Clinical trial NCT01068665: Comparison of NN1250 With Insulin Glargine in Subjects With Type 2 Diabetes
Official title: A Trial Comparing Efficacy and Safety of NN1250 and Insulin Glargine in Subjects With Type 2 Diabetes (BEGIN™: LOW VOLUME)
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: 2010-02-15
Enrollment: 460
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 South Africa, Europe and North America. The aim of this trial is to compare efficacy and safety of NN1250 (insulin degludec (IDeg)) with insulin glargine (IGlar), as add-on to subject's ongoing treatment with metformin and/or dipeptyl peptidase 4 (DPP-4) inhibitors, in patients with type 2 diabetes being treated with oral anti-diabetic drugs (OADs) qualifying for intensified treatment.


Eligibility criteria: Inclusion Criteria:

* Insulin naïve subject (allowed are: previous short term insulin treatment up to 14 days; Treatment during hospitalisation or during gestational diabetes is allowed for periods longer than 14 days)
* Current treatment: metformin monotherapy or metformin in any combination with an insulin secretagogue (sulfonylurea or glinide), DPP-4 inhibitor, alpha-glucosidase-inhibitors (acarbose) with unchanged dosing for at least 3 months prior to visit 1 with the minimum doses stated: -Metformin: alone or in combination (including fixed combination) 1500 mg daily, or maximum tolerated dose (at least 1000 mg daily) -Insulin secretagogue (sulfonylurea or glinide): minimum half of the daily maximal dose according to local labelling -DPP-4 inhibitor: minimum half of the daily maximal dose according to local labelling - alpha-glucosidase-inhibitors (acarbose): minimum half of the daily maximal dose or maximum tolerated dose
* HbA1c 7.0-10.0 % (both inclusive) by central laboratory analysis
* Body Mass Index (BMI) maximum 45.0 kg/m\^2
* Type 2 diabetes (diagnosed clinically) for at least 6 months
* Ability and willingness to adhere to the protocol including performance of self monitored plasma glucose (SMPG) profiles according to the protocol

Exclusion Criteria:

* Use within the last 3 months prior to Visit 1 of: thiazoledinediones (TZDs), exenatide or liraglutide
* Cardiovascular disease, within the last 6 months prior to Visit 1, defined as: stroke; decompensated heart failure New York Heart Association (NYHA) class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty
* Uncontrolled treated/untreated severe hypertension (systolic blood pressure at least 180 millimetre (mm) mercury (Hg) and/or diastolic blood pressure at least 100 mmHg)
* Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures according to local requirements \[for UK: adequate contraceptive measures are defined as established use of oral, injected or implanted hormonal methods of contraception, sterilisation, intrauterine device or intrauterine system, or consistent use of barrier methods\]
* Cancer and medical history of cancer hereof (except basal cell skin cancer or squamous cell skin cancer)

Primary outcomes:
measure: Change in Glycosylated Haemoglobin (HbA1c)
timeFrame: Week 0, Week 26
Secondary outcomes:
measure: Change in Fasting Plasma Glucose (FPG)
timeFrame: Week 0, Week 26
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Gilbert
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Tucson
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: Mission Hills
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Montclair
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: National City
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Norco
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: San Diego
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Valencia
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Walnut Creek
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Aurora
country: United States
facility: Novo Nordisk Investigational Site
state: Colorado
city: Hollywood
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Longwood
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Ocala
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Ponte Vedra
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Vero Beach
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Decatur
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Lawrenceville
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Roswell
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Chicago
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Chicago
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Crystal Lake
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Evansville
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Greenfield
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Des Moines
country: United States
facility: Novo Nordisk Investigational Site
state: Iowa
city: Madisonville
country: United States
facility: Novo Nordisk Investigational Site
state: Kentucky
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: Brockton
country: United States
facility: Novo Nordisk Investigational Site
state: Massachusetts
city: Southfield
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Southfield
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Troy
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Minneapolis
country: United States
facility: Novo Nordisk Investigational Site
state: Minnesota
city: Biloxi
country: United States
facility: Novo Nordisk Investigational Site
state: Mississippi
city: St. Louis
country: United States
facility: Novo Nordisk Investigational Site
state: Missouri
city: Billings
country: United States
facility: Novo Nordisk Investigational Site
state: Montana
city: Brick
country: United States
facility: Novo Nordisk Investigational Site
state: New Jersey
city: Mine Hill
country: United States
facility: Novo Nordisk Investigational Site
state: New Jersey
city: Brooklyn
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: New York
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: Chapel Hill
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: Greensboro
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Franklin
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Beaver
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Melrose Park
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Norristown
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Peak
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Desoto
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: El Paso
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Killeen
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Plano
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Sugar Land
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: St. George
country: United States
facility: Novo Nordisk Investigational Site
state: Utah
city: Renton
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Milwaukee
country: United States
facility: Novo Nordisk Investigational Site
state: Wisconsin
city: Calgary
country: Canada
facility: Novo Nordisk Investigational Site
state: Alberta
city: Edmonton
country: Canada
facility: Novo Nordisk Investigational Site
state: Alberta
city: Langley
country: Canada
facility: Novo Nordisk Investigational Site
state: British Columbia
city: Cambridge
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Cornwall
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Hamilton
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Hamilton
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Hamilton
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Mississauga
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Sudbury
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: St. Romuald
country: Canada
facility: Novo Nordisk Investigational Site
state: Quebec
city: Antibes
country: France
facility: Novo Nordisk Investigational Site
city: Besancon
country: France
facility: Novo Nordisk Investigational Site
city: Narbonne
country: France
facility: Novo Nordisk Investigational Site
city: Pointe à Pitre
country: France
facility: Novo Nordisk Investigational Site
city: Rennes
country: France
facility: Novo Nordisk Investigational Site
city: Sète
country: France
facility: Novo Nordisk Investigational Site
city: Venissieux
country: France
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: Ekaterinburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Kemerovo
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: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Voronezh
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: East London
country: South Africa
facility: Novo Nordisk Investigational Site
state: Eastern Cape
city: Port Elizabeth
country: South Africa
facility: Novo Nordisk Investigational Site
state: Eastern Cape
city: Durban
country: South Africa
facility: Novo Nordisk Investigational Site
state: KwaZulu-Natal
city: Alberton
country: South Africa
facility: Novo Nordisk Investigational Site
city: Kiev
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Abergavenny
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Ashton-Under-Lyne
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Atherstone
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Ayr
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Bath
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Bolton
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Chester
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Chorley
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Coventry
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Epworth
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Harrogate
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Letchworth
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Livingstone
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Llantrisant
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Maidstone
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Oldham
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Rugby
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Salford
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Trowbridge
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Whitby
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Wrexham
country: United Kingdom
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR, 1452)
role: STUDY_DIRECTOR
References:
citation: Weatherall J, Bloudek L, Buchs S. Budget impact of treating commercially insured type 1 and type 2 diabetes patients in the United States with insulin degludec compared to insulin glargine. Curr Med Res Opin. 2017 Feb;33(2):231-238. doi: 10.1080/03007995.2016.1251893. Epub 2016 Nov 18.
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: Gough SC, Bhargava A, Jain R, Mersebach H, Rasmussen S, Bergenstal RM. Low-volume insulin degludec 200 units/ml once daily improves glycemic control similarly to insulin glargine with a low risk of hypoglycemia in insulin-naive patients with type 2 diabetes: a 26-week, randomized, controlled, multinational, treat-to-target trial: the BEGIN LOW VOLUME trial. Diabetes Care. 2013 Sep;36(9):2536-42. doi: 10.2337/dc12-2329. Epub 2013 May 28.
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: 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: 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.