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Comparison of NN1250 With Insulin Glargine Plus Insulin Aspart With/Without Metformin and With/Without Pioglitazone in Type 2 Diabetes (BEGIN™)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00972283
First Posted: September 4, 2009
Last Update Posted: April 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Novo Nordisk A/S
  Purpose

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.


Condition Intervention Phase
Diabetes Diabetes Mellitus, Type 2 Drug: insulin degludec Drug: insulin glargine Drug: insulin aspart Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Main Trial (Primary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 52 Weeks of Treatment [ Time Frame: Week 0, Week 52 ]
    Change from baseline in HbA1c after 52 weeks of treatment

  • Extension Trial (Primary Endpoint): Rate of Confirmed Hypoglycaemic Episodes [ Time Frame: Week 0 to Week 78 + 7 days follow up ]
    Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.

  • Extension Trial (Primary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes [ Time Frame: Week 0 to Week 78 + 7 days follow up ]
    Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes are defined as occurring between 00:01 and 05:59 a.m.

  • Rate of Treatment Emergent Adverse Events (AEs) [ Time Frame: Week 0 to Week 78 + 7 days follow up ]
    Corresponds to rate of AEs per 100 patient years of exposure. Mild AEs: no or transient symptoms, no interference with subject's daily activities. Moderate AEs: marked symptoms, moderate interference with subject's daily activities. Severe AEs: considerable interference with subject's daily activities, unacceptable. Serious adverse event (SAE): AE that at any dose results in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect.


Secondary Outcome Measures:
  • Extension Trial (Secondary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 78 Weeks of Treatment [ Time Frame: Week 0, Week 78 ]
    Change from baseline in HbA1c after 78 weeks of treatment

  • Main Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 52 [ Time Frame: Week 52 ]
    Mean of 9-point SMPG at 52 weeks of treatment. Plasma glucose measured: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime, at 4 am and before breakfast.

  • Extension Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 78 [ Time Frame: Week 78 ]
    Mean of the SMPG at 78 weeks of treatment. Plasma glucose measured: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime, at 4 am, before breakfast.

  • Main Trial (Secondary Endpoint): Rate of Confirmed Hypoglycaemic Episodes [ Time Frame: Week 0 to Week 52 + 7 days follow up ]
    Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.

  • Main Trial (Secondary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes [ Time Frame: Week 0 to Week 52 + 7 days follow up ]
    Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes are defined as occurring between 00:01 and 05:59 a.m.


Enrollment: 1006
Actual Study Start Date: September 1, 2009
Study Completion Date: October 28, 2010
Primary Completion Date: October 28, 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IDeg OD Drug: insulin degludec
Injected subcutaneously (under the skin) with main evening meal. Dose was individually adjusted.
Drug: insulin aspart
Injected subcutaneously (under the skin) at each main meal. Dose was individually adjusted.
Active Comparator: IGlar OD Drug: insulin glargine
Injected subcutanoeusly (under the skin) according to approved label. Dose was individually adjusted.
Drug: insulin aspart
Injected subcutaneously (under the skin) at each main meal. Dose was individually adjusted.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00972283


  Show 136 Study Locations
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
Study Director: Global Clinical Registry (GCR, 1452) Novo Nordisk A/S
  More Information

Additional Information:
Publications:
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.
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.
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.
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.
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. Review.
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.
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. Review.
Garber AJ, King AB, Del Prato S, Sreenan S, Balci MK, Muñoz-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.
Hollander P, King AB, Del Prato S, Sreenan S, Balci MK, Muñoz-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.
Freemantle N, Mamdani M, Vilsbøll T, Kongsø 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. Epub 2015 Nov 18.
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.

Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT00972283     History of Changes
Obsolete Identifiers: NCT01193322
Other Study ID Numbers: NN1250-3582
2008-005777-35 ( EudraCT Number )
U1111-1111-8648 ( Other Identifier: WHO )
2009-015816-17 ( EudraCT Number )
U1111-1114-9067 ( Other Identifier: WHO )
First Submitted: September 3, 2009
First Posted: September 4, 2009
Results First Submitted: October 14, 2015
Results First Posted: November 13, 2015
Last Update Posted: April 6, 2017
Last Verified: March 2017

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Pioglitazone
Insulin degludec, insulin aspart drug combination
Insulin
Metformin
Insulin Glargine
Insulin Aspart
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs


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