DiabetesPhase 2NCT00614055

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

A Phase 2 study testing insulin degludec/insulin aspart, insulin glargine and metformin in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 28 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Diabetes, Diabetes Mellitus, Type 2
What is being tested?: insulin degludec/insulin aspart, insulin glargine and metformin
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 178 participants
Where: 28 sitesin 5 countries
Study dates: Jan 2008to Jul 2008
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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)

Who cannot join

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

Trial locations and contacts

28 sites in 5 countries.

Country

City, postcode or hospital

28 sites in 5 countries

France6 sites

Novo Nordisk Investigational Site
Alès, 30100
Novo Nordisk Investigational Site
Brest, 29609
Novo Nordisk Investigational Site
La Rochelle, 17019
Novo Nordisk Investigational Site
Le Creusot, 71200
Novo Nordisk Investigational Site
Mont-de-Marsan, 40024
Novo Nordisk Investigational Site
Vénissieux, 69200

Other trials in France

Germany6 sites

Novo Nordisk Investigational Site
Bad Kreuznach, 55545
Novo Nordisk Investigational Site
Bad Mergentheim, 97980
Novo Nordisk Investigational Site
Dormagen, 41539
Novo Nordisk Investigational Site
Hohenmölsen, 06679
Novo Nordisk Investigational Site
Neuss, 41460
Novo Nordisk Investigational Site
Neuwied, 56564

Other trials in Germany

Norway6 sites

Novo Nordisk Investigational Site
Elverum, 2408
Novo Nordisk Investigational Site
Hamar, 2317
Novo Nordisk Investigational Site
Kongsvinger, 2212
Novo Nordisk Investigational Site
Oslo, 0586
Novo Nordisk Investigational Site
Stavanger, 4011
Novo Nordisk Investigational Site
Tromsø, 9038

Other trials in Norway

Romania5 sites

Novo Nordisk Investigational Site
Bucharest, 011234
Novo Nordisk Investigational Site
Bucharest, 020042
Novo Nordisk Investigational Site
Bucharest, 020475
Novo Nordisk Investigational Site
Bucharest, 020992
Novo Nordisk Investigational Site
Bucharest

Other trials in Romania

Spain5 sites

Novo Nordisk Investigational Site
Almería, 04001
Novo Nordisk Investigational Site
Partida de Bacarot, 03114
Novo Nordisk Investigational Site
Seville, 41010
Novo Nordisk Investigational Site
Valencia, 46014
Novo Nordisk Investigational Site
Valladolid, 47011

Other trials in Spain

About this study

Official title: A 16 Week Randomised, Open Labelled, 3 Armed, Parallel Group, Treat-to-target Trial Comparing Once Daily Injection of SIAC 30 (B), SIAC 45 (B) and Insulin Glargine, All in Combination With Metformin in Subjects With Type 2 Diabetes Failing on OAD Treatment

Conditions: Diabetes, Diabetes Mellitus, Type 2
Being tested: insulin degludec/insulin aspart, insulin glargine, metformin
Medical subject headings: Diabetes Mellitus, Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

insulin degludec/insulin aspartDrug
Formulation 1: Treat-to-target dose titration scheme, injection s.c., once daily
insulin degludec/insulin aspartDrug
Formulation 2: Treat-to-target dose titration scheme, injection s.c., once daily
insulin glargineDrug
Treat-to-target dose titration scheme, injection s.c., once daily
metforminDrug
Tablets, 1500-2000 mg/day

Study groups in NCT00614055
Study group	Role	What they receive
Insulin glargine	Active comparator	Not described Receives: Drug: insulin glargine; Drug: metformin
SIAC 30 (B)	Experimental	Not described Receives: Drug: insulin degludec/insulin aspart; Drug: metformin
SIAC 45 (B)	Experimental	Not described Receives: Drug: insulin degludec/insulin aspart; Drug: metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Glycosylated Haemoglobin (HbA1c)
Change from baseline in HbA1c after 16 weeks of treatment
Measured: Week 0, Week 16

Secondary outcomes (12)

Change in Fasting Plasma Glucose (FPG)
Change from baseline in FPG after 16 weeks of treatment
Measured: Week 0, Week 16
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.
Measured: Week 16
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.
Measured: Week 0 to Week 16 + 5 days follow up
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.
Measured: 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 06:00 (excluded).
Measured: Week 0 to Week 16 + 5 days follow up
Laboratory Safety Parameters (Biochemistry): Alanine Aminotransferase (ALAT)
Values at screening (Week -4) and at Week 16
Measured: Week -4, Week 16
Laboratory Safety Parameters (Biochemistry): Aspartate Aminotransferase (ASAT)
Values at screening (Week -4) and at Week 16
Measured: Week -4, Week 16
Laboratory Safety Parameters (Biochemistry): Serum Creatinine
Values at screening (Week -4) and at Week 16
Measured: Week -4, Week 16
Vital Signs: Diastolic Blood Pressure (BP)
Values at baseline (Week 0) and at Week 16
Measured: Week 0, Week 16
Vital Signs: Systolic Blood Pressure (BP)
Values at baseline (Week 0) and at Week 16
Measured: Week 0, Week 16
Vital Signs: Pulse
Values at baseline (Week 0) and at Week 16
Measured: Week 0, Week 16
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.
Measured: Week 0, Week 8, Week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2008Jul 2008

First posted13 Feb 2008 (estimated)
Study startJan 2008
Primary completionJul 2008
Study completionJul 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for DiabetesStudies of the same condition, open and under way.
More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 178 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00614055
Sponsor's protocol ID: NN5401-1791
Other IDs: 2007-002476-33
Status last verified: Feb 2017
First submitted: 30 Jan 2008
Last updated: 20 Mar 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 20 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A 16 Week Randomised, Open Labelled, 3 Armed, Parallel Group, Treat-to-target Trial Comparing Once Daily Injection of SIAC 30 (B), SIAC 45 (B) and Insulin Glargine, All in Combination With Metformin in Subjects With Type 2 Diabetes Failing on OAD Treatment
ClinicalTrials.gov ID: NCT00614055
Acronym / sponsor ID: NN5401-1791
Conditions: Diabetes, Diabetes Mellitus, Type 2
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 178 participants (actual)
Lead sponsor: Novo Nordisk A/SIndustry (pharma, biotech, devices)
Study start: Jan 2008
Primary completion: Jul 2008 (actual)
Study completion: Jul 2008 (actual)
First posted: 13 Feb 2008 (estimated)
Results: Posted 17 Nov 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Insulin glargine	Active comparator	Drug: insulin glargine, Drug: metformin
SIAC 30 (B)	Experimental	Drug: insulin degludec/insulin aspart, Drug: metformin
SIAC 45 (B)	Experimental	Drug: insulin degludec/insulin aspart, Drug: metformin

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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)

Key exclusion criteria (4 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
insulin degludec/insulin aspartFormulation 1: Treat-to-target dose titration scheme, injection s.c., once daily	Drug	SIAC 30 (B)
insulin degludec/insulin aspartFormulation 2: Treat-to-target dose titration scheme, injection s.c., once daily	Drug	SIAC 45 (B)
insulin glargineTreat-to-target dose titration scheme, injection s.c., once daily	Drug	Insulin glargine
metforminTablets, 1500-2000 mg/day	Drug	Insulin glargine, SIAC 30 (B), SIAC 45 (B)

Primary outcome

Change in Glycosylated Haemoglobin (HbA1c)
Time frame: Week 0, Week 16
Change from baseline in HbA1c after 16 weeks of treatment

12 secondary outcomes

Change in Fasting Plasma Glucose (FPG)
Time frame: Week 0, Week 16
Mean of 9-point Self Measured Plasma Glucose Profile (SMPG)
Time frame: Week 16
Rate of Treatment Emergent Adverse Events (AEs)
Time frame: Week 0 to Week 16 + 5 days follow up
Rate of Major and Minor Hypoglycaemic Episodes
Time frame: Week 0 to Week 16 + 5 days follow up
Rate of Nocturnal Major and Minor Hypoglycaemic Episodes
Time frame: Week 0 to Week 16 + 5 days follow up
Laboratory Safety Parameters (Biochemistry): Alanine Aminotransferase (ALAT)
Time frame: Week -4, Week 16
Laboratory Safety Parameters (Biochemistry): Aspartate Aminotransferase (ASAT)
Time frame: Week -4, Week 16
Laboratory Safety Parameters (Biochemistry): Serum Creatinine
Time frame: Week -4, Week 16
Vital Signs: Diastolic Blood Pressure (BP)
Time frame: Week 0, Week 16
Vital Signs: Systolic Blood Pressure (BP)
Time frame: Week 0, Week 16
Vital Signs: Pulse
Time frame: Week 0, Week 16
Physical Examination
Time frame: Week 0, Week 8, Week 16

Results and safety

Results posted to the registry on 17 Nov 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
SIAC 30 (B)	59	55
SIAC 45 (B)	59	53
Insulin Glargine	60	55

Primary outcome: Change in Glycosylated Haemoglobin (HbA1c)

Time frame: Week 0, Week 16. Mean (Standard Deviation). Unit: percentage of glycosylated haemoglobin

Measure	SIAC 30 (B) n = 59	SIAC 45 (B) n = 59	Insulin Glargine n = 60
Value	-1.31 (1.01)	-1.46 (1.39)	-1.29 (1.10)

Population analysed: Full analysis set (FAS) included all randomised subjects and missing data was imputed using last observation carried forward (LOCF).

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: The adverse events were collected in a time frame of 16 weeks + 7 days follow up. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
SIAC 30 (B)	2 of 59 (3.4%)	23 of 59 (39%)	Not reported
SIAC 45 (B)	1 of 59 (1.7%)	16 of 59 (27.1%)	Not reported
Insulin Glargine	0 of 60 (0%)	13 of 60 (21.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 21285389Heise 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.
Results publication: PubMed 22946603Ma 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.
Results publication: PubMed 24124961Liebl 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.
Clinical Trials at Novo NordiskLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Global Clinical Registry (GCR, 1452) study director

Novo Nordisk A/S

28 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing insulin degludec/insulin aspart, insulin glargine and metformin in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 28 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in France, Germany, Norway, Romania, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Nov 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Glycosylated Haemoglobin (HbA1c) (time frame: Week 0, Week 16). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00614055, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2017.