Clinical trial NCT00972283: Comparison of NN1250 With Insulin Glargine Plus Insulin Aspart With/Without Metformin and With/Without Pioglitazone in Type 2 Diabetes
Official title: NN1250-3582: A 52-week Randomised, Controlled, Open Label, Multicentre, Multinational Treat-to-target Trial Comparing Efficacy and Safety of SIBA and Insulin Glargine Both Administered Once Daily in a Basal-bolus Regimen With Insulin Aspart as Mealtime Insulin ± Treatment With Metformin, ± Pioglitazone in Subjects With Type 2 Diabetes Currently Treated With Insulin Qualifying for Intensified Treatment/NN1250-3667: An Extension Trial to NN1250-3582 Comparing Safety and Efficacy of NN1250 and Insulin Glargine, Both With Insulin Aspart as Meal-time Insulin ± OADs in Type 2 Diabetes (BEGIN™: BB)
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: 2009-09-04
Enrollment: 1006
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 Africa, Asia, Europe, and the United States of America (USA).

The aim of this clinical trial is to compare NN1250 (insulin degludec (IDeg)) with insulin glargine (IGlar) plus insulin aspart (IAsp) with/without metformin and with/without pioglitazone in subjects with type 2 diabetes (main period) followed by investigating the long-term safety in terms of comparing NN1250 with insulin glargine plus insulin aspart with or without metformin and with or without pioglitazone in subjects with type 2 diabetes.

All oral anti-diabetic drug (OAD) treatment will be discontinued, if applicable, when trial participant enters the trial (NN1250-3582) with the exception of metformin and pioglitazone.

Subjects who consent to participate in the extension trial (NN1250-3667) will continue to receive the treatment to which they were randomly allocated in the 52 week trial NN1250-3582.

The main period is registered internally at Novo Nordisk as NN1250-3582 while the extension period is registered as NN1250-3667.


Eligibility criteria: Inclusion Criteria:

* For MAIN period (NN1250-3582):
* Type 2 diabetes mellitus for at least 6 months
* Ongoing daily treatment with insulin (premix, self-mix, basal only, basal bolus) for at least 3 months with/without oral anti-diabetics drug (OAD) prior to trial start
* HbA1c 7.0-10.0 % (both inclusive)
* Body Mass Index (BMI) below or equal to 40.0 kg/m\^2
* For EXTENSION period (NN1250-3667):
* Completion of the 52 week treatment period in NN1250-3582

Exclusion Criteria:

* For MAIN period (NN1250-3582):
* Treatment with other insulin regimens than premix, self-mix, basal only, basal bolus within 3 months
* 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 78 + 7 days follow up
measure: Extension Trial (Primary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes
timeFrame: Week 0 to Week 78 + 7 days follow up
measure: Rate of Treatment Emergent Adverse Events (AEs)
timeFrame: Week 0 to Week 78 + 7 days follow up
Secondary outcomes:
measure: Extension Trial (Secondary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 78 Weeks of Treatment
timeFrame: Week 0, Week 78
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 78
timeFrame: Week 78
measure: Main Trial (Secondary Endpoint): Rate of Confirmed Hypoglycaemic Episodes
timeFrame: Week 0 to Week 52 + 7 days follow up
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: Alexander City
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Birmingham
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Goodyear
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Peoria
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Anaheim
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Huntington Beach
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Los Gatos
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Salinas
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: Tustin
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Walnut Creek
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Milford
country: United States
facility: Novo Nordisk Investigational Site
state: Connecticut
city: Norwalk
country: United States
facility: Novo Nordisk Investigational Site
state: Connecticut
city: Waterbury
country: United States
facility: Novo Nordisk Investigational Site
state: Connecticut
city: Washington
country: United States
facility: Novo Nordisk Investigational Site
state: District of Columbia
city: Gainesville
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Lake Mary
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Orlando
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Plantation
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: Atlanta
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Fort Valley
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Honolulu
country: United States
facility: Novo Nordisk Investigational Site
state: Hawaii
city: Nampa
country: United States
facility: Novo Nordisk Investigational Site
state: Idaho
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: New Albany
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Metairie
country: United States
facility: Novo Nordisk Investigational Site
state: Louisiana
city: Metairie
country: United States
facility: Novo Nordisk Investigational Site
state: Louisiana
city: Hyattsville
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: North East
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Rockville
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Eagan
country: United States
facility: Novo Nordisk Investigational Site
state: Minnesota
city: Jefferson City
country: United States
facility: Novo Nordisk Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: Novo Nordisk Investigational Site
state: Missouri
city: Lincoln
country: United States
facility: Novo Nordisk Investigational Site
state: Nebraska
city: Omaha
country: United States
facility: Novo Nordisk Investigational Site
state: Nebraska
city: Las Vegas
country: United States
facility: Novo Nordisk Investigational Site
state: Nevada
city: Lawrenceville
country: United States
facility: Novo Nordisk Investigational Site
state: New Jersey
city: Toms River
country: United States
facility: Novo Nordisk Investigational Site
state: New Jersey
city: Charlotte
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Greenville
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Columbus
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Toledo
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Danville
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Kingston
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Melrose Park
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Wilkes Barre
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Charleston
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: Kingsport
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
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: Fort Worth
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Round Rock
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Salt Lake City
country: United States
facility: Novo Nordisk Investigational Site
state: Utah
city: Richmond
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Olympia
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Renton
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Dimitrovgrad
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Ruse
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Sofia
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Sofia
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Sofia
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Stara Zagora
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Varna
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Dresden
country: Germany
facility: Novo Nordisk Investigational Site
city: Dresden
country: Germany
facility: Novo Nordisk Investigational Site
city: Frankfurt
country: Germany
facility: Novo Nordisk Investigational Site
city: Hamburg
country: Germany
facility: Novo Nordisk Investigational Site
city: Ludwigshafen
country: Germany
facility: Novo Nordisk Investigational Site
city: Münster
country: Germany
facility: Novo Nordisk Investigational Site
city: Völklingen
country: Germany
facility: Novo Nordisk Investigational Site
city: Wangen
country: Germany
facility: Novo Nordisk Investigational Site
city: Warburg
country: Germany
facility: Novo Nordisk Investigational Site
city: Shatin, New Territories
country: Hong Kong
facility: Novo Nordisk Investigational Site
city: Dublin
country: Ireland
facility: Novo Nordisk Investigational Site
city: Dublin
country: Ireland
facility: Novo Nordisk Investigational Site
city: Dublin
country: Ireland
facility: Novo Nordisk Investigational Site
city: Dublin
country: Ireland
facility: Novo Nordisk Investigational Site
city: Bari
country: Italy
facility: Novo Nordisk Investigational Site
city: Bergamo
country: Italy
facility: Novo Nordisk Investigational Site
city: Catania
country: Italy
facility: Novo Nordisk Investigational Site
city: Chieti Scalo
country: Italy
facility: Novo Nordisk Investigational Site
city: Firenze
country: Italy
facility: Novo Nordisk Investigational Site
city: Foggia
country: Italy
facility: Novo Nordisk Investigational Site
city: Gazi
country: Italy
facility: Novo Nordisk Investigational Site
city: Messina
country: Italy
facility: Novo Nordisk Investigational Site
city: Milano
country: Italy
facility: Novo Nordisk Investigational Site
city: Perugia
country: Italy
facility: Novo Nordisk Investigational Site
city: Pisa
country: Italy
facility: Novo Nordisk Investigational Site
city: Roma
country: Italy
facility: Novo Nordisk Investigational Site
city: Torino
country: Italy
facility: Novo Nordisk Investigational Site
city: Baia Mare
country: Romania
facility: Novo Nordisk Investigational Site
state: Maramures
city: Bucharest
country: Romania
facility: Novo Nordisk Investigational Site
city: Constanta
country: Romania
facility: Novo Nordisk Investigational Site
city: Suceava
country: Romania
facility: Novo Nordisk Investigational Site
city: Timisoara
country: Romania
facility: Novo Nordisk Investigational Site
city: Arkhangelsk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Barnaul
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Krasnoyarsk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Moscow
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Moscow
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Perm
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Yaroslavl
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Bratislava
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Bratislava
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Bratislava
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Lucenec
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Pretoria
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Durban
country: South Africa
facility: Novo Nordisk Investigational Site
state: KwaZulu-Natal
city: Durban
country: South Africa
facility: Novo Nordisk Investigational Site
state: KwaZulu-Natal
city: Bloemfontein
country: South Africa
facility: Novo Nordisk Investigational Site
city: Alcorcón
country: Spain
facility: Novo Nordisk Investigational Site
city: Almería
country: Spain
facility: Novo Nordisk Investigational Site
city: Barcelona
country: Spain
facility: Novo Nordisk Investigational Site
city: Granada
country: Spain
facility: Novo Nordisk Investigational Site
city: Hospitalet de Llobregat
country: Spain
facility: Novo Nordisk Investigational Site
city: La Coruña
country: Spain
facility: Novo Nordisk Investigational Site
city: Madrid
country: Spain
facility: Novo Nordisk Investigational Site
city: Mostoles - Madrid -
country: Spain
facility: Novo Nordisk Investigational Site
city: Sabadell
country: Spain
facility: Novo Nordisk Investigational Site
city: San Juan
country: Spain
facility: Novo Nordisk Investigational Site
city: Valencia
country: Spain
facility: Novo Nordisk Investigational Site
city: Antalya
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Mersin
country: Turkey
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: Heller S, Mathieu C, Kapur R, Wolden ML, Zinman B. A meta-analysis of rate ratios for nocturnal confirmed hypoglycaemia with insulin degludec vs. insulin glargine using different definitions for hypoglycaemia. Diabet Med. 2016 Apr;33(4):478-87. doi: 10.1111/dme.13002. Epub 2015 Dec 13.
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, Christensen T, Rana A, Bain SC. Insulin degludec versus insulin glargine in type 1 and type 2 diabetes mellitus: a meta-analysis of endpoints in phase 3a trials. Diabetes Ther. 2014 Dec;5(2):435-46. doi: 10.1007/s13300-014-0076-9. Epub 2014 Aug 1.
citation: Aye MM, Atkin SL. Patient safety and minimizing risk with insulin administration - role of insulin degludec. Drug Healthc Patient Saf. 2014 Apr 30;6:55-67. doi: 10.2147/DHPS.S59566. eCollection 2014.
citation: Garber AJ, King AB, Del Prato S, Sreenan S, Balci MK, Munoz-Torres M, Rosenstock J, Endahl LA, Francisco AM, Hollander P; NN1250-3582 (BEGIN BB T2D) Trial Investigators. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 2 diabetes (BEGIN Basal-Bolus Type 2): a phase 3, randomised, open-label, treat-to-target non-inferiority trial. Lancet. 2012 Apr 21;379(9825):1498-507. doi: 10.1016/S0140-6736(12)60205-0.
citation: Hollander P, King AB, Del Prato S, Sreenan S, Balci MK, Munoz-Torres M, Rosenstock J, Hansen CT, Niemeyer M, Garber AJ. Insulin degludec improves long-term glycaemic control similarly to insulin glargine but with fewer hypoglycaemic episodes in patients with advanced type 2 diabetes on basal-bolus insulin therapy. Diabetes Obes Metab. 2015 Feb;17(2):202-6. doi: 10.1111/dom.12411. Epub 2014 Nov 27.
citation: Freemantle N, Mamdani M, Vilsboll T, Kongso JH, Kvist K, Bain SC. IDegLira Versus Alternative Intensification Strategies in Patients with Type 2 Diabetes Inadequately Controlled on Basal Insulin Therapy. Diabetes Ther. 2015 Dec;6(4):573-591. doi: 10.1007/s13300-015-0142-y. Epub 2015 Nov 18.
citation: Evans M, Chubb B, Gundgaard J. Cost-effectiveness of Insulin Degludec Versus Insulin Glargine in Adults with Type 1 and Type 2 Diabetes Mellitus. Diabetes Ther. 2017 Apr;8(2):275-291. doi: 10.1007/s13300-017-0236-9. Epub 2017 Feb 16.