Clinical Trials Register

Summary
EudraCT Number:	2011-001140-30
Sponsor's Protocol Code Number:	FYL/24019/008
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-05-25
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

Czechia - SUKL

A.2

EudraCT number

2011-001140-30

A.3

Full title of the trial

Randomized, placebo-controlled study of Fentanyl Ethypharm for breakthrough pain in opioid-treated patients with cancer.

A.3.1

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

Study placebo controlled to test the efficacy of Fentanyl Ethypharm for the treatment of exacerbated pains.

A.3.2

Name or abbreviated title of the trial where available

ETHYFYL

A.4.1

Sponsor's protocol code number

FYL/24019/008

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	Laboratoires Ethypharm
B.1.3.4	Country	France
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	Laboratoires Ethypharm
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ICTA PM
B.5.2	Functional name of contact point	Project management
B.5.3	Address:
B.5.3.1	Street Address	11 rue du Bocage
B.5.3.2	Town/ city	FONTAINE LES DIJON
B.5.3.3	Post code	21121
B.5.3.4	Country	France
B.5.4	Telephone number	33380534000
B.5.5	Fax number	33380571022
B.5.6	E-mail	contact@icta.fr

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	Fentanyl Ethypharm
D.3.2	Product code	FYL/24019
D.3.4	Pharmaceutical form	Sublingual tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Sublingual use
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.3.9.3	Other descriptive name	Fentanyl Ethypharm
D.3.9.4	EV Substance Code	SUB02129MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	133 to 800
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Sublingual tablet
D.8.4	Route of administration of the placebo	Sublingual use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Breakthrough pain related to cancer.

E.1.1.1

Medical condition in easily understood language

Exacerbated pains related to cancer

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

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	10069398
E.1.2	Term	Breakthrough cancer pain
E.1.2	System Organ Class	10018065 - General disorders and administration site conditions

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

is to assess the clinical effectiveness of Fentanyl Ethypharm when used to relieve breakthrough pain (BTP) in opioid-treated cancer patients.

E.2.2

Secondary objectives of the trial

are:
• To assess the safety and tolerability of Fentanyl Ethypharm when used to relieve BTP in opioid-treated cancer patients.
• To assess the efficacy of Fentanyl Ethypharm on the neuropathic component of BTP.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Written informed consent form obtained;
2.Is at least 18 years of age;
3.Has a documented diagnosis of a malignant solid tumor or a hematological malignancy causing cancer-related pain;
4.Has an Eastern Cooperative Oncology Group (ECOG) performance status rating 3;
5.Has a life-expectancy of at least 2 months;
6.Has been receiving between 60 mg and 1000 mg of oral morphine daily, or at least 25 μg/hour of transdermal fentanyl or at least 30 mg of oxycodone daily, or 8 mg of oral hydromorphone daily, or an equianalgesic dose of another opioid for cancer-related pain at a stable dose for at least a week;
7.Has a stable background pain intensity ≤4/10 in the pain scale for at least a week;
8.Experiencing on average, 1 to 4 episodes of breakthrough pain per day that are adequately controlled with a stable dose of standard rescue medication, of which the patient will have an adequate supply throughout the study;
9.Is willing and able (personally or with the help of a caregiver) to:
a.Evaluate and record pain intensity and pain relief and,
b.Record adverse events and,
c.Record each intake of study drug and rescue medication in a patient’s diary and,
d.Return diaries and study drugs at each visit
10.If female of childbearing potential (i.e. not surgically sterile or 1 year after the onset of amenorrhea due to menopause):
a.Has a negative urinary pregnancy test and,
b.Is not breastfeeding and,
c.Agrees to practice a reliable form of contraception or abstinence during the study.

E.4

Principal exclusion criteria

1.Hypersensitivity to fentanyl or to any of the excipients;
2.Is using intrathecal opioids;
3.Has recent history of substance abuse or neurologic or psychiatric impairment that would compromised data collection;
4.Has had recent therapy (within 30 days) or will receive a planned therapy during the study that would alter pain or response to analgesics during the study such as palliative radiation therapy or a nerve block;
5.Has a known moderate or severe hepatic or renal disease*;
6.Has received any other investigational new drug within 30 days before the first study drug administration;
7.Has sleep apnea or active brain metastases with increase intracranial pressure;
8.Is at risk of increased opioid side effects because of prior or concomitant medications (such as CYP3A4 inhibitors, partial opioid agonists/antagonists);
9.Is at risk of significant bradyarrythmia because of underlying heart disease;
10.Has primary source breakthrough pain that is not cancer related;
11.Treated by Mono Amine Oxydase Inhibitor (MAOI), or last MAOI intake within last 2 weeks;
12.Has a severe chronic obstructive pulmonary disease or severe respiratory depression.

E.5 End points

E.5.1

Primary end point(s)

The Pain Intensity (PI) will be measured with an eleven-point numerical pain rating scale (0=no pain and 10=worst pain).

E.5.1.1

Timepoint(s) of evaluation of this end point

Patients will be rated their PI immediately prior to the administration of IMP and at 3, 6, 10, 15, 30 and 60 minutes post-dose.

E.5.2

Secondary end point(s)

Pain Relief (PR) will be measured with a five-point numerical rating scale (0=none; 1=slight; 2=moderate; 3=a lot; 4=complete).

E.5.2.1

Timepoint(s) of evaluation of this end point

This outcome will be assessed at 3, 6, 10, 15, 30 and 60 minutes after administration of each intake of IMP

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

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

E.8.1.5

Parallel group

E.8.1.6

Cross over

Yes

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Open label then double-blind

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

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

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

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

F.1.1