Clinical trial NCT01165684: Efficacy and Safety of Basal-bolus Therapy, Comparing Stepwise Addition of Insulin Aspart Versus Complete Basal-bolus Regimen
Official title: A Randomised, Controlled, Open Label, Multicentre, Multinational, Treat-to-target Trial Investigating the Efficacy and Safety of Intensification With Addition of Bolus Insulin Aspart in Subjects With Type 2 Diabetes Inadequately Controlled on Basal Insulin With or Without Oral Anti-diabetic Drugs: Step-wise Addition Versus Complete Basal-bolus Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2010-07-20
Enrollment: 401
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 North and South America. The aim of this clinical trial is to investigate if the two treatments are equally effective.


Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes (diagnosed clinically) for at least 12 months
* Basal insulin treatment (NPH once or twice daily, insulin glargine once daily or insulin detemir once daily) for at least 6 months
* HbA1c: 7.0-9.0 % (both inclusive) by central laboratory analysis (one retest analysed at the central laboratory within a week is permitted with the result of the last sample being conclusive)
* BMI (Body Mass Index) less than 40.0 kg/m\^2

Exclusion Criteria:

* Previous use of pre-mix or bolus insulin (allowed is previous use of bolus insulin only in case of a hospitalisation or a severe condition requiring intermittent use of bolus insulin for less than 14 consecutive days, but not during the last 6 months prior to screening visit (Visit 1)
* Use of GLP-1 (Glucagon-like peptide-1) receptor agonists or pramlintide within the last 6 months prior to prior to screening visit (Visit 1)
* Anticipated change in concomitant medication known to interfere significantly with glucose metabolism (e.g. systemic corticosteroids, beta-blockers, MAO (Monoamine oxidase) inhibitors, etc.)
* Cardiovascular disease, within the last 12 months prior to screening visit (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 sitting at least 180 millimetre (mm) mercury (Hg) and/or diastolic blood pressure at least 100 mmHg). For Argentina: systolic blood pressure sitting at least 150 mmHg and/or diastolic blood pressure at least 90 mmHg
* Impaired liver function, defined as ALAT (Alanine aminotransferase) at least 2.5 times upper limit of normal (one retest analysed at the central laboratory within a week is permitted with the result of the last sample being conclusive)
* Impaired renal function defined as serum creatinine above 135 micromol/L (above 1.5 mg/dL) for males and above 110 micromol/L (above 1.2 mg/dL) for females; and, if required by the locally applicable metformin label, glomerular filtration rate below 60 ml/min, calculated by the Cockroft \& Gault formula). One retest within a week is permitted with the result of the last sample being conclusive
* Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic episode, during the last 12 months) or hypoglycaemic unawareness as judged by the Investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months
* Proliferative retinopathy or maculopathy requiring treatment according to the Investigator
* Treatment with OADs (Oral anti-diabetic drug) contraindicated or unapproved for combination treatment with insulin (according to local OAD label)

Primary outcomes:
measure: Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 32
timeFrame: Week 0, Week 32
Secondary outcomes:
measure: Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 10
timeFrame: Week 0, Week 10
measure: Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 21
timeFrame: Week 0, Week 21
measure: Proportion of Subjects Reaching Glycosylated Haemoglobin (HbA1c) Below 7.0% at Week 10
timeFrame: Week 10
measure: Proportion of Subjects Reaching Glycosylated Haemoglobin (HbA1c) Below 7.0% at Week 21
timeFrame: Week 21
measure: Proportion of Subjects Reaching Glycosylated Haemoglobin (HbA1c) Below 7.0% at Week 32
timeFrame: Week 32
measure: Fasting Plasma Glucose (FPG) at Week 10
timeFrame: Week 10
measure: Fasting Plasma Glucose (FPG) at Week 21
timeFrame: Week 21
measure: Fasting Plasma Glucose (FPG) at Week 32
timeFrame: Week 32
measure: Mean Plasma Glucose Increment Over 3 Meals (Breakfast, Lunch and Dinner) at Week 10
timeFrame: Week 10
measure: Mean Plasma Glucose Increment Over 3 Meals (Breakfast, Lunch and Dinner) at Week 21
timeFrame: Week 21
measure: Mean Plasma Glucose Increment Over 3 Meals (Breakfast, Lunch and Dinner) at Week 32
timeFrame: Week 32
measure: Body Weight at Week 32
timeFrame: Week 32
measure: Body Mass Index (BMI) at Week 32
timeFrame: Week 32
measure: Hypoglycaemic Episodes (Rate of All Treatment Emergent Hypoglycaemia Episodes)
timeFrame: Week 0 to Week 32
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Mesa
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Scottsdale
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Fresno
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Hialeah
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Kissimmee
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: Plantation
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Port Charlotte
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Atlanta
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: Indianapolis
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Metairie
country: United States
facility: Novo Nordisk Investigational Site
state: Louisiana
city: Rockville
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Springfield
country: United States
facility: Novo Nordisk Investigational Site
state: Massachusetts
city: Brooklyn Center
country: United States
facility: Novo Nordisk Investigational Site
state: Minnesota
city: Jefferson City
country: United States
facility: Novo Nordisk Investigational Site
state: Missouri
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: New Windsor
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Beavercreek
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Dayton
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Kettering
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Altoona
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Greer
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Dallas
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: Salt Lake City
country: United States
facility: Novo Nordisk Investigational Site
state: Utah
city: Newport News
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Buenos Aires
country: Argentina
facility: Novo Nordisk Investigational Site
city: Buenos Aires
country: Argentina
facility: Novo Nordisk Investigational Site
city: Buenos Aires
country: Argentina
facility: Novo Nordisk Investigational Site
city: Buenos Aires
country: Argentina
facility: Novo Nordisk Investigational Site
city: Caba
country: Argentina
facility: Novo Nordisk Investigational Site
city: Córdoba
country: Argentina
facility: Novo Nordisk Investigational Site
city: Mendoza
country: Argentina
facility: Novo Nordisk Investigational Site
city: Goiania
country: Brazil
facility: Novo Nordisk Investigational Site
state: Goias
city: São Paulo
country: Brazil
facility: Novo Nordisk Investigational Site
state: Sao Paulo
city: Campinas
country: Brazil
facility: Novo Nordisk Investigational Site
city: Porto Alegre
country: Brazil
facility: Novo Nordisk Investigational Site
city: Rio de Janeiro
country: Brazil
facility: Novo Nordisk Investigational Site
city: Calgary
country: Canada
facility: Novo Nordisk Investigational Site
state: Alberta
city: Coquitlam
country: Canada
facility: Novo Nordisk Investigational Site
state: British Columbia
city: Langley
country: Canada
facility: Novo Nordisk Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: Novo Nordisk Investigational Site
state: British Columbia
city: Victoria
country: Canada
facility: Novo Nordisk Investigational Site
state: British Columbia
city: Chatham
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Kingston
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Gatineau
country: Canada
facility: Novo Nordisk Investigational Site
state: Quebec
city: Lachine
country: Canada
facility: Novo Nordisk Investigational Site
state: Quebec
city: Mirabel
country: Canada
facility: Novo Nordisk Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: Novo Nordisk Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: Novo Nordisk Investigational Site
state: Quebec
city: Marseille
country: France
facility: Novo Nordisk Investigational Site
city: Narbonne
country: France
facility: Novo Nordisk Investigational Site
city: Saint Herblain
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: Skopje
country: Macedonia, The Former Yugoslav Republic of
facility: Novo Nordisk Investigational Site
city: Brezice
country: Slovenia
facility: Novo Nordisk Investigational Site
city: Kranj
country: Slovenia
facility: Novo Nordisk Investigational Site
city: Novo mesto
country: Slovenia
facility: Novo Nordisk Investigational Site
city: Trbovlje
country: Slovenia
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR, 1452)
role: STUDY_DIRECTOR
References:
citation: Rodbard HW, Visco VE, Andersen H, Hiort LC, Shu DH. Treatment intensification with stepwise addition of prandial insulin aspart boluses compared with full basal-bolus therapy (FullSTEP Study): a randomised, treat-to-target clinical trial. Lancet Diabetes Endocrinol. 2014 Jan;2(1):30-7. doi: 10.1016/S2213-8587(13)70090-1. Epub 2013 Sep 25.