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CompletedNCT00614055Updated Mar 20, 2017Results posted

Comparison of Two NN5401 Formulations Versus Insulin Glargine, All in Combination With Metformin in Subjects With Type 2 Diabetes

A Phase 2 interventional study of insulin degludec/insulin aspart and insulin degludec/insulin aspart in Diabetes and Diabetes Mellitus, Type 2, sponsored by Novo Nordisk A/S. Completed at 28 sites in 5 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2017-03-20.

Sponsored by Novo Nordisk A/S · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
178
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

This trial is conducted in Europe. The aim of this trial is to compare two NN5401 (SIAC, insulin degludec/insulin aspart) formulations with each other and with insulin glargine, all in combination with metformin in insulin naive subjects with type 2 diabetes.

02

Conditions studied

  • Diabetes
  • Diabetes Mellitus, Type 2
03

In context

Diabetes Mellitus

10,925 studies on the registry are indexed under Diabetes Mellitus; 1,319 are open to participants now.

This study's enrollment of 178 is above the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.

Browse Diabetes Mellitus studies →

Lead sponsor

Novo Nordisk A/S is the lead sponsor of 1,370 studies on the registry; 102 are open to participants now.

Of its 198 completed or terminated interventional studies of FDA-regulated products, 94 (47%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

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 maximum 14 days within the last 3 months)
  • Treatment with one or two oral anti-diabetic drugs (OADs): metformin, sulfonylurea, other insulin secretagogue (e.g. repaglinide, nateglinide), alpha-glucosidase inhibitors for at least 2 month at a stable maximum tolerated dose or at least half maximum allowed dose according to locally approved summary of product characteristics (SPC)
  • HbA1c, 7.0 - 11.0 % (both inclusive)
  • Body Mass Index (BMI), 25.0 - 37.0 kg/m\^2 (both inclusive)

Exclusion criteria

Exclusion Criteria:

  • Metformin contraindication according to local practice
  • Thiazolidinedione (TZD) treatments within the 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) within 3 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 that, in the opinion of the investigator, may confound the results of the trial or pose additional risk in administering trial product
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
178 participants (actual)

Study arms

  • Active comparator
    Insulin glargine

    Drug: insulin glargine · Drug: metformin

  • Experimental
    SIAC 30 (B)

    Drug: insulin degludec/insulin aspart · Drug: metformin

  • Experimental
    SIAC 45 (B)

    Drug: insulin degludec/insulin aspart · Drug: metformin

Interventions

  • Druginsulin degludec/insulin aspart

    Formulation 1: Treat-to-target dose titration scheme, injection s.c., once daily

  • Druginsulin degludec/insulin aspart

    Formulation 2: Treat-to-target dose titration scheme, injection s.c., once daily

  • Druginsulin glargine

    Treat-to-target dose titration scheme, injection s.c., once daily

  • Drugmetformin

    Tablets, 1500-2000 mg/day

06

What researchers measure

Primary outcomes

  1. Change in Glycosylated Haemoglobin (HbA1c)

    Change from baseline in HbA1c after 16 weeks of treatment

    Time frame: Week 0, Week 16

Secondary outcomes

  1. Change in Fasting Plasma Glucose (FPG)

    Change from baseline in FPG after 16 weeks of treatment

    Time frame: Week 0, Week 16

  2. 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, bedtime, at 4 am and before breakfast.

    Time frame: Week 16

  3. 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.

    Time frame: Week 0 to Week 16 + 5 days follow up

  4. 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.

    Time frame: Week 0 to Week 16 + 5 days follow up

  5. 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 06:00 (excluded).

    Time frame: Week 0 to Week 16 + 5 days follow up

  6. Laboratory Safety Parameters (Biochemistry): Alanine Aminotransferase (ALAT)

    Values at screening (Week -4) and at Week 16

    Time frame: Week -4, Week 16

  7. Laboratory Safety Parameters (Biochemistry): Aspartate Aminotransferase (ASAT)

    Values at screening (Week -4) and at Week 16

    Time frame: Week -4, Week 16

  8. Laboratory Safety Parameters (Biochemistry): Serum Creatinine

    Values at screening (Week -4) and at Week 16

    Time frame: Week -4, Week 16

  9. Vital Signs: Diastolic Blood Pressure (BP)

    Values at baseline (Week 0) and at Week 16

    Time frame: Week 0, Week 16

  10. Vital Signs: Systolic Blood Pressure (BP)

    Values at baseline (Week 0) and at Week 16

    Time frame: Week 0, Week 16

  11. Vital Signs: Pulse

    Values at baseline (Week 0) and at Week 16

    Time frame: Week 0, Week 16

  12. Physical Examination

    Physical examination is performed at baseline (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.

    Time frame: Week 0, Week 8, Week 16

07

Results

Posted Nov 17, 2015

Participant flow

The trial was conducted at 22 sites in 5 countries: France (4 sites), Germany (5 sites), Norway (5 sites), Romania (3 sites) and Spain (5 sites).

Participant flow — Overall Study
MilestoneSIAC 30 (B)SIAC 45 (B)Insulin Glargine
Started595960
Exposed595960
Completed555355
Not completed465
Withdrew: Adverse event100
Withdrew: Protocol violation221
Withdrew: Lack of efficacy002
Withdrew: Unclassified142

Outcome measures

PrimaryChange in Glycosylated Haemoglobin (HbA1c)

Change from baseline in HbA1c after 16 weeks of treatment

Time frame:
Week 0, Week 16
Reported as:
Mean · percentage of glycosylated haemoglobin
Change in Glycosylated Haemoglobin (HbA1c)
percentage of glycosylated haemoglobinSIAC 30 (B)SIAC 45 (B)Insulin Glargine
Change in Glycosylated Haemoglobin (HbA1c)-1.31 ± 1.01-1.46 ± 1.39-1.29 ± 1.10
SecondaryChange in Fasting Plasma Glucose (FPG)

Change from baseline in FPG after 16 weeks of treatment

Time frame:
Week 0, Week 16
Reported as:
Mean · mmol/L
Change in Fasting Plasma Glucose (FPG)
mmol/LSIAC 30 (B)SIAC 45 (B)Insulin Glargine
Change in Fasting Plasma Glucose (FPG)-4.30 ± 3.45-4.10 ± 3.09-5.07 ± 3.85
SecondaryMean 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, bedtime, at 4 am and before breakfast.

Time frame:
Week 16
Reported as:
Mean · mmol/L
Mean of 9-point Self Measured Plasma Glucose Profile (SMPG)
mmol/LSIAC 30 (B)SIAC 45 (B)Insulin Glargine
Mean of 9-point Self Measured Plasma Glucose Profile (SMPG)8.34 ± 0.758.31 ± 0.788.42 ± 0.78
SecondaryRate 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.

Time frame:
Week 0 to Week 16 + 5 days follow up
Reported as:
Number · Events/100 years of patient exposure
Rate of Treatment Emergent Adverse Events (AEs)
Events/100 years of patient exposureSIAC 30 (B)SIAC 45 (B)Insulin Glargine
Adverse events (AEs)441310295
Serious AEs1160
Severe AEs600
Moderate AEs13812361
Mild AEs298187234
Fatal AEs000
SecondaryRate 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.

Time frame:
Week 0 to Week 16 + 5 days follow up
Reported as:
Number · Episodes/100 years of patient exposure
Rate of Major and Minor Hypoglycaemic Episodes
Episodes/100 years of patient exposureSIAC 30 (B)SIAC 45 (B)Insulin Glargine
Major000
Minor11524067
SecondaryRate 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 06:00 (excluded).

Time frame:
Week 0 to Week 16 + 5 days follow up
Reported as:
Number · Episodes/100 years of patient exposure
Rate of Nocturnal Major and Minor Hypoglycaemic Episodes
Episodes/100 years of patient exposureSIAC 30 (B)SIAC 45 (B)Insulin Glargine
Major000
Minor615817
SecondaryLaboratory Safety Parameters (Biochemistry): Alanine Aminotransferase (ALAT)

Values at screening (Week -4) and at Week 16

Time frame:
Week -4, Week 16
Reported as:
Mean · IU/L
Laboratory Safety Parameters (Biochemistry): Alanine Aminotransferase (ALAT)
IU/LSIAC 30 (B)SIAC 45 (B)Insulin Glargine
Week -4 , N=58, 59, 6031.9 ± 18.329.7 ± 15.333.7 ± 23.1
Week 16 , N=54, 54, 5723.9 ± 13.123.2 ± 9.722.3 ± 10.3
SecondaryLaboratory Safety Parameters (Biochemistry): Aspartate Aminotransferase (ASAT)

Values at screening (Week -4) and at Week 16

Time frame:
Week -4, Week 16
Reported as:
Mean · IU/L
Laboratory Safety Parameters (Biochemistry): Aspartate Aminotransferase (ASAT)
IU/LSIAC 30 (B)SIAC 45 (B)Insulin Glargine
Week -4, N=58, 59, 6024.8 ± 14.622.0 ± 8.324.0 ± 14.1
Week 16, N=54, 54, 5721.1 ± 8.220.0 ± 5.819.2 ± 6.4
SecondaryLaboratory Safety Parameters (Biochemistry): Serum Creatinine

Values at screening (Week -4) and at Week 16

Time frame:
Week -4, Week 16
Reported as:
Mean · umol/L
Laboratory Safety Parameters (Biochemistry): Serum Creatinine
umol/LSIAC 30 (B)SIAC 45 (B)Insulin Glargine
Week -4 , N=58, 59, 6076.4 ± 15.475.8 ± 14.477.4 ± 13.9
Week 16 , N=54, 54, 5775.7 ± 15.474.9 ± 15.676.8 ± 14.6
SecondaryVital Signs: Diastolic Blood Pressure (BP)

Values at baseline (Week 0) and at Week 16

Time frame:
Week 0, Week 16
Reported as:
Mean · mmHg
Vital Signs: Diastolic Blood Pressure (BP)
mmHgSIAC 30 (B)SIAC 45 (B)Insulin Glargine
Week 0 (Baseline), N=59, 59, 6078 ± 878 ± 879 ± 8
Week 16, N=56, 53, 5876 ± 877 ± 977 ± 7
SecondaryVital Signs: Systolic Blood Pressure (BP)

Values at baseline (Week 0) and at Week 16

Time frame:
Week 0, Week 16
Reported as:
Mean · mmHg
Vital Signs: Systolic Blood Pressure (BP)
mmHgSIAC 30 (B)SIAC 45 (B)Insulin Glargine
Week 0 (Baseline), N=59, 59, 60135 ± 15133 ± 14135 ± 15
Week 16, N=56, 53, 58129 ± 13133 ± 12129 ± 12
SecondaryVital Signs: Pulse

Values at baseline (Week 0) and at Week 16

Time frame:
Week 0, Week 16
Reported as:
Mean · beats/minute
Vital Signs: Pulse
beats/minuteSIAC 30 (B)SIAC 45 (B)Insulin Glargine
Week 0 (Baseline), N=59, 59, 6073 ± 1075 ± 1075 ± 9
Week 16, N=56, 53, 5871 ± 1069 ± 971 ± 11
SecondaryPhysical Examination

Physical examination is performed at baseline (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.

Time frame:
Week 0, Week 8, Week 16

No measurements were reported for this outcome.

Adverse events

Collected over The adverse events were collected in a time frame of 16 weeks + 7 days follow up. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
SIAC 30 (B)—2/59 (3.4%)23/59 (39%)
SIAC 45 (B)—1/59 (1.7%)16/59 (27.1%)
Insulin Glargine—0/60 (0%)13/60 (21.7%)
Most frequent serious events
Most frequent serious events
EventSIAC 30 (B)SIAC 45 (B)Insulin Glargine
Transient ischaemic attackNervous system disorders1/590/590/60
DepressionPsychiatric disorders1/590/590/60
EpistaxisRespiratory, thoracic and mediastinal disorders0/591/590/60
Most frequent other events
Most frequent other events
EventSIAC 30 (B)SIAC 45 (B)Insulin Glargine
C-reactive protein increasedInvestigations14/595/599/60
DyslipidaemiaMetabolism and nutrition disorders6/594/596/60
NasopharyngitisInfections and infestations4/593/591/60
DyspepsiaGastrointestinal disorders3/592/591/60
NauseaGastrointestinal disorders1/593/590/60
InfluenzaInfections and infestations0/592/593/60

Baseline characteristics

Age, Continuous
Age, Continuous(years)SIAC 30 (B)SIAC 45 (B)Insulin GlargineTotal
Mean58.7 ± 8.860.2 ± 8.458.4 ± 8.459.1 ± 8.5
Sex: Female, Male
Sex: Female, Male(Participants)SIAC 30 (B)SIAC 45 (B)Insulin GlargineTotal
Female22251663
Male373444115
Glycosylated haemoglobin (HbA1c)
Glycosylated haemoglobin (HbA1c)(percentage of glycosylated haemoglobin)SIAC 30 (B)SIAC 45 (B)Insulin GlargineTotal
Mean8.3 ± 1.28.6 ± 1.58.4 ± 1.38.5 ± 1.3
Fasting plasma glucose (FPG)
Fasting plasma glucose (FPG)(mmol/L)SIAC 30 (B)SIAC 45 (B)Insulin GlargineTotal
Mean11.1 ± 3.311.5 ± 3.212.1 ± 3.511.6 ± 3.3
08

Study locations

28 sites
  • Novo Nordisk Investigational Site
    Alès, 30100, France
  • Novo Nordisk Investigational Site
    Brest, 29609, France
  • Novo Nordisk Investigational Site
    LA ROCHELLE cedex, 17019, France
  • Novo Nordisk Investigational Site
    Le Creusot, 71200, France
  • Novo Nordisk Investigational Site
    Mont de Marsan, 40024, France
  • Novo Nordisk Investigational Site
    Venissieux, 69200, France
  • Novo Nordisk Investigational Site
    Bad Kreuznach, 55545, Germany
  • Novo Nordisk Investigational Site
    Bad Mergentheim, 97980, Germany
  • Novo Nordisk Investigational Site
    Dormagen, 41539, Germany
  • Novo Nordisk Investigational Site
    Hohenmölsen, 06679, Germany
  • Novo Nordisk Investigational Site
    Neuss, 41460, Germany
  • Novo Nordisk Investigational Site
    Neuwied, 56564, Germany
  • Novo Nordisk Investigational Site
    Elverum, 2408, Norway
  • Novo Nordisk Investigational Site
    Hamar, 2317, Norway
  • Novo Nordisk Investigational Site
    Kongsvinger, 2212, Norway
  • Novo Nordisk Investigational Site
    Oslo, 0586, Norway
  • Novo Nordisk Investigational Site
    Stavanger, 4011, Norway
  • Novo Nordisk Investigational Site
    Tromsø, 9038, Norway
  • Novo Nordisk Investigational Site
    Bucharest, 011234, Romania
  • Novo Nordisk Investigational Site
    Bucharest, 020042, Romania
  • Novo Nordisk Investigational Site
    Bucharest, 020475, Romania
  • Novo Nordisk Investigational Site
    Bucharest, 020992, Romania
  • Novo Nordisk Investigational Site
    Bucharest, Romania
  • Novo Nordisk Investigational Site
    Almería, 04001, Spain
  • Novo Nordisk Investigational Site
    Partida de Bacarot, 03114, Spain
  • Novo Nordisk Investigational Site
    Sevilla, 41010, Spain
  • Novo Nordisk Investigational Site
    Valencia, 46014, Spain
  • Novo Nordisk Investigational Site
    Valladolid, 47011, Spain
09

References and documents

Publications

  • Heise T, Tack CJ, Cuddihy R, Davidson J, Gouet D, Liebl A, Romero E, Mersebach H, Dykiel P, Jorde R. A new-generation ultra-long-acting basal insulin with a bolus boost compared with insulin glargine in insulin-naive people with type 2 diabetes: a randomized, controlled trial. Diabetes Care. 2011 Mar;34(3):669-74. doi: 10.2337/dc10-1905. Epub 2011 Feb 1. PubMed 21285389 ↗
  • Ma Z, Parkner T, Christiansen JS, Laursen T. IDegAsp: a novel soluble insulin analogs combination. Expert Opin Biol Ther. 2012 Nov;12(11):1533-40. doi: 10.1517/14712598.2012.722203. Epub 2012 Sep 4. PubMed 22946603 ↗
  • Liebl A, Davidson J, Mersebach H, Dykiel P, Tack CJ, Heise T. A novel insulin combination of insulin degludec and insulin aspart achieves a more stable overnight glucose profile than insulin glargine: results from continuous glucose monitoring in a proof-of-concept trial. J Diabetes Sci Technol. 2013 Sep 1;7(5):1328-36. doi: 10.1177/193229681300700524. PubMed 24124961 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 20, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00614055
Lead sponsor
Novo Nordisk A/S
Responsible party
Sponsor
First posted
Feb 13, 2008
Start date
Jan 2008
Primary completion
Jul 2008
Completion
Jul 2008
Results posted
Nov 17, 2015
Last update
Mar 20, 2017

Study contacts

Global Clinical Registry (GCR, 1452)
study director · Novo Nordisk A/S

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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