Clinical Trials Register

Summary
EudraCT Number:	2014-004519-35
Sponsor's Protocol Code Number:	PANC2002
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2014-12-08
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

UK - MHRA

A.2

EudraCT number

2014-004519-35

A.3

Full title of the trial

A Phase II, Multicenter, Parallel-Group, Active-Controlled, Randomized, Double-blind, Dose-Ranging Study to Evaluate the Efficacy and Safety of Different Doses of Creon IR in Subjects with Pancreatic Exocrine Insufficiency due to Cystic Fibrosis

A.3.1

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

A.4.1

Sponsor's protocol code number

PANC2002

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 Healthcare Products BV
B.5.2	Functional name of contact point	Hanneke Van Assche
B.5.3	Address:
B.5.3.1	Street Address	C.J. van Houtenlaan 36
B.5.3.2	Town/ city	Weesp
B.5.3.3	Post code	1381 CP
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+3129447 7367
B.5.5	Fax number	+3129441 0571
B.5.6	E-mail	hanneke.vanassche@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 IR
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 IR
D.3.9.3	Other descriptive name	PANCREATIN (PAncreas Powder)
D.3.9.4	EV Substance Code	SUB12545MIG
D.3.10	Strength
D.3.10.1	Concentration unit	U unit(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	4000 to 30000
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	Kreon 25 000
D.2.1.1.2	Name of the Marketing Authorisation holder	Abbott Laboratories GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Czech Republic
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® 25,000
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 (Pancreas Powder)
D.3.9.4	EV Substance Code	SUB12545MIG
D.3.10	Strength
D.3.10.1	Concentration unit	U 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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

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

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

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 compare and model the efficacy of four different doses of Creon Immediate Release (IR) and the active control (Creon® (Delayed Release/Gastro-Resistant) [Creon® DR/GR]) in subjects with pancreatic exocrine insufficiency (PEI) due to cystic fibrosis (CF). The primary efficacy objective is based on the evaluation of fat digestion as measured by coefficient of fat absorption (CFA) (%).

E.2.2

Secondary objectives of the trial

The secondary efficacy objective is to compare protein digestion (measured by coefficient of nitrogen absorption [CNA]), stool fat content and stool weight, of four different doses of Creon IR and Creon® (DR/GR) in subjects with PEI due to CF.

The safety objective is to determine the clinical safety of Creon IR based on the evaluation of clinical symptomatology associated with PEI (stool frequency, stool consistency, abdominal pain, flatulence), vital signs, physical examination findings, safety laboratory values and adverse events (AEs) in subjects with PEI due to CF.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subject has voluntarily signed and dated the ICF. For subjects aged less than 18 years, the parents, or a legally acceptable representative, must sign consent and, as required by the IEC, assent will be given by the subject.
2. Subject is 12 years old or older at the time of consent signature.
3. Subject has a diagnosis of CF previously confirmed by:
- a sweat chloride test > or equal to 60 mmol/Ls and/or
- two CF causing CFTR mutations and
- CF clinical features7,8.
4. Subject has a documented clinically confirmed diagnosis of pancreatic exocrine insufficiency.
5. Subject has human fecal elastase < 100 µg/g stool at screening.
6. Subject has PEI that is currently clinically controlled (no clinically overt steatorrhea or diarrhea) under treatment with a commercially available PERT, on an individually established dose regimen for more than 3 months, with a daily dose not exceeding 10,000 U lipase/kg/day.
7. Females of child-bearing potential should agree to continue using a medically acceptable method of birth control throughout the study and for 7 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 (e.g., Depo Provera™), an intrauterine device, or an oral contraceptive taken continually within the past three months and which 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

E.4

Principal exclusion criteria

1. Subject is < 18 years of age and has a Body Mass Index (BMI) Z-Score below -1.59 (minus 1.5).
2. Subject has a history of any of the following gastrointestinal disorders:
a. pancreatitis within 6 months prior to study entry;
b. fibrosing colonopathy;
c. distal ileal obstruction syndrome (DIOS) within 6 months prior to study entry;
d. celiac disease;
e. gastric bypass or partial/total gastrectomy;
f. Crohn’s disease;
g. small bowel surgery (other than minor resection due to meconium ileus without resulting in malabsorption syndrome).
h. Any type of malignancy involving the digestive tract in the last 5 years
3. Subjects with diabetes mellitus, for which the study specific dietary requirements may not be appropriate (See Section 8.1.1).
4. Subject has a history of other endocrine or respiratory (except mild asthma) medical illness non-related to CF, which might limit participation in or completion of the study.
5. Subject has a history of any clinically significant neurological, cardiac, renal, hepatic (including Hepatitis B or C), hematologic or psychiatric disease or disorder, or any other uncontrolled medical illness (except cystic fibrosis) which might limit participation in or completion of the study.
6. Subjects requiring concomitant treatment with any medication not allowed by the protocol or is expected to be needed.
7. Subjects requiring Naso-gastric, G-tubes or J-tubes.
8. Subject is currently participating in any other interventional clinical study or has taken any experimental drug within 30 days prior to Screening.
9. Subject is known to be HIV-positive.
10. Subject has a history of allergic reaction or significant sensitivity to pancreatin or inactive ingredients (excipients) of Creon® (DR/GR) or Creon IR

E.5 End points

E.5.1

Primary end point(s)

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

E.5.1.1

Timepoint(s) of evaluation of this end point

The values at the end of the double-blind treatment period of the four different doses of Creon IR, and of the active control Creon®,will be compared .

E.5.2

Secondary end point(s)

Secondary efficacy criteria are the CNA (Coefficient of Nitrogen Absorption), stool fat content, and stool weight.
CNA will be calculated from nitrogen intake and nitrogen according to the formula:
CNA (%) = 100 [nitrogen intake – nitrogen excretion] / nitrogen intake.

The safety data collected during the study are vital signs, physical
examination, safety laboratory values and adverses events.

E.5.2.1

Timepoint(s) of evaluation of this end point

The values at the end of the double-blind treatment period of the four different doses of Creon IR, and of the active control Creon®, will be compared .

Safety parameters are assessed throughout the study.

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

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

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.8.2.4

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

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

LVLS

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

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)

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

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)

The patient will return to original PERT therapy.

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

2014-12-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-02-23

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2015-05-19

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