Efficacy and Safety of Basal-bolus Therapy, Comparing Stepwise Addition of Insulin Aspart Versus Complete Basal-bolus Regimen (Full STEP™)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT01165684
First received: July 16, 2010
Last updated: July 3, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Diabetes
Diabetes Mellitus, Type 2
Drug: insulin aspart
Drug: insulin detemir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novo Nordisk A/S:

Primary Outcome Measures:
  • Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 32 [ Time Frame: Week 0, Week 32 ] [ Designated as safety issue: No ]
    Estimated mean change from baseline in HbA1c after 32 Weeks of treatment


Secondary Outcome Measures:
  • Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 10 [ Time Frame: Week 0, Week 10 ] [ Designated as safety issue: No ]
    Estimated mean change from baseline in HbA1c after 10 Weeks of treatment

  • Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 21 [ Time Frame: Week 0, Week 21 ] [ Designated as safety issue: No ]
    Estimated mean change from baseline in HbA1c after 21 Weeks of treatment

  • Proportion of Subjects Reaching Glycosylated Haemoglobin (HbA1c) Below 7.0% at Week 10 [ Time Frame: Week 10 ] [ Designated as safety issue: No ]
    Proportion of subjects reaching HbA1c below 7.0% at Week 10

  • Proportion of Subjects Reaching Glycosylated Haemoglobin (HbA1c) Below 7.0% at Week 21 [ Time Frame: Week 21 ] [ Designated as safety issue: No ]
    Proportion of subjects reaching HbA1c below 7.0% at Week 21

  • Proportion of Subjects Reaching Glycosylated Haemoglobin (HbA1c) Below 7.0% at Week 32 [ Time Frame: Week 32 ] [ Designated as safety issue: No ]
    Proportion of subjects reaching HbA1c below 7.0% at Week 32

  • Fasting Plasma Glucose (FPG) at Week 10 [ Time Frame: Week 10 ] [ Designated as safety issue: No ]
    Mean FPG at Week 10

  • Fasting Plasma Glucose (FPG) at Week 21 [ Time Frame: Week 21 ] [ Designated as safety issue: No ]
    Mean FPG at Week 21

  • Fasting Plasma Glucose (FPG) at Week 32 [ Time Frame: Week 32 ] [ Designated as safety issue: No ]
    Estimated Mean FPG at Week 32

  • Mean Plasma Glucose Increment Over 3 Meals (Breakfast, Lunch and Dinner) at Week 10 [ Time Frame: Week 10 ] [ Designated as safety issue: No ]
    Mean plasma glucose increment over 3 meals (breakfast, lunch and dinner) at Week 10

  • Mean Plasma Glucose Increment Over 3 Meals (Breakfast, Lunch and Dinner) at Week 21 [ Time Frame: Week 21 ] [ Designated as safety issue: No ]
    Mean plasma glucose increment over 3 meals (breakfast, lunch and dinner) at Week 21

  • Mean Plasma Glucose Increment Over 3 Meals (Breakfast, Lunch and Dinner) at Week 32 [ Time Frame: Week 32 ] [ Designated as safety issue: No ]
    Estimated mean plasma glucose increment over 3 meals (breakfast, lunch and dinner) at Week 32

  • Body Weight at Week 32 [ Time Frame: Week 32 ] [ Designated as safety issue: No ]
    Estimated mean body weight after 32 Weeks of treatment

  • Body Mass Index (BMI) at Week 32 [ Time Frame: Week 32 ] [ Designated as safety issue: No ]
    Estimated mean BMI after 32 Weeks of treatment

  • Hypoglycaemic Episodes (Rate of All Treatment Emergent Hypoglycaemia Episodes) [ Time Frame: Week 0 to Week 32 ] [ Designated as safety issue: No ]
    A hypoglycaemic episode was defined as treatment emergent if the onset of the episode was on or after the first day of exposure to randomised treatment and no later than 1 day after the last day of randomised treatment.


Enrollment: 401
Study Start Date: October 2010
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Step-wise Drug: insulin aspart

Insulin aspart added stepwise according to the largest meal following an evaluation of HbA1c.

Doses individually adjusted.

Drug: insulin detemir
Insulin detemir as basal insulin, adminstered once daily. Doses individually adjusted.
Active Comparator: Basal-bolus Drug: insulin aspart
Insulin aspart added before each main meal. Doses individually adjusted.
Drug: insulin detemir
Insulin detemir as basal insulin, adminstered once daily. Doses individually adjusted.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01165684

  Show 37 Study Locations
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
Study Director: Gitte S. Olesen, MSc Pharm Novo Nordisk A/S
  More Information

Additional Information:
No publications provided by Novo Nordisk A/S

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01165684     History of Changes
Other Study ID Numbers: ANA-3786, 2010-018974-19, U1111-1116-0908
Study First Received: July 16, 2010
Results First Received: April 25, 2013
Last Updated: July 3, 2013
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia
Brazil: National Health Surveillance Agency
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Macedonia, The Former Yugoslav Republic of: Ministry of Health of Republic of Macedonia
Slovenia: Agency of Drugs and Medicinal Products of the Slovenian Republic
United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin aspart
Insulin
Hypoglycemic Agents
Insulin, Long-Acting
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014