Clinical Trial Results:
A Multicenter, Open label, Non-comparative Study to Evaluate the Safety of Entocort EC for the Treatment of Crohn's Disease in Paediatric Subjects Aged 5 to 17 Years, Inclusive

Summary
EudraCT number	2011-003743-22
Trial protocol	DE   IT
Global end of trial date	10 Sep 2014
Results information
Results version number	v1(current)
This version publication date	01 Feb 2017
First version publication date	13 May 2015
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information Top of page
Trial identification
Sponsor protocol code	D9422C00001
Additional study identifiers
ISRCTN number	-
US NCT number	NCT01444092
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	AstraZeneca R&D Molndal
Sponsor organisation address	Pepparedsleden 1, Mölndal, Sweden, SE-431 83
Public contact	Tore Persson, AstraZeneca R&D Molndal, +46 31 7766069, tore.teb.persson@astrazeneca.com
Scientific contact	Stefan Eklund, AstraZeneca R&D Molndal, +46 31 7762557 , stefan.eklund@astrazeneca.com
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	Yes
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	26 Dec 2014
Is this the analysis of the primary completion data?	Yes
Primary completion date	10 Sep 2014
Global end of trial reached?	Yes
Global end of trial date	10 Sep 2014
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	The primary objective of this study was to investigate the safety of Entocort EC in a pediatric population treated for mild-to-moderate Crohn’s disease
Protection of trial subjects	None
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	03 Nov 2011
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	United States: 47
Country: Number of subjects enrolled	Canada: 19
Country: Number of subjects enrolled	Germany: 2
Country: Number of subjects enrolled	Italy: 15
Country: Number of subjects enrolled	Poland: 40
Worldwide total number of subjects	123
EEA total number of subjects	57
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	23
Adolescents (12-17 years)	100
Adults (18-64 years)	0
From 65 to 84 years	0
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	This study was to enroll approximately 110 subjects at study centers in the United States and at multiple centers throughout Europe and Canada.
Pre-assignment
Screening details	Eligibility for study enrollment will be assessed at the screening and enrollment visit (Visit 1). If appropriate, subjects will be enrolled into the study and begin to receive study medication at this visit. 123 subjects were screened and 108 were enrolled.
Period 1
Period 1 title	Enrollment/screening/start of treatment
Is this the baseline period?	Yes
Allocation method	Not applicable
Blinding used	Not blinded
Arms
Arm title	Entocort
Arm description	-
Arm type	Experimental
Investigational medicinal product name	Entocort EC
Investigational medicinal product code
Other name
Pharmaceutical forms	Capsule
Routes of administration	Oral use
Dosage and administration details	9 or 6 mg once daily in the morning
Number of subjects in period 1 [1] Entocort Started 108 Completed 108
Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Out of 123 enrolled patients under Trial information only 108 were treated. 15 patients were enrolled but not treated (did not meet the criteria for entering).
Period 2
Period 2 title	Overall study
Is this the baseline period?	No
Allocation method	Not applicable
Blinding used	Not blinded
Arms
Arm title	Entocort
Arm description	Entocort EC 9 or 6 mg/day
Arm type	Experimental
Investigational medicinal product name	Entocort EC
Investigational medicinal product code
Other name
Pharmaceutical forms	Capsule
Routes of administration	Oral use
Dosage and administration details	9 or 6 mg once daily in the morning
Number of subjects in period 2 Entocort Started 108 Completed 91 Not completed 17      Protocol deviation 1      Study-specific criterion 1      Lack of efficacy 6      Adverse event, non-fatal 8      Consent withdrawn by subject 1

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Entocort
Reporting group description	-
Reporting group values Entocort Total Number of subjects 108 108 Age categorical Units: Subjects     In utero 0 0     Preterm newborn infants (gestational age < 37 wks) 0 0     Newborns (0-27 days) 0 0     Infants and toddlers (28 days-23 months) 0 0     Children (2-11 years) 18 18     Adolescents (12-17 years) 90 90     Adults (18-64 years) 0 0     From 65-84 years 0 0     85 years and over 0 0 Age Continuous Units: Years     arithmetic mean (standard deviation) 13.7 ± 2.4 - Gender, Male/Female Units: Participants     Female 51 51     Male 57 57 Age, Customized Units: Subjects     =<8 Yrs 5 5     >8 Yrs 103 103 Race, Customized Units: Subjects     Asian 1 1     Black Or African American 4 4     Other 3 3     White 100 100

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Entocort
Reporting group description	-
Reporting group title	Entocort
Reporting group description	Entocort EC 9 or 6 mg/day

End points Top of page

Primary: Any adverse event Top of page
End point title	Any adverse event [1]
End point description
End point type	Primary
End point timeframe	12 weeks
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Detailed information about the adverse events is to be found in the Adverse events section.
End point values Entocort Number of subjects analysed 108 Units: Patients 79
No statistical analyses for this end point

Primary: Any adverse event Top of page

Secondary: PCDAI Top of page
End point title	PCDAI
End point description	Paediatric Crohn’s Disease Activity Index
End point type	Secondary
End point timeframe	8 weeks
End point values Entocort Number of subjects analysed 105 [2] Units: Score arithmetic mean (standard deviation)     Baseline (Day1) 19.1 ± 10.1     Change after 8 weeks -10 ± 10.1
Notes [2] - Full analysis set (all patients with a PCDAI after 8 weeks)
No statistical analyses for this end point

Secondary: PCDAI Top of page

Secondary: IMPACT 3 Top of page
End point title	IMPACT 3
End point description
End point type	Secondary
End point timeframe	8 weeks
End point values Entocort Number of subjects analysed 107 Units: Score arithmetic mean (standard deviation)     Baseline (Day 1) 132.1 ± 18.8     Change after 8 weeks 7.9 ± 13.3
No statistical analyses for this end point

Secondary: IMPACT 3 Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	12 weeks
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	17.0
Reporting groups
Reporting group title	Entocort
Reporting group description	Entocort™ EC 9/6/3 mg
Serious adverse events Entocort Total subjects affected by serious adverse events      subjects affected / exposed 8 / 108 (7.41%)      number of deaths (all causes) 0      number of deaths resulting from adverse events 0 Gastrointestinal disorders Crohn's disease      subjects affected / exposed 4 / 108 (3.70%)      occurrences causally related to treatment / all 0 / 4      deaths causally related to treatment / all 0 / 0 Diarrhoea haemorrhagic      subjects affected / exposed 1 / 108 (0.93%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Small intestinal obstruction      subjects affected / exposed 1 / 108 (0.93%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Skin and subcutaneous tissue disorders Erythema nodosum      subjects affected / exposed 1 / 108 (0.93%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Musculoskeletal and connective tissue disorders Musculoskeletal chest pain      subjects affected / exposed 1 / 108 (0.93%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Metabolism and nutrition disorders Hypokalaemia      subjects affected / exposed 1 / 108 (0.93%)      occurrences causally related to treatment / all 1 / 1      deaths causally related to treatment / all 0 / 0
Frequency threshold for reporting non-serious adverse events: 0%
Non-serious adverse events Entocort Total subjects affected by non serious adverse events      subjects affected / exposed 78 / 108 (72.22%) Vascular disorders Pallor      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 General disorders and administration site conditions Chest pain      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Influenza like illness      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Malaise      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Pyrexia      subjects affected / exposed 3 / 108 (2.78%)      occurrences all number 3 Tenderness      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Psychiatric disorders Affect lability      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Agitation      subjects affected / exposed 2 / 108 (1.85%)      occurrences all number 2 Anxiety      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Depression      subjects affected / exposed 2 / 108 (1.85%)      occurrences all number 2 Insomnia      subjects affected / exposed 6 / 108 (5.56%)      occurrences all number 6 Irritability      subjects affected / exposed 14 / 108 (12.96%)      occurrences all number 14 Sleep disorder      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Mood swings      subjects affected / exposed 3 / 108 (2.78%)      occurrences all number 3 Reproductive system and breast disorders Menstrual disorder      subjects affected / exposed 2 / 108 (1.85%)      occurrences all number 2 Dysmenorrhoea      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Metrorrhagia      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Injury, poisoning and procedural complications Concussion      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Incision site complication      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Contusion      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Procedural pain      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Investigations Activated partial thromboplastin time prolonged      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Blood albumin decreased      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Blood cortisol decreased      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Blood cortisol increased      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Haemoglobin decreased      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 C-reactive protein increased      subjects affected / exposed 2 / 108 (1.85%)      occurrences all number 2 Mean cell volume decreased      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Occult blood positive      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Protein urine present      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Red blood cell sedimentation rate increased      subjects affected / exposed 3 / 108 (2.78%)      occurrences all number 3 Urine output decreased      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Cardiac disorders Tachycardia      subjects affected / exposed 2 / 108 (1.85%)      occurrences all number 2 Respiratory, thoracic and mediastinal disorders Cough      subjects affected / exposed 3 / 108 (2.78%)      occurrences all number 3 Respiratory tract congestion      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Blood and lymphatic system disorders Anaemia      subjects affected / exposed 5 / 108 (4.63%)      occurrences all number 5 Increased tendency to bruise      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Lymphadenopathy      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Nervous system disorders Disturbance in attention      subjects affected / exposed 3 / 108 (2.78%)      occurrences all number 3 Dizziness      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Headache      subjects affected / exposed 9 / 108 (8.33%)      occurrences all number 9 Lethargy      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Memory impairment      subjects affected / exposed 4 / 108 (3.70%)      occurrences all number 4 Migraine      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Psychomotor hyperactivity      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Syncope      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Eye disorders Iritis      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Scleritis      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Gastrointestinal disorders Abdominal distension      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Abdominal pain      subjects affected / exposed 16 / 108 (14.81%)      occurrences all number 16 Abdominal mass      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Abdominal pain lower      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Abdominal tenderness      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Anal fissure      subjects affected / exposed 2 / 108 (1.85%)      occurrences all number 2 Anal haemorrhage      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Anal skin tags      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Breath odour      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Cheilosis      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Constipation      subjects affected / exposed 2 / 108 (1.85%)      occurrences all number 2 Crohn's disease      subjects affected / exposed 7 / 108 (6.48%)      occurrences all number 7 Diarrhoea      subjects affected / exposed 2 / 108 (1.85%)      occurrences all number 2 Dyspepsia      subjects affected / exposed 3 / 108 (2.78%)      occurrences all number 3 Enterocolitis      subjects affected / exposed 2 / 108 (1.85%)      occurrences all number 2 Haematochezia      subjects affected / exposed 3 / 108 (2.78%)      occurrences all number 3 Proctalgia      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Nausea      subjects affected / exposed 6 / 108 (5.56%)      occurrences all number 6 Rectal haemorrhage      subjects affected / exposed 2 / 108 (1.85%)      occurrences all number 2 Vomiting      subjects affected / exposed 5 / 108 (4.63%)      occurrences all number 5 Renal and urinary disorders Haematuria      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Skin and subcutaneous tissue disorders Alopecia      subjects affected / exposed 2 / 108 (1.85%)      occurrences all number 2 Acne      subjects affected / exposed 15 / 108 (13.89%)      occurrences all number 15 Dry skin      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Erythema nodosum      subjects affected / exposed 2 / 108 (1.85%)      occurrences all number 2 Hair growth abnormal      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Hirsutism      subjects affected / exposed 5 / 108 (4.63%)      occurrences all number 5 Lipohypertrophy      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Pruritus      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Rash      subjects affected / exposed 2 / 108 (1.85%)      occurrences all number 2 Skin striae      subjects affected / exposed 2 / 108 (1.85%)      occurrences all number 2 Musculoskeletal and connective tissue disorders Arthralgia      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Back pain      subjects affected / exposed 2 / 108 (1.85%)      occurrences all number 2 Fistula      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Musculoskeletal discomfort      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Musculoskeletal pain      subjects affected / exposed 2 / 108 (1.85%)      occurrences all number 2 Myalgia      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Osteoporosis      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Pain in extremity      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Endocrine disorders Cushingoid      subjects affected / exposed 13 / 108 (12.04%)      occurrences all number 13 Metabolism and nutrition disorders Decreased appetite      subjects affected / exposed 6 / 108 (5.56%)      occurrences all number 6 Dehydration      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Hyperamylasaemia      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Hyperphagia      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Increased appetite      subjects affected / exposed 17 / 108 (15.74%)      occurrences all number 17 Infections and infestations Acarodermatitis      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Conjunctivitis      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Enteritis infectious      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Gastroenteritis      subjects affected / exposed 2 / 108 (1.85%)      occurrences all number 2 Otitis externa      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Nasopharyngitis      subjects affected / exposed 4 / 108 (3.70%)      occurrences all number 4 Pharyngitis      subjects affected / exposed 4 / 108 (3.70%)      occurrences all number 4 Rhinitis      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Rectal abscess      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Tooth abscess      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Upper respiratory tract infection      subjects affected / exposed 3 / 108 (2.78%)      occurrences all number 3 Urinary tract infection      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Viral infection      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1 Viral pharyngitis      subjects affected / exposed 1 / 108 (0.93%)      occurrences all number 1

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? Yes
Date	Amendment
23 May 2013	The body weight cutoff for 9 mg or 6 mg/day was changed from 30 kg to 25 kg
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
None reported

More information Top of page