Clinical Trials Register

Summary
EudraCT Number:	2009-011271-78
Sponsor's Protocol Code Number:	NN5401-3590
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-07-29
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2009-011271-78

A.3

Full title of the trial

A trial comparing efficacy and safety of NN5401 with insulin glargine in insulin naive subjects with type 2 diabetes

Ensayo para comparar la eficacia y seguridad de NN5401 frente a insulina glargina en sujetos con Diabetes tipo 2 sin tratamiento previo con insulina

A.4.1

Sponsor's protocol code number

NN5401-3590

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novo Nordisk A/S
B.1.3.4	Country	Denmark
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	SIAC
D.3.2	Product code	NN5401
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	844439-96-9
D.3.9.2	Current sponsor code	NNC 0100-0000-0454
D.3.9.3	Other descriptive name	insulin 454
D.3.10	Strength
D.3.10.1	Concentration unit	nmol/ml nanomole(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	420
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	116094-23-6
D.3.9.3	Other descriptive name	insulin aspart
D.3.10	Strength
D.3.10.1	Concentration unit	nmol/ml nanomole(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	180
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Lantus®
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi-Aventis Deutschland GmbH, D-65926 Frankfurt am Main, Germany
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	160337-95-1
D.3.9.3	Other descriptive name	insulin glargine
D.3.10	Strength
D.3.10.1	Concentration unit	U/ml unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

type 2 diabetes

Diabetes tipo 2

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.0
E.1.2	Level	LLT
E.1.2	Classification code	10045242
E.1.2	Term	Type II diabetes mellitus

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To confirm the efficacy of SIAC OD + metformin in controlling glycaemia with respect to change from baseline
in HbA1c after 26 weeks of treatment. This is done by comparing the difference in change from baseline in
HbA1c after 26 weeks of treatment between SIAC OD + metformin and insulin glargine OD + metformin to a
non-inferiory limit of 0.4%, and if non-inferiority is confirmed to a superiority limit of 0%.

E.2.2

Secondary objectives of the trial

To confirm superiority of SIAC OD + metformin over insulin glargine OD + metformin after 26 weeks of
treatment in terms of:
• Prandial plasma glucose (PG) increment at breakfast
• Fluctuation in nocturnal interstitial glucose (IG)
• Frequency of responders for HbA1c (<7.0%) without hypoglycaemic episodes
• Nocturnal hypoglycaemic episodes
• Body weight
To compare efficacy and safety after 26 weeks of treatment in terms of:
• Fasting plasma glucose (FPG) from central laboratory
• 9-point self measured plasma glucose (SMPG) profile
• Self measured plasma glucose for dose adjustments
• Glucose profile as measured with CGM in a sub-population
• Frequency of responders for HbA1c
• Frequency of responders for HbA1c without hypoglycaemic episodes
• Clinical and laboratory assessments
• â-cell function
• Cardiovascular risk (CV) markers
• Adverse events (AEs)
• Hypoglycaemic episodes
• Insulin dose
• Insulin antibodies
• Patient reported outcome (PRO)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Informed consent obtained before any trial-related activities. (Trial related activities are defined as any
procedure that would not have been performed during standard management of the subject)
2. Male or female ≥ 18 years of age
3. Type 2 diabetes mellitus (diagnosed clinically) for ≥ 6 months
4. HbA1c 7.5-11.0% (both inclusive) by central laboratory analysis
5. BMI ≤ 40.0 kg/m2
6. Insulin naive subject (Allowed are: Previous short term insulin treatment up to 14 days; Treatment during
hospitalisation or during gestational diabetes is allowed for periods longer than 14 days)
7. Ongoing treatment with: Metformin and at least one other OAD for at least 3 months prior to randomisation
with the minimum doses stated:
− Metformin:(including fixed combination products) 1500 mg or maximum tolerated dose (at least 1000 mg
daily)
− Insulin secretagogue (sulfonylurea or glinide): Minimum half of the daily maximal dose according to approved
labelling
− DPP-4 inhibitor: Minimum 100 mg daily or according to approved labelling
− Acarbose: minimum half of the daily maximal dose or maximum tolerated dose
8. Ability and willingness to adhere to the protocol including performance of SMPG profiles according to the
protocol
9. Subject is likely to comply with the Investigator’s instruction

E.4

Principal exclusion criteria

1. Anticipated change in concomitant medication known to interfere with glucose metabolism, such as systemic
corticosteroids, beta-blockers, MAO inhibitors
2. Off-label use of any concomitant medication, including OADs to be continued in the trial
3. Use within the last 3 months prior to Visit 1 of GLP-1 receptor agonists and/or
thiazolidinediones (TZDs)
4. Anticipated significant lifestyle change during the trial, e.g. shift work (including permanent night/evening
shift workers), as well as highly variable eating habits
5. Cardiovascular disease, within the last 6 months prior to visit 1, defined as: stroke; decompensated heart
failure New York Heart Association (NYHA)1 class III or IV; myocardial infarction; unstable angina pectoris; or
coronary arterial bypass graft or angioplasty.
6. Uncontrolled treated/untreated severe hypertension (systolic blood pressure ≥180 mm Hg and/or diastolic
blood pressure ≥ 100 mmHg)
7. Impaired liver function, defined as ALAT ≥ 2.5 times upper limit of normal (one retest analysed at the central
laboratory within a week of receipt or the result is permitted with the result of the last sample being conclusive)
8. Impaired renal function defined as serum-creatinine ≥ 125 μmol/L (≥ 1.4 mg/dL) for males and ≥ 110 μmol/
L (≥ 1.3 mg/dL) for females or glomerular filtration rate below 60 mL/min, calculated by the Cockroft & Gault
formula and according to local practise for metformin use (one retest analysed at the central laboratory within a
week is permitted with the result of the last sample being conclusive)
9. Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event during last 12 months) or
hypoglycaemic unawareness as judged by the Investigator or hospitalisation for diabetic ketoacidosis during the
previous 6 months
10. Proliferative retinopathy or maculopathy requiring treatment according to the Investigator
11. Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures
according to local requirements
12. Cancer and medical history (except basal cell skin cancer or squamous cell skin cancer)
13. Any clinically significant disease or disorder, except for conditions associated with type 2 diabetes, which in
the Investigator’s opinion could interfere with the results of the trial
14. Mental incapacity, psychiatric disorder, unwillingness or language barriers precluding adequate understanding
or co-operation, including subjects not able to read or write
15. Previous participation in this trial. Participation is defined as randomised. Re-screening of screening failures
is allowed only once within the limits of the recruitment period
16. Known or suspected allergy to any of the trial products or related products
17. Receipt of any investigational drug within one month prior Visit 1
18. Donation of blood or participation in other trials within one month prior to Visit 1
19. Known or suspected abuse of alcohol, narcotics or illicit drugs

E.5 End points

E.5.1

Primary end point(s)

Change from baseline in HbA1c after 26 weeks of treatment (analysed by central laboratory)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

Information not present in EudraCT

E.7.1.2

Bioequivalence study

Information not present in EudraCT

E.7.1.3

Other

Information not present in EudraCT

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	Information not present in EudraCT
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	Information not present in EudraCT
F.1.1.3	Newborns (0-27 days)	Information not present in EudraCT
F.1.1.4	Infants and toddlers (28 days-23 months)	Information not present in EudraCT
F.1.1.5	Children (2-11years)	Information not present in EudraCT
F.1.1.6	Adolescents (12-17 years)	Information not present in EudraCT
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2009-07-29.	Yes
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	62
F.4.2	For a multinational trial
F.4.2.1	In the EEA	221
F.4.2.2	In the whole clinical trial	752

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2009-10-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-10-09

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2010-10-26

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