational Site
city: Brno
country: Czech Republic
facility: 1218.36.42004 Boehringer Ingelheim Investigational Site
city: Hodonin
country: Czech Republic
facility: 1218.36.42005 Boehringer Ingelheim Investigational Site
city: Mlada Boleslav
country: Czech Republic
facility: 1218.36.42002 Boehringer Ingelheim Investigational Site
city: Neratovice
country: Czech Republic
facility: 1218.36.42001 Boehringer Ingelheim Investigational Site
city: Zlin
country: Czech Republic
facility: 1218.36.42007 Boehringer Ingelheim Investigational Site
city: Joensuu
country: Finland
facility: 1218.36.35807 Boehringer Ingelheim Investigational Site
city: Kuopio
country: Finland
facility: 1218.36.35802 Boehringer Ingelheim Investigational Site
city: Oulu
country: Finland
facility: 1218.36.35803 Boehringer Ingelheim Investigational Site
city: Tampere
country: Finland
facility: 1218.36.35805 Boehringer Ingelheim Investigational Site
city: Turku
country: Finland
facility: 1218.36.35804 Boehringer Ingelheim Investigational Site
city: Vantaa
country: Finland
facility: 1218.36.35806 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1218.36.49001 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1218.36.49002 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1218.36.49010 Boehringer Ingelheim Investigational Site
city: Bosenheim
country: Germany
facility: 1218.36.49009 Boehringer Ingelheim Investigational Site
city: Dortmund
country: Germany
facility: 1218.36.49004 Boehringer Ingelheim Investigational Site
city: Dresden
country: Germany
facility: 1218.36.49006 Boehringer Ingelheim Investigational Site
city: Köln
country: Germany
facility: 1218.36.49017 Boehringer Ingelheim Investigational Site
city: Magdeburg
country: Germany
facility: 1218.36.49012 Boehringer Ingelheim Investigational Site
city: Mainz
country: Germany
facility: 1218.36.49005 Boehringer Ingelheim Investigational Site
city: Neuwied
country: Germany
facility: 1218.36.49018 Boehringer Ingelheim Investigational Site
city: Pirna
country: Germany
facility: 1218.36.49008 Boehringer Ingelheim Investigational Site
city: Sulzbach-Rosenberg
country: Germany
facility: 1218.36.49019 Boehringer Ingelheim Investigational Site
city: Unterschneidheim
country: Germany
facility: 1218.36.49003 Boehringer Ingelheim Investigational Site
city: Wangen
country: Germany
facility: 1218.36.49011 Boehringer Ingelheim Investigational Site
city: Wangen
country: Germany
facility: 1218.36.49014 Boehringer Ingelheim Investigational Site
city: Westerkappeln
country: Germany
facility: 1218.36.49015 Boehringer Ingelheim Investigational Site
city: Athens
country: Greece
facility: 1218.36.30003 Boehringer Ingelheim Investigational Site
city: Athens
country: Greece
facility: 1218.36.30007 Boehringer Ingelheim Investigational Site
city: Athens
country: Greece
facility: 1218.36.30010 Boehringer Ingelheim Investigational Site
city: Larissa
country: Greece
facility: 1218.36.30011 Boehringer Ingelheim Investigational Site
city: Nikaia
country: Greece
facility: 1218.36.30002 Boehringer Ingelheim Investigational Site
city: Thessaloniki
country: Greece
facility: 1218.36.30005 Boehringer Ingelheim Investigational Site
city: Ferrara
country: Italy
facility: 1218.36.39002 Boehringer Ingelheim Investigational Site
city: Ferrara
country: Italy
facility: 1218.36.39003 Boehringer Ingelheim Investigational Site
city: Genova
country: Italy
facility: 1218.36.39004 Boehringer Ingelheim Investigational Site
city: Milano
country: Italy
facility: 1218.36.39005 Boehringer Ingelheim Investigational Site
city: Pordenone
country: Italy
facility: 1218.36.39001 Boehringer Ingelheim Investigational Site
city: Siena
country: Italy
facility: 1218.36.39007 Boehringer Ingelheim Investigational Site
city: Siracusa
country: Italy
facility: 1218.36.39006 Boehringer Ingelheim Investigational Site
city: Daegu
country: Korea, Republic of
facility: 1218.36.82004 Boehringer Ingelheim Investigational Site
city: Daegu
country: Korea, Republic of
facility: 1218.36.82009 Boehringer Ingelheim Investigational Site
city: Incheon
country: Korea, Republic of
facility: 1218.36.82008 Boehringer Ingelheim Investigational Site
city: Jeonju
country: Korea, Republic of
facility: 1218.36.82007 Boehringer Ingelheim Investigational Site
city: Pusan
country: Korea, Republic of
facility: 1218.36.82001 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1218.36.82002 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1218.36.82003 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1218.36.82005 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1218.36.82006 Boehringer Ingelheim Investigational Site
city: Suwon
country: Korea, Republic of
facility: 1218.36.82010 Boehringer Ingelheim Investigational Site
city: Pachuca
country: Mexico
facility: 1218.36.52002 Boehringer Ingelheim Investigational Site
city: San Luis Potosi
country: Mexico
facility: 1218.36.52004 Boehringer Ingelheim Investigational Site
city: Tijuana
country: Mexico
facility: 1218.36.52005 Boehringer Ingelheim Investigational Site
city: 's Hertogenbosch
country: Netherlands
facility: 1218.36.31008 Boehringer Ingelheim Investigational Site
city: Almere
country: Netherlands
facility: 1218.36.31001 Boehringer Ingelheim Investigational Site
city: Beek
country: Netherlands
facility: 1218.36.31006 Boehringer Ingelheim Investigational Site
city: Ewijk
country: Netherlands
facility: 1218.36.31002 Boehringer Ingelheim Investigational Site
city: Oude Pekela
country: Netherlands
facility: 1218.36.31004 Boehringer Ingelheim Investigational Site
city: Roelofarendsveen
country: Netherlands
facility: 1218.36.31007 Boehringer Ingelheim Investigational Site
city: Wildervank
country: Netherlands
facility: 1218.36.31005 Boehringer Ingelheim Investigational Site
city: Bergen
country: Norway
facility: 1218.36.47002 Boehringer Ingelheim Investigational Site
city: Elverum
country: Norway
facility: 1218.36.47006 Boehringer Ingelheim Investigational Site
city: Hamar
country: Norway
facility: 1218.36.47005 Boehringer Ingelheim Investigational Site
city: Oslo
country: Norway
facility: 1218.36.47004 Boehringer Ingelheim Investigational Site
city: Stavanger
country: Norway
facility: 1218.36.47001 Boehringer Ingelheim Investigational Site
city: Lima
country: Peru
facility: 1218.36.51003 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1218.36.70002 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1218.36.70003 Boehringer Ingelheim Investigational Site
city: Samara
country: Russian Federation
facility: 1218.36.70001 Boehringer Ingelheim Investigational Site
city: Smolensk
country: Russian Federation
facility: 1218.36.70007 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 1218.36.70005 Boehringer Ingelheim Investigational Site
city: Yaroslavl
country: Russian Federation
facility: 1218.36.70006 Boehringer Ingelheim Investigational Site
city: Banska Bystrica
country: Slovakia
facility: 1218.36.42103 Boehringer Ingelheim Investigational Site
city: Bratislava
country: Slovakia
facility: 1218.36.42101 Boehringer Ingelheim Investigational Site
city: Bratislava
country: Slovakia
facility: 1218.36.42102 Boehringer Ingelheim Investigational Site
city: Bratislava
country: Slovakia
facility: 1218.36.42104 Boehringer Ingelheim Investigational Site
city: Presov
country: Slovakia
facility: 1218.36.42105 Boehringer Ingelheim Investigational Site
city: Trebisov
country: Slovakia
facility: 1218.36.42106 Boehringer Ingelheim Investigational Site
city: Badia del Vallés (Barcelona)
country: Spain
facility: 1218.36.34002 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1218.36.34005 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1218.36.34010 Boehringer Ingelheim Investigational Site
city: Bercelona
country: Spain
facility: 1218.36.34001 Boehringer Ingelheim Investigational Site
city: Borges del Camp (Tarragona)
country: Spain
facility: 1218.36.34007 Boehringer Ingelheim Investigational Site
city: Centelles (Barcelona)
country: Spain
facility: 1218.36.34003 Boehringer Ingelheim Investigational Site
city: L'Hospitalet de Llobregat (Barcelona)
country: Spain
facility: 1218.36.34004 Boehringer Ingelheim Investigational Site
city: Sevilla
country: Spain
facility: 1218.36.34011 Boehringer Ingelheim Investigational Site
city: Tàrrega (Lleida)
country: Spain
facility: 1218.36.34009 Boehringer Ingelheim Investigational Site
city: Vic (Barcelona)
country: Spain
facility: 1218.36.34006 Boehringer Ingelheim Investigational Site
city: Changhua
country: Taiwan
facility: 1218.36.88610 Boehringer Ingelheim Investigational Site
city: Kaohsiung
country: Taiwan
facility: 1218.36.88607 Boehringer Ingelheim Investigational Site
city: Taichung
country: Taiwan
facility: 1218.36.88601 Boehringer Ingelheim Investigational Site
city: Taichung
country: Taiwan
facility: 1218.36.88603 Boehringer Ingelheim Investigational Site
city: Tainan
country: Taiwan
facility: 1218.36.88606 Boehringer Ingelheim Investigational Site
city: Taipei City
country: Taiwan
facility: 1218.36.88609 Boehringer Ingelheim Investigational Site
city: Taipei
country: Taiwan
facility: 1218.36.88602 Boehringer Ingelheim Investigational Site
city: Taipei
country: Taiwan
facility: 1218.36.88604 Boehringer Ingelheim Investigational Site
city: Taipei
country: Taiwan
facility: 1218.36.88605 Boehringer Ingelheim Investigational Site
city: Taipei
country: Taiwan
facility: 1218.36.88608 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Sheu WH, Park SW, Gong Y, Pinnetti S, Bhattacharya S, Patel S, Seck T, Woerle HJ. Linagliptin improves glycemic control after 1 year as add-on therapy to basal insulin in Asian patients with type 2 diabetes mellitus. Curr Med Res Opin. 2015 Mar;31(3):503-12. doi: 10.1185/03007995.2015.1010638. Epub 2015 Feb 13.
citation: Yki-Jarvinen H, Rosenstock J, Duran-Garcia S, Pinnetti S, Bhattacharya S, Thiemann S, Patel S, Woerle HJ. Effects of adding linagliptin to basal insulin regimen for inadequately controlled type 2 diabetes: a >/=52-week randomized, double-blind study. Diabetes Care. 2013 Dec;36(12):3875-81. doi: 10.2337/dc12-2718. Epub 2013 Sep 23.