Clinical Trials Register

Summary
EudraCT Number:	2011-005161-20
Sponsor's Protocol Code Number:	SCC01
National Competent Authority:	Ireland - HPRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-12-05
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Ireland - HPRA

A.2

EudraCT number

2011-005161-20

A.3

Full title of the trial

A Randomised Controlled Double-Blind Trial of Intranasal Fentanyl versus Intravenous Morphine in the Emergency Department Treatment of Severe Painful Sickle Cell Crises in Children

A.3.1

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

Sickle cell anaemia is an inherited blood disorder which results in abnormal sickle shaped red blood cells which do not fit well through small blood vessels. These blockages prevent oxygen (in blood) from reaching different parts of the body resulting in painful crisis. This study will compare the effectiveness of two types of pain medication, one given through a vein and one squirted up the nose.

A.4.1

Sponsor's protocol code number

SCC01

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	University College Dublin Clinical Research Centre
B.1.3.4	Country	Ireland
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	The National Children's Research Centre, Our Lady's Children's Hospital, Crumlin
B.4.2	Country	Ireland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Our Lady's Children's Hospital, Crumlin
B.5.2	Functional name of contact point	Dr Michael Barrett
B.5.3	Address:
B.5.3.1	Street Address	Our Lady's Children's Hospital, Crumlin
B.5.3.2	Town/ city	Dublin
B.5.3.3	Post code	Dublin 12
B.5.3.4	Country	Ireland
B.5.4	Telephone number	353014096814

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	Yes
D.2.1.1.1	Trade name	Morphine Sulphate Injection BP
D.2.1.1.2	Name of the Marketing Authorisation holder	Antigen Pharmaceuticals Ltd, Roscrea, County Tipperary
D.2.1.2	Country which granted the Marketing Authorisation	Ireland
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	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	64-31-3
D.3.9.3	Other descriptive name	MORPHINE SULPHATE
D.3.9.4	EV Substance Code	SUB12162MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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.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	Sublimaze
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag Ltd 50-100 Holmers Farm Way, High Wycombe, Bucks, HP12 4EG, UK
D.2.1.2	Country which granted the Marketing Authorisation	Ireland
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	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	FENTANYL CITRATE
D.3.9.1	CAS number	990-73-8
D.3.9.4	EV Substance Code	SUB02129MIG
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	50
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	Yes
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	Solution for injection
D.8.4	Route of administration of the placebo	Intravenous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Intranasal use (Noncurrent)

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Severe Painful Sickle Cell Disease Crises in Children

E.1.1.1

Medical condition in easily understood language

Sickle cell anaemia is an inherited blood disorder which results in abnormal sickle shaped red blood cells which do not fit well through small blood vessels.

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10040644
E.1.2	Term	Sickle cell disease
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to illustrate the comparative efficacy of intranasal fentanyl to IV morphine in reducing severe pain associated with Painful Sickle Cell Crises in the Emergency Department.

E.2.2

Secondary objectives of the trial

The secondary objectives of this study include:
Assessment of the time to analgesic effect;
Assessent of the need for rescue analgesia, defined as exacerbation of pain requiring supplemental analgesia;
Assessment of other secondary effects including:
o Nausea and vomiting
o Respiratory depression
o Cardiovascular depression
o Sedation level

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion – Screening
Ages 1 – 21 years;
≥10kg and ≤70kg;
Known sickle cell disease with risk of or a history of painful crisis;
Willing to verbally re-consent during the next period of painful crisis.

Inclusion Criteria - Randomisation:
Ages 1 – 21 years;
≥10kg and ≤70kg;
Known sickle cell disease presenting with severe pain;
Written informed consent, ideally from both parents (and assent, where appropriate), obtained prior to painful crisis;
Verbal consent (and assent, where appropriate) obtained at the time of the painful crisis;
Hospital admission required for painful crisis.

E.4

Principal exclusion criteria

Exclusion Criteria – Screening
Previous enrolment into the trial;
Patient has a history of allergic reaction to morphine or fentanyl;
Patient receiving or requiring drug-dependency therapy;
Contraindications to fentanyl usage which include:
o Use in patients with hypersensitivity or idiosyncratic response to the active ingredient;
o Use in patients with respiratory depression, cyanosis, excessive bronchial exudation, asthma attack, or chronic pulmonary disease;
o Use in patients after operative interventions in the biliary tract;
o Use in patients who are receiving, or have within two weeks received, monoamine oxidase inhibitors;
o Use in the presence of acute alcoholism, increased intracranial pressure or coma.
Contraindications to morphine usage which include:
o Hypersensitivity to any of the product ingredients;
o Acute respiratory depression or Chronic Pulmonary Disease;
o Excessive bronchial exudation;
o Asthma attack;
o Acute alcoholism;
o Biliary colic or following biliary tract surgery or surgical anastomosis;
o Head injuries, increased intracranial pressure or coma;
o Heart failure secondary to lung disease;
o Cyanosis;
o Convulsive disorders;
o Use in patients who are receiving, or have within two weeks received monoamine oxidase inhibitors (including moclobemide);
o Risk of paralytic ileus;
o Phaeochromocytoma;
o Blocked or traumatised nose;
o Pain not secondary to PSSC;
o Inability to secure IV access.
Kidney disease, renal dialysis;
Patient is pregnant or breastfeeding;
Patients who have any condition that would make him/her, in the opinion of the Investigator or Sponsor, unsuitable for the study; or who are, in the opinion of the Investigator, not likely to complete the study for any reason.

Exclusion Criteria - Randomisation:
All previous exclusion criteria;
Patient has received parenteral narcotic analgesic within 4 hours of ED presentation;
Saturations below 95% on initial assessment;
Altered conscious state as defined by a Glasgow Coma score less than 15;
Contraindications to fentanyl usage which include:
o Use in patients with hypersensitivity or idiosyncratic response to the active ingredient;
o Use in patients with respiratory depression, cyanosis, excessive bronchial exudation, asthma attack, or chronic pulmonary disease;
o Use in patients after operative interventions in the biliary tract;
o Use in patients who are receiving, or have within two weeks received, monoamine oxidase inhibitors;
o Use in the presence of acute alcoholism, increased intracranial pressure or coma.
Contraindications to morphine usage which include:
o Hypersensitivity to any of the product ingredients;
o Acute respiratory depression or Chronic Pulmonary Disease;
o Excessive bronchial exudation;
o Asthma attack;
o Acute alcoholism;
o Biliary colic or following biliary tract surgery or surgical anastomosis;
o Head injuries, increased intracranial pressure or coma;
o Heart failure secondary to lung disease;
o Cyanosis;
o Convulsive disorders;
o Use in patients who are receiving, or have within two weeks received monoamine oxidase inhibitors (including moclobemide);
o Risk of paralytic ileus;
o Phaeochromocytoma;
o Blocked or traumatised nose;
o Pain not secondary to PSSC;
o Inability to secure IV access.
Patient has participated in another clinical trial involving an IMP within 4 weeks of dosing, or who are currently enrolled in another clinical trial involving an IMP;
Patients who have any condition that would make him/her, in the opinion of the Investigator or Sponsor, unsuitable for the study, or who are, in the opinion of the Investigator, not likely to complete the study for any reason.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of this study is the measurement of difference in pain score reduction between study arms, on age-appropriate numeric pain rating scales, measured 10 minutes after administration of study medication.

E.5.1.1

Timepoint(s) of evaluation of this end point

10 minutes after administration of study medication.

E.5.2

Secondary end point(s)

The secondary endpoints of this study include:
Measurement of time to analgesic effect as defined by time to reduction in pain from severe (7-10) to:
o Moderate
o Mild and
o No pain
Measurement of the need for rescue analgesia, defined as exacerbation of pain requiring supplemental analgesia;
Measurement of other secondary effects, including:
o Nausea and vomiting
o Measurement of respiratory depression, as defined by an age appropriate self-ventilation rate that fails to provide full ventilation and perfusion of the lungs
o Measurement of cardiovascular depression, as defined as heart rate and/or blood pressure falling below age appropriate rates in the absence of any other aetiology
o Measurement of sedation level using the University of Michigan Sedation Score

E.5.2.1

Timepoint(s) of evaluation of this end point

The secondary endpoints will be assessed over the 120 minute study period. Pain scores will be performed at 0, 5, 10, 15, 20, 30, 60 and 120 minutes after the administration of study drug. The trial will cease at 120 minutes after the administration of study drugs.

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)

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

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

Yes

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 definition of the end of the trial is 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

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)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

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.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 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 2011-12-05.

Yes

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

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Minors cannot give legally binding consent. Where appropriate they will be asked to give assent, but consent will be given by a parent/legal guardian.

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)

Once a subject has completed their participation in the study they will be treated as per standard medical practice for this patient population.

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

2012-01-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-02-14

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-11-14

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials