Comparison of Two NN1250 Formulations Versus Insulin Glargine, All in Combination With Metformin in Subjects With Type 2 Diabetes

A 16 Week Randomised, Open-labelled, Four-armed, Treat-to-target, Parallel-group Trial Comparing SIBA D Once Daily, SIBA E Once Daily, SIBA D Monday, Wednesday and Friday and Insulin Glargine Once Daily, All in Combination With Metformin in Subjects With Type 2 Diabetes Failing on OAD Treatment

This trial is conducted in Africa, Asia and North America. The aim of this trial is to compare two insulin degludec (NN1250, SIBA) formulations with each other and with insulin glargine, all in combination with metformin in insulin naive subjects with type 2 diabetes.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes
• Intervention / Treatment: Drug: insulin degludec; Drug: insulin degludec; Drug: insulin degludec; Drug: metformin; Drug: insulin glargine

• Study Type: Interventional
• Enrollment (Actual): 245
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Cambridge, Ontario, Canada, N1R 7L6
      • Novo Nordisk Investigational Site
    • Etobicoke, Ontario, Canada, M9R 4E1
      • Novo Nordisk Investigational Site
    • Toronto, Ontario, Canada, M5C 2T2
      • Novo Nordisk Investigational Site
    • Toronto, Ontario, Canada, M5T 3L9
      • Novo Nordisk Investigational Site
• India
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500082
      • Novo Nordisk Investigational Site
  • Kerala
    • Kochi, Kerala, India, 682041
      • Novo Nordisk Investigational Site
  • Maharashtra
    • Mumbai, Maharashtra, India, 400012
      • Novo Nordisk Investigational Site
  • Tamil Nadu
    • Vellore, Tamil Nadu, India, 632004
      • Novo Nordisk Investigational Site
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2001
      • Novo Nordisk Investigational Site
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4126
      • Novo Nordisk Investigational Site
    • Durban, KwaZulu-Natal, South Africa, 4001
      • Novo Nordisk Investigational Site
• United States
  • California
    • Inglewood, California, United States, 90301
      • Novo Nordisk Investigational Site
    • Los Angeles, California, United States, 90057
      • Novo Nordisk Investigational Site
    • Redlands, California, United States, 92374
      • Novo Nordisk Investigational Site
    • Spring Valley, California, United States, 91978
      • Novo Nordisk Investigational Site
  • Florida
    • Jacksonville, Florida, United States, 32204
      • Novo Nordisk Investigational Site
  • Idaho
    • Idaho Falls, Idaho, United States, 83404-7596
      • Novo Nordisk Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Novo Nordisk Investigational Site
    • Chicago, Illinois, United States, 60616
      • Novo Nordisk Investigational Site
    • Springfield, Illinois, United States, 62711
      • Novo Nordisk Investigational Site
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • Novo Nordisk Investigational Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • Novo Nordisk Investigational Site
  • South Carolina
    • Simpsonville, South Carolina, United States, 29681
      • Novo Nordisk Investigational Site
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Novo Nordisk Investigational Site
  • Texas
    • Dallas, Texas, United States, 75230
      • Novo Nordisk Investigational Site
    • San Antonio, Texas, United States, 78229
      • Novo Nordisk Investigational Site
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Novo Nordisk Investigational Site
  • Washington
    • Renton, Washington, United States, 98057
      • Novo Nordisk Investigational Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53209
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject.)
• Insulin naïve type 2 diabetes subjects (as diagnosed clinically) for at least 3 months (no previous insulin treatment or previous short term insulin treatment maximeum 14 days within the last 3 months)
• Treatment with one or two oral anti-diabetic drug (OADs): metformin, sulphonylurea (SU) (or other insulin secretagogue e.g. repaglinide, nateglinide), alpha-glucosidase inhibitors for at least 2 months at a stable maximally tolerated dose or at least half maximally allowed dose according to the summary of product characteristics (SPC) or locally approved PI
• HbA1c 7.0-11.0 % (both inclusive)
• Body Mass Index (BMI) 23-42 kg/m^2 [lb/in^2 x 703] (both inclusive)

Exclusion Criteria:

• Metformin contraindication according to local practice
• Thiazolidinedione (TZD) treatment within previous three months prior to visit 1
• Any systemic treatment with products which in the Investigator's opinion could interfere with glucose or lipid metabolism (e.g. systemic corticosteroids) three months prior to randomisation
• Subject has a clinically significant, active (during the past 12 months) disease of the gastrointestinal, pulmonary, neurological, genitourinary, or haematological system (except for conditions associated with type 2 diabetes) that, in the opinion of the Investigator, may confound the results of the trial or pose additional risk in administering trial drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SIBA (D)	Drug: insulin degludec; Formulation D: Treat-to-target dose titration scheme, s.c. injection, once daily; Drug: insulin degludec; Formulation E: Treat-to-target dose titration scheme, s.c. injection, once daily; Drug: insulin degludec; Formulation D: Treat-to-target dose titration scheme, s.c. injection, 3 times weekly; Drug: metformin; Tablets, 1500-2000 mg/day
EXPERIMENTAL: SIBA (E)	Drug: insulin degludec; Formulation D: Treat-to-target dose titration scheme, s.c. injection, once daily; Drug: insulin degludec; Formulation E: Treat-to-target dose titration scheme, s.c. injection, once daily; Drug: insulin degludec; Formulation D: Treat-to-target dose titration scheme, s.c. injection, 3 times weekly; Drug: metformin; Tablets, 1500-2000 mg/day
EXPERIMENTAL: SIBA (D) M, W, F	Drug: insulin degludec; Formulation D: Treat-to-target dose titration scheme, s.c. injection, once daily; Drug: insulin degludec; Formulation E: Treat-to-target dose titration scheme, s.c. injection, once daily; Drug: insulin degludec; Formulation D: Treat-to-target dose titration scheme, s.c. injection, 3 times weekly; Drug: metformin; Tablets, 1500-2000 mg/day
ACTIVE_COMPARATOR: IGlar	Drug: metformin; Tablets, 1500-2000 mg/day; Drug: insulin glargine; Treat-to-target dose titration scheme, s.c. injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Glycosylated Haemoglobin (HbA1c)	Change from baseline in HbA1c after 16 weeks of treatment	Week 0, Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean of 9-point Self Measured Plasma Glucose Profile (SMPG)	Mean of SMPG after 16 weeks of treatment. Plasma glucose measured: before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner, before bedtime, at 4 am and before breakfast.	Week 16
Rate of Major and Minor Hypoglycaemic Episodes	Rate of major and minor hypoglycaemic episodes per 100 patient years of exposure (PYE). Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L.	Week 0 to Week 16 + 5 days follow up
Rate of Nocturnal Major and Minor Hypoglycaemic Episodes	Rate of nocturnal major and minor hypoglycaemic episodes per 100 patient years of exposure (PYE). Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Episodes were defined as nocturnal if the time of onset was between 23:00 (included) and 05:59 (included).	Week 0 to Week 16 + 5 days follow up
Rate of Treatment Emergent Adverse Events (AEs)	Corresponds to rate of AEs per 100 patient years of exposure. Severity assessed by investigator. Mild: no or transient symptoms, no interference with subject's daily activities. Moderate: marked symptoms, moderate interference with subject's daily activities. Severe: considerable interference with subject's daily activities, unacceptable. Serious AE: 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.	Week 0 to Week 16 + 5 days follow up
Laboratory Safety Parameters (Biochemistry): Alanine Aminotransferase (ALAT)	Mean values at Week -4 and at Week 16	Week -4, Week 16
Laboratory Safety Parameters (Biochemistry): Aspartate Aminotransferase (ASAT)	Mean values at Week -4 and at Week 16	Week -4, Week 16
Laboratory Safety Parameters (Biochemistry): Serum Creatinine	Mean values at Week -4 and at Week 16	Week -4, Week 16
Vital Signs: Diastolic Blood Pressure (BP)	Mean values at baseline (Week 0) and at Week 16	Week 0, Week 16
Vital Signs: Systolic Blood Pressure (BP)	Mean values at baseline (Week 0) and at Week 16	Week 0, Week 16
Vital Signs: Pulse	Mean values at baseline (Week 0) and at Week 16	Week 0, Week 16
Physical Examination	Physical examination was performed at screening (Week -4), randomisation (Week 0) and after 8 and 16 weeks of treatment. If any new findings or deterioration in previous findings were observed during the trial, these were recorded as AEs and are therefore not presented separately as no analysis was performed.	Week -4, Week 0, Week 8, Week 16

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Zinman B, Fulcher G, Rao PV, Thomas N, Endahl LA, Johansen T, Lindh R, Lewin A, Rosenstock J, Pinget M, Mathieu C. Insulin degludec, an ultra-long-acting basal insulin, once a day or three times a week versus insulin glargine once a day in patients with type 2 diabetes: a 16-week, randomised, open-label, phase 2 trial. Lancet. 2011 Mar 12;377(9769):924-31. doi: 10.1016/S0140-6736(10)62305-7.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (ACTUAL): August 1, 2008
• Study Completion (ACTUAL): August 1, 2008

Study Registration Dates

• First Submitted: January 29, 2008
• First Submitted That Met QC Criteria: February 8, 2008
• First Posted (ESTIMATE): February 11, 2008

Study Record Updates

• Last Update Posted (ACTUAL): March 3, 2017
• Last Update Submitted That Met QC Criteria: January 19, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin, Long-Acting; Metformin; Insulin Glargine
• Other Study ID Numbers: NN1250-1836