Clinical Trials Register

Summary
EudraCT Number:	2013-002819-10
Sponsor's Protocol Code Number:	M13-621
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-10-14
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2013-002819-10

A.3

Full title of the trial

A Double-blind, Randomized, Multicenter, Cross-over Study to Compare the Effect of Creon N and Creon® on Fat Digestion in Subjects ≥ 12 years of Age with Pancreatic Exocrine Insufficiency Due to Cystic Fibrosis

Kettős vak, randomizált, többcentrumos, keresztezett klinikai vizsgálat a Creon N és a Kreon zsíremésztésre gyakorolt hatásának összehasonlítására a cisztás fibrózis miatt kialakult exokrin hasnyálmirigy elégtelenségű 12 éves és ennél idősebb betegeken

A.3.1

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

A Creon N és a Kreon zsíremésztésre gyakorolt hatásának összehasonlítása a cisztás fibrózis miatt kialakult exokrin hasnyálmirigy elégtelenségű 12 éves és ennél idősebb betegeken

A.4.1

Sponsor's protocol code number

M13-621

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	Abbott Laboratories GmbH
B.1.3.4	Country	Germany
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	Abbott Laboratories GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Abbott Laboratories GmbH
B.5.2	Functional name of contact point	Senior Clinical Trial Manager
B.5.3	Address:
B.5.3.1	Street Address	Freundallee 9A
B.5.3.2	Town/ city	Hannover
B.5.3.3	Post code	30173
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49511 6750 2733
B.5.5	Fax number	+49511 6750 2464
B.5.6	E-mail	gregor.eibes@abbott.com

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	CREON N 25000
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	not applicable
D.3.9.1	CAS number	8049-47-6
D.3.9.2	Current sponsor code	CREON N
D.3.9.3	Other descriptive name	PANCREATIN
D.3.9.4	EV Substance Code	SUB12545MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU/kg international unit(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25000
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)	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.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	Creon 25000
D.2.1.1.2	Name of the Marketing Authorisation holder	Abbott Laboratories GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	not assigned
D.3.9.1	CAS number	8049-47-6
D.3.9.3	Other descriptive name	PANCREATIN
D.3.9.4	EV Substance Code	SUB12545MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25000
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)	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

Pancreatic exocrine Insufficiency due to Cystic Fibrosis

Cisztás fibrózis miatt kialakult exokrin hasnyálmirigy elégtelenség

E.1.1.1

Medical condition in easily understood language

maldigestion of diatery macronutients (pancreas not producing enough enzymes for digestion of fat, sugars and proteins) in Cystic Fibrosis

Tápanyag lebontási zavar (a hasnyálmirigy nem termel elég enzimet a zsír, cukor és fehérje lebontásához) cisztás fibrózisban

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

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

To assess the therapeutic equivalence of Creon N 25000 with Creon® 25000 on coefficient of fat absorption (CFA) in adolescent and adult subjects with pancreatic exocrine insufficiency (PEI) due to cystic fibrosis (CF).

A Creon N 25 000 és Kreon 25 000 terápiás egyenértékűségének zsírfelszívódási koefficiensre (CFA) gyakorolt hatásának összehasonlítása a cisztás fibrózis (CF) miatti exokrin hasnyálmirigy rendellenességben (PEI) szenvedő serdülőkön és felnőtteken.

E.2.2

Secondary objectives of the trial

To investigate the effect of Creon N 25000 and Creon® 25000 on coefficient of nitrogen absorption (CNA),on stool fat and clinical symptomatology (stool frequency, stool consistency, abdominal pain, flatulence).
Safety Objectives:
To evaluate the short-term safety of Creon N 25000 and Creon® 25000, including vital signs, body weight, physical examination, safety laboratory values, and adverse events (AEs).

A Creon N 25 000 és Kreon 25 000 hatásának vizsgálata a nitrogén felszívódási koefficiensre (CNA), a széklet zsírtartalmára és a klinikai tünetekre (székelés gyakorisága, széklet állaga, hasi fájdalom, puffadás).
A biztonságosság értékelése
A rövid ideig tartó Creon N 25 000 és Kreon 25 000 alkalmazás biztonságosságának értékelése a vitális jelek, testtömeg, fizikális vizsgálat, laborvizsgálat és nem várt események (AE) vonatkozásában.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed informed consent given by the subject, or the parents, or a legally acceptable representative. If required by the Institutional Review Board/Ethics Committee (IRB/IEC), assent will be given by the subject
2. Age ≥ 12 years
3. Subjects who are able to swallow capsules with each meal and snacks
4. Diagnosis of CF confirmed by two positive chloride sweat tests or gene analysis
5. Diagnosis of pancreatic exocrine insufficiency proven by:
a. CFA < 70% without supplementation
b. or
Human fecal elastase < 50 µg/g stool
6. Currently receiving treatment with a commercially available pancreatic enzyme product and on a continuous dose of this product for more than 3 months
7. Clinically stable condition without evidence of acute respiratory disease within 1 month of enrollment
8. Stable body weight defined as no more than a 5% decline within 3 months of enrolment
9. Females of child-bearing potential should agree to continue using a medically acceptable method of birth control throughout the study and for 30 days immediately after the last dose of study drug. Medically acceptable methods of birth control include bilateral tubal ligation or the use of either a contraceptive implant, a contraceptive injection (Depo-Provera™), an intrauterine device, or an oral contraceptive taken within the past 3 months where the subject agrees to continue using during the study or to adopt another birth control method, or a double-barrier method which consists of a combination of any two of the following: diaphragm, cervical cap, condom, or spermicide.

1. Önkéntes beleegyező nyilatkozat, amelyet a beteg, a szülő vagy a nyilatkozattételre jogosult aláír.
2. 12 éves vagy ennél idősebb életkor.
3. Olyan betegek, akik képesek minden fő és közbenső étkezéskor kapszulát lenyelni.
4. CF diagnózis, amelyet két pozitív verejtékvizsgálat (klorid-szint) vagy genetikai vizsgálat igazolt.
5. A hasnyálmirigy exokrin alulműködése, amelyet az alábbi igazol:
a. CFA <70%, kiegészítés nélkül,
b. vagy
Humán széklet elasztáz <50 µg/g széklet
6. Jelenleg is tartó kezelés több mint 3 hónapja, folyamatosan, azonos adagban, kereskedelmi forgalomban kapható hasnyálmirigy enzimet tartalmazó készítménnyel.
7. Klinikailag stabil állapot akut légúti betegség jele nélkül a bevonást megelőző 1 hónapon belül.
8. Stabil testsúly, azaz 3 hónapon belül 5%-nál nagyobb csökkenés nem következett be.
9. Fogamzó képes nőknek gyógyászatilag elfogadott módszerrel kell védekezniük a vizsgálat alatt és további 30 napig a vizsgálati készítmény utolsó bevétele után. Elfogadott módszernek minősül: kétoldali petevezeték-lekötés, fogamzásgátló implantátum vagy fogamzásgátló injekció (Depo-Provera™) alkalmazása, intrauterin eszköz, vagy per os fogamzásgátló szedése 3 hónapon belül. A vizsgálati személy beleegyezik ezek további alkalmazásába a vizsgálat alatt, vagy más fogamzásgátló módszert alkalmaz, vagy kettős barrier módszert, amely a következők közül kettőnek a kombinációja: filmfólia, pesszárium, kondom vagy spermicid.

E.4

Principal exclusion criteria

1. Evidence of cardiovascular, respiratory, urogenital, gastrointestinal/hepatic (except underlying disease), hematologic/immunologic, head, ears, eyes, nose, throat, dermatologic/connective tissue, musculoskeletal, metabolic/nutritional (except underlying disease), endocrine (except diabetes mellitus), neurologic/psychiatric, allergy, recent major surgery, or other relevant diseases as revealed by history, physical examination and/or laboratory assessments, which could limit participation in or completion of the study
2. History of acute abdomen
3. History of fibrosing colonopathy
4. History of distal intestinal obstruction syndrome (DIOS) within 6 months prior to enrollment
5. Solid organ transplant or surgery affecting the large bowel other than appendectomy
6. Small bowel surgery that significantly affected absorptive capacity (e.g. gastrectomy or pancreatectomy)
7. Pregnancy or lactation
8. Any type of malignancy involving the digestive tract in the last 5 years
9. Celiac disease or Crohn’s disease
10. Known allergy to pancreatin or inactive ingredients (excipients) of pancreatin capsules
11. Suspected non-compliance or non-cooperation
12. Intake of experimental drugs within 30 days prior to study start
13. Mental disability or any other lack of fitness, in the Investigator's opinion, to preclude subject’s participation in or ability to complete the study
14. Diagnosis of human immunodeficiency virus in medical history.

1. Szív-érrendszeri, légúti, urogenitális, gasztrointesztinális és májra terjedő (kivéve a fennálló betegséget), hematológiai/immunológiai, fej-, fül-, szem-, orr-, garat-, dermatológiai/kötőszöveti, váz-izomrendszeri, anyagcsere/táplálkozási (kivéve fennálló betegséget), endokrin/táplálkozási (kivéve diabetes mellitus), neurológiai/pszichiátriai, allergiás, közelmúltban jelentős műtét, vagy egyéb releváns betegség jelei, amelyek a kórtörténetből, a fizikális és/vagy laboratóriumi vizsgálatból derültek ki, és gátolhatják a vizsgálatban való részvételt vagy végigvitelét.
2. Akut has a kórtörténetben.
3. Fibrotizáló kolonopátia a kórtörténetben.
4. Distal intestinal obstruction syndrome (DIOS) a kórtörténetben, a beválasztást megelőző 6 hónapon belül.
5. Transzplantáció vagy a vastagbelet érintő műtét (kivéve appendectomia).
6. Vékonybél műtét, amely jelentősen befolyásolja a felszívódást (pl. gastrectomia vagy pancreatectomia).
7. Terhesség vagy szoptatás.
8. Bármilyen rosszindulatú betegség az elmúlt 5 évben, amely az emésztőrendszert érintette.
9. Coeliákia vagy Crohn-betegség.
10. Ismert allergia pankreatin-, vagy pankreatin-kapszulák összetevői iránt.
11. Együttműködés vagy kooperáció feltételezhető hiánya.
12. Vizsgálati készítmény szedése a bevonás előtti 30 napban.
13. Mentális vagy bármi más alkalmatlanság, amely a vizsgáló véleménye szerint meggátolja, hogy az egyén a vizsgálatot lefolytassa.
14. HIV-fertőzés diagnózisa a kórtörténetben.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy criterion is the CFA. CFA will be calculated from fat intake and fat excretion, according to the formula:
CFA (%) = 100 [fat intake – fat excretion] / fat intake

Hatásosság elsődleges változója a CFA. A CFA-t a bevitt zsír és a kiválasztott zsírból számolják a következő képlet szerint:
CFA (%) = 100 [zsírbevitel – kiválasztott zsír] / zsírbevitel

E.5.1.1

Timepoint(s) of evaluation of this end point

The CFA values will be compared between the Creon N 25000 and Creon® 25000 treatment periods.

Creon N 25000 és Kreon 25000 kezelési periódusok CFA értékeit hasonlítják össze.

E.5.2

Secondary end point(s)

The Secondary efficacy criteria are the coefficient of nitrogen absorption (CNA), stool fat and clinical symptomatology (stool frequency, stool consistency, abdominal pain, flatulence).
The safety data collected during the study are vital signs, physical examination, safety laboratory values and adverses events.

Másodlagos változók: CNA, széklet zsírtartalma, klinikai tünettan (székletürítés gyakorisága, széklet állaga, hasi fájdalom, puffadás). A biztonságosság értékelésekor a vitális jelek, testtömeg, fizikális vizsgálat, laborvizsgálat és nem várt események (AE) adatait kell figyelembe venni.

E.5.2.1

Timepoint(s) of evaluation of this end point

The values will be compared between the Creon N 25000 and Creon® 25000 treatment periods.
Safety parameters are assessed throughout the study.

Creon N 25000 és Kreon 25000 kezelési periódusok értékeit hasonlítják össze.
A biztonságosságot az egész vizsgálat során értékelik.

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

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

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)

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

Yes

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.8.2.4

Number of treatment arms in the trial

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

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

Russian Federation

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

LVLP

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 months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

For minor childs, the parents will have to give their consent.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

none

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-11-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-11-14

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-08-25

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IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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