ICH GCP - EU Clinical trials Registry - 2013-000356-18 (NL)

Kliniska prövningar Nct sida

Summary
EudraCT Number:	2013-000356-18
Sponsor's Protocol Code Number:	25051974
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-01-09
Trial 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

A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2013-000356-18

A.3

Full title of the trial

Effect of repeated intranasal cobalamin administration on cobalamin deficiency in elderly

Effect van herhaalde intranasale toediening van cobalamine op de cobalamine deficientie bij ouderen.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Effect of intranasal therapy for vitamin B12 deficiency

Het effect van intranale therapie bij vitamine B12 deficientie

A.3.2

Name or abbreviated title of the trial where available

ERICA

A.4.1

Sponsor's protocol code number

25051974

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Stichting Apotheek der Haarlemse Ziekenhuizen
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Stichting Apotheek der Haarlemse Ziekenhuizen
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Stichting Apotheek der Haarlemse Ziekenhuizen
B.5.2	Functional name of contact point	Monique Tillemans
B.5.3	Address:
B.5.3.1	Street Address	Boerhaavelaan 24
B.5.3.2	Town/ city	Haarlem
B.5.3.3	Post code	2035RC
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	0031235464054
B.5.5	Fax number	0031235464028
B.5.6	E-mail	mtillemans@sahz.nl

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	Cyanocobalamin, nasal spray 500 microgram/spray
D.3.4	Pharmaceutical form	Nasal spray, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intranasal use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CYANOCOBALAMIN
D.3.9.1	CAS number	68-19-9
D.3.9.3	Other descriptive name	CYANOCOBALAMIN
D.3.9.4	EV Substance Code	SUB06837MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5495
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
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	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
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	No
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

Cobalamin (vitamin B12) deficiency

Cobalamine (vitamine B12) deficientie

E.1.1.1

Medical condition in easily understood language

Vitamin B12 deficiency

Vitamine B12 tekort

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

In this study we investigate the effects of two intranasal cobalamin dosing regimens i.e. 1000 microgram administered once every three days and 1000 microgram administered once every day for two weeks, followed by once every week in elderly cobalamin deficient subjects on total transcobalamin and holotranscobalamin concentration.

The objective of this study is to establish the optimal intranasal cobalamin dosing regimen in elderly.

In deze studie wordt het effect van twee intranasale cobalamine doseerregimes; 1000 microgram elke 3 dagen toegediend en 1000 microgram elke dag toegediend gedurende twee weken, gevolgd door 1000 microgram elke week bij cobalamine deficiente ouderen op de transcobalamine en holotranscobalamine serum concentraties met elkaar vergeleken.
Het doel van dit onderzoek is om het optimale intranasale doseerregime bij ouderen vast te stellen.

E.2.2

Secondary objectives of the trial

Not applicable

Niet van toepassing

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- 65 years of age or over
- Total cobalamin serum level less than 250 pmol/l
- Suspect for cobalamin deficiency; hyperhomocysteinemia (> 15 micromoles/l) and/or 2 or more symptoms of cobalamin deficiency e.g. fatigue, memory impairment, irritability, personality changes, muscle weakness, depression, poor appetite, weight loss
- Capable of understanding the study information
- Informed consent

- 65 jaar of ouder
- Cobalamineconcentratie in serum kleiner dan 250 pmol/l
- Aanwijzigingen voor cobalamine deficientie; hyperhomocysteinemie (> 15 micromol/l) en/of twee of meer symptomen van cobalamine deficientie zoals moeheid, geheugenstoornissen, geirriteerdheid, gedragsveranderingen, spierzwakheid, depressie, verminderde eetlust, gewichtsverlies
- In staat om de studieinformatie te begrijpen
- Informed consent

E.4

Principal exclusion criteria

- Concomitant use intranasally administered medication
- Chronic rhinitis
- Use of cobalamin containing dietary supplements
- Severe Renal impairment i.e. MDRD less than 20 ml/min

- Gelijktijdig gebruik van andere nasaal toegediende medicatie
- Chronische rhinitis
- Gebruik van cobalamine bevattende voedingssupplementen
- Nierinsufficientie MDRD klaring kleiner dan 20 ml/min

E.5 End points

E.5.1

Primary end point(s)

Change in total transcobalamin and holotranscobalamin (holoTC) serum concentrations over time.

Verandering in totale transcobalamine en holotranscobalamine (holoTC) serumconcentraties in de tijd.

E.5.1.1

Timepoint(s) of evaluation of this end point

Total transcobalamin and holotranscobalamin serum concentrations will be established at t = 11, 7, 14, 30, 60 and 90 days.

Totale transcobalamine en holotranscobalamine serum concentraties worden bepaald op t = 1, 7, 14, 30, 60 en 90 dagen.

E.5.2

Secondary end point(s)

Changes in methylmalonic acid (MMA) and homocysteïne (tHcy) serum concentrations and changes in Geriatric Depression Scale (GDS) 5 and Mini Mental State Examination (MMSE) scores over time.

Veranderingen in methylmalonzuur en homocysteine serumconcentraties en veranderingen in de GDS (5) en MMSE scores in de tijd.

E.5.2.1

Timepoint(s) of evaluation of this end point

Methylmalonicacid and homocysteine serumconctrations will be evaluted at t = 1, 14 and 90 days
GDS and MMSE scores will be evaluated at t = 1 and 90 days

methylmalonzuur en homocysteine serumconcentraties worden bepaald op dag 1, 14 en 90.
De GDS en MMSE scores zullen op dag 1 en 90 worden bepaald.

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

Yes

E.6.4

Safety

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

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

zelfde product maar met een ander doseerregime

same medicinal product but different dosing regimen

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

The last visit of the last subject undergoing the trial.

Het laatste bezoek van de laatste patient in het onderzoek.

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

In case the patient still needs treatment for cobalamin deficiency, the patient will receive the standard care for cobalamin deficiency.

Wanneer een patient na de studie nog (onderhouds) behandeling nodig heeft voor de cobalamine deficientie, zal de patient de standaard behandeling voor cobalamine deficientie krijgen.

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

2023-12-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-12-23

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-03-17

Kliniska prövningar Nct sida

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