Clinical trial NCT00982644: Comparison of NN1250 Versus Insulin Glargine in Subjects With Type 2 Diabetes
Official title: NN1250-3579: A 52-week Randomised, Controlled, Open Label, Multicentre, Multinational Treat-to-target Trial Comparing the Efficacy and Safety of SIBA and Insulin Glargine, Both Injected Once Daily in Combination With Oral Anti-diabetic Drugs (OAD), in Subjects With Type 2 Diabetes Mellitus Currently Treated With OAD(s) and Qualifying for More Intensified Treatment / NN1250-3643: An Extension Trial to NN1250-3579 Comparing Safety and Efficacy of NN1250 Plus OAD(s) With Insulin Glargine Plus OAD(s) in Type 2 Diabetes (BEGIN™: Once Long)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2009-09-23
Enrollment: 1030
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: This trial is conducted in Europe and the United States of America (USA). The aim of this trial is to compare NN1250 (insulin degludec (IDeg)) with insulin glargine (IGlar) in subjects with type 2 diabetes never treated with insulin followed by the extension trial investigating the long-term safety and tolerability in terms of comparing NN1250 with insulin glargine in subjects with type 2 diabetes.

All oral anti-diabetic drug (OAD) treatment will be discontinued when trial participant enters the main trial (NN1250-3579) with the exception of metformin and dipeptidyl peptidase-IV (DPP-IV) inhibitor treatment (only in countries where DPP-IV inhibitor treatment is approved for combination treatment together with insulin, otherwise DPP-IV inhibitor treatment is also discontinued). Subjects who consent to participate in the extension trial will continue the treatment (NN1250 or insulin glargine + oral antidiabetic drugs (OADs)) to which they were randomly allocated in the 52 week main trial.

The main period is registered internally at Novo Nordisk as NN1250-3579 while the extension period is registered as NN1250-3643.


Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes mellitus
* Treatment with oral antidiabetic drugs (OADs) for at least three months before trial start at an unchanged dose
* HbA1c: 7.0-10.0%
* Body Mass Index (BMI) no higher than 40.0 kg/m\^2
* For the extension trial only: Completion of the 52 week treatment period in trial NN1250-3579 (NCT00982644)

Exclusion Criteria:

* Treatment with exenatide or liraglutide within the last 3 months before trial start
* Cardiovascular disease within the last 6 months
* Uncontrolled treated/untreated severe hypertension
* Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures
* Cancer and medical history of cancer

Primary outcomes:
measure: Main Trial (Primary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 52 Weeks of Treatment
timeFrame: Week 0, Week 52
measure: Extension Trial (Primary Endpoint): Rate of Confirmed Hypoglycaemic Episodes
timeFrame: Week 0 to Week 104 + 7 days follow up
measure: Extension Trial (Primary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes
timeFrame: Week 0 to Week 104 + 7 days follow up
measure: Extension Trial (Primary Endpoint): Rate of Treatment Emergent Adverse Events (AEs)
timeFrame: Week 0 to Week 104 + 7 days of follow up
Secondary outcomes:
measure: Main Trial (Secondary Endpoint): Rate of Confirmed Hypoglycaemic Episodes
timeFrame: Week 0 to Week 52 + 7 days follow up
measure: Extension Trial (Secondary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 104 Weeks of Treatment
timeFrame: Week 0, Week 104
measure: Main Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 52
timeFrame: Week 52
measure: Extension Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 104
timeFrame: Week 104
measure: Main Trial (Secondary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes
timeFrame: Week 0 to Week 52 + 7 days follow up
Other outcomes:
Locations:
city: Bay Minette
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Birmingham
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Huntsville
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Goodyear
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Anaheim
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Concord
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: La Jolla
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Lancaster
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Long Beach
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Los Angeles
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Mission Hills
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: National City
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: North Hollywood
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Northridge
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Palm Springs
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: San Mateo
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Santa Monica
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Spring Valley
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Tarzana
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Tustin
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Norwalk
country: United States
facility: Novo Nordisk Investigational Site
state: Connecticut
city: Boynton Beach
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Melbourne
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Miami
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Miami
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: New Port Richey
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Orange Park
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Orlando
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Palm Harbor
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: West Palm Beach
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Decatur
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Fort Valley
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Idaho Falls
country: United States
facility: Novo Nordisk Investigational Site
state: Idaho
city: Chicago
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Evansville
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Indianapolis
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Lexington
country: United States
facility: Novo Nordisk Investigational Site
state: Kentucky
city: Paducah
country: United States
facility: Novo Nordisk Investigational Site
state: Kentucky
city: Metairie
country: United States
facility: Novo Nordisk Investigational Site
state: Louisiana
city: Slidell
country: United States
facility: Novo Nordisk Investigational Site
state: Louisiana
city: Greenbelt
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: North East
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Reisterstown
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Rockville
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Brockton
country: United States
facility: Novo Nordisk Investigational Site
state: Massachusetts
city: North Dartmouth
country: United States
facility: Novo Nordisk Investigational Site
state: Massachusetts
city: St. Louis
country: United States
facility: Novo Nordisk Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: Novo Nordisk Investigational Site
state: Missouri
city: Henderson
country: United States
facility: Novo Nordisk Investigational Site
state: Nevada
city: Las Vegas
country: United States
facility: Novo Nordisk Investigational Site
state: Nevada
city: Toms River
country: United States
facility: Novo Nordisk Investigational Site
state: New Jersey
city: Northport
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Staten Island
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Asheboro
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Charlotte
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Dayton
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Toledo
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: Novo Nordisk Investigational Site
state: Oklahoma
city: Kingston
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Langhorne
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Melrose Park
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: West Reading
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: East Providence
country: United States
facility: Novo Nordisk Investigational Site
state: Rhode Island
city: Columbia
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Greer
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Newberry
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Chattanooga
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Harriman
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Humboldt
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Arlington
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Corpus Christi
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: El Paso
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Hurst
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Irving
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Lubbock
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Sugar Land
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Richmond
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Spokane
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Milwaukee
country: United States
facility: Novo Nordisk Investigational Site
state: Wisconsin
city: Bregenz
country: Austria
facility: Novo Nordisk Investigational Site
city: Feldkirch
country: Austria
facility: Novo Nordisk Investigational Site
city: Wien
country: Austria
facility: Novo Nordisk Investigational Site
city: Wien
country: Austria
facility: Novo Nordisk Investigational Site
city: Wien
country: Austria
facility: Novo Nordisk Investigational Site
city: Wien
country: Austria
facility: Novo Nordisk Investigational Site
city: Wolfsberg
country: Austria
facility: Novo Nordisk Investigational Site
city: Brussels
country: Belgium
facility: Novo Nordisk Investigational Site
city: Brussels
country: Belgium
facility: Novo Nordisk Investigational Site
city: Gent
country: Belgium
facility: Novo Nordisk Investigational Site
city: Leuven
country: Belgium
facility: Novo Nordisk Investigational Site
city: Liège
country: Belgium
facility: Novo Nordisk Investigational Site
city: Edmonton
country: Canada
facility: Novo Nordisk Investigational Site
state: Alberta
city: Coquitlam
country: Canada
facility: Novo Nordisk Investigational Site
state: British Columbia
city: Winnipeg
country: Canada
facility: Novo Nordisk Investigational Site
state: Manitoba
city: Mount Pearl
country: Canada
facility: Novo Nordisk Investigational Site
state: Newfoundland and Labrador
city: St. John's
country: Canada
facility: Novo Nordisk Investigational Site
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Novo Nordisk Investigational Site
state: Nova Scotia
city: London
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Mississauga
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Scarborough
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: St-Marc-des-Carrières
country: Canada
facility: Novo Nordisk Investigational Site
state: Quebec
city: St. Romuald
country: Canada
facility: Novo Nordisk Investigational Site
state: Quebec
city: Quebec
country: Canada
facility: Novo Nordisk Investigational Site
city: Brno
country: Czech Republic
facility: Novo Nordisk Investigational Site
city: Hradec Kralove
country: Czech Republic
facility: Novo Nordisk Investigational Site
city: Plzen
country: Czech Republic
facility: Novo Nordisk Investigational Site
city: Prague 4
country: Czech Republic
facility: Novo Nordisk Investigational Site
city: Praha 5
country: Czech Republic
facility: Novo Nordisk Investigational Site
city: Esbjerg
country: Denmark
facility: Novo Nordisk Investigational Site
city: Hillerød
country: Denmark
facility: Novo Nordisk Investigational Site
city: Holbæk
country: Denmark
facility: Novo Nordisk Investigational Site
city: København S
country: Denmark
facility: Novo Nordisk Investigational Site
city: Odense
country: Denmark
facility: Novo Nordisk Investigational Site
city: Silkeborg
country: Denmark
facility: Novo Nordisk Investigational Site
city: Helsinki
country: Finland
facility: Novo Nordisk Investigational Site
city: Joensuu
country: Finland
facility: Novo Nordisk Investigational Site
city: Kerava
country: Finland
facility: Novo Nordisk Investigational Site
city: Lohja
country: Finland
facility: Novo Nordisk Investigational Site
city: Oulu
country: Finland
facility: Novo Nordisk Investigational Site
city: Tampere
country: Finland
facility: Novo Nordisk Investigational Site
city: Belgrade
country: Former Serbia and Montenegro
facility: Novo Nordisk Investigational Site
city: Kragujevac
country: Former Serbia and Montenegro
facility: Novo Nordisk Investigational Site
city: Nis
country: Former Serbia and Montenegro
facility: Novo Nordisk Investigational Site
city: Novi Sad
country: Former Serbia and Montenegro
facility: Novo Nordisk Investigational Site
city: Le Grau-du-Roi
country: France
facility: Novo Nordisk Investigational Site
city: Montigny-les-Metz
country: France
facility: Novo Nordisk Investigational Site
city: Nanterre
country: France
facility: Novo Nordisk Investigational Site
city: Nantes
country: France
facility: Novo Nordisk Investigational Site
city: Nimes
country: France
facility: Novo Nordisk Investigational Site
city: Saint-denis de La Reunion
country: France
facility: Novo Nordisk Investigational Site
city: Venissieux
country: France
facility: Novo Nordisk Investigational Site
city: Bad Harzburg
country: Germany
facility: Novo Nordisk Investigational Site
city: Berlin
country: Germany
facility: Novo Nordisk Investigational Site
city: Berlin
country: Germany
facility: Novo Nordisk Investigational Site
city: Dormagen
country: Germany
facility: Novo Nordisk Investigational Site
city: Dresden
country: Germany
facility: Novo Nordisk Investigational Site
city: Essen
country: Germany
facility: Novo Nordisk Investigational Site
city: Friedrichsthal
country: Germany
facility: Novo Nordisk Investigational Site
city: Hamburg
country: Germany
facility: Novo Nordisk Investigational Site
city: Hamburg
country: Germany
facility: Novo Nordisk Investigational Site
city: Hamburg
country: Germany
facility: Novo Nordisk Investigational Site
city: Hohenmölsen
country: Germany
facility: Novo Nordisk Investigational Site
city: Neuwied
country: Germany
facility: Novo Nordisk Investigational Site
city: Pohlheim
country: Germany
facility: Novo Nordisk Investigational Site
city: Rehburg-Loccum
country: Germany
facility: Novo Nordisk Investigational Site
city: Rehlingen-Siersburg
country: Germany
facility: Novo Nordisk Investigational Site
city: Riesa
country: Germany
facility: Novo Nordisk Investigational Site
city: Speyer
country: Germany
facility: Novo Nordisk Investigational Site
city: St. Ingbert
country: Germany
facility: Novo Nordisk Investigational Site
city: Bekkestua
country: Norway
facility: Novo Nordisk Investigational Site
city: Elverum
country: Norway
facility: Novo Nordisk Investigational Site
city: Hamar
country: Norway
facility: Novo Nordisk Investigational Site
city: Kongsvinger
country: Norway
facility: Novo Nordisk Investigational Site
city: Oslo
country: Norway
facility: Novo Nordisk Investigational Site
city: Stavanger
country: Norway
facility: Novo Nordisk Investigational Site
city: Trondheim
country: Norway
facility: Novo Nordisk Investigational Site
city: Ålesund
country: Norway
facility: Novo Nordisk Investigational Site
city: Bayamon
country: Puerto Rico
facility: Novo Nordisk Investigational Site
city: Belgrade
country: Serbia
facility: Novo Nordisk Investigational Site
city: Kragujevac
country: Serbia
facility: Novo Nordisk Investigational Site
city: Nis
country: Serbia
facility: Novo Nordisk Investigational Site
city: Novi Sad
country: Serbia
facility: Novo Nordisk Investigational Site
city: Koper
country: Slovenia
facility: Novo Nordisk Investigational Site
city: Ljubljana
country: Slovenia
facility: Novo Nordisk Investigational Site
city: Novo mesto
country: Slovenia
facility: Novo Nordisk Investigational Site
city: Almería
country: Spain
facility: Novo Nordisk Investigational Site
city: Alzira
country: Spain
facility: Novo Nordisk Investigational Site
city: Antequera
country: Spain
facility: Novo Nordisk Investigational Site
city: El Ferrol
country: Spain
facility: Novo Nordisk Investigational Site
city: Gijón
country: Spain
facility: Novo Nordisk Investigational Site
city: Inca
country: Spain
facility: Novo Nordisk Investigational Site
city: Palma de Mallorca
country: Spain
facility: Novo Nordisk Investigational Site
city: Puerto del Rosario
country: Spain
facility: Novo Nordisk Investigational Site
city: Sevilla
country: Spain
facility: Novo Nordisk Investigational Site
city: Sevilla
country: Spain
facility: Novo Nordisk Investigational Site
city: Valencia
country: Spain
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR, 1452)
role: STUDY_DIRECTOR
References:
citation: Ratner RE, Gough SC, Mathieu C, Del Prato S, Bode B, Mersebach H, Endahl L, Zinman B. Hypoglycaemia risk with insulin degludec compared with insulin glargine in type 2 and type 1 diabetes: a pre-planned meta-analysis of phase 3 trials. Diabetes Obes Metab. 2013 Feb;15(2):175-84. doi: 10.1111/dom.12032. Epub 2012 Dec 3.
citation: Sorli C, Warren M, Oyer D, Mersebach H, Johansen T, Gough SC. Elderly patients with diabetes experience a lower rate of nocturnal hypoglycaemia with insulin degludec than with insulin glargine: a meta-analysis of phase IIIa trials. Drugs Aging. 2013 Dec;30(12):1009-18. doi: 10.1007/s40266-013-0128-2.
citation: Einhorn D, Handelsman Y, Bode BW, Endahl LA, Mersebach H, King AB. PATIENTS ACHIEVING GOOD GLYCEMIC CONTROL (HBA1c <7%) EXPERIENCE A LOWER RATE OF HYPOGLYCEMIA WITH INSULIN DEGLUDEC THAN WITH INSULIN GLARGINE: A META-ANALYSIS OF PHASE 3A TRIALS. Endocr Pract. 2015 Aug;21(8):917-26. doi: 10.4158/EP14523.OR. Epub 2015 Jun 29.
citation: Russell-Jones D, Gall MA, Niemeyer M, Diamant M, Del Prato S. Insulin degludec results in lower rates of nocturnal hypoglycaemia and fasting plasma glucose vs. insulin glargine: A meta-analysis of seven clinical trials. Nutr Metab Cardiovasc Dis. 2015 Oct;25(10):898-905. doi: 10.1016/j.numecd.2015.06.005. Epub 2015 Jun 18.
citation: Vora J, Seufert J, Solberg H, Kinduryte O, Johansen T, Hollander P. Insulin degludec does not increase antibody formation versus insulin glargine: an evaluation of phase IIIa trials. Diabetes Obes Metab. 2016 Jul;18(7):716-20. doi: 10.1111/dom.12621. Epub 2016 Feb 8.
citation: Rodbard HW, Cariou B, Zinman B, Handelsman Y, Philis-Tsimikas A, Skjoth TV, Rana A, Mathieu C; BEGIN Once Long trial investigators. Comparison of insulin degludec with insulin glargine in insulin-naive subjects with Type 2 diabetes: a 2-year randomized, treat-to-target trial. Diabet Med. 2013 Nov;30(11):1298-304. doi: 10.1111/dme.12303. Epub 2013 Sep 30.