Clinical Trials Register

Summary
EudraCT Number:	2013-001271-20
Sponsor's Protocol Code Number:	MOLT-2013-02
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2013-06-14
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2013-001271-20

A.3

Full title of the trial

A multicenter randomized open trial to evaluate the efficacy of fentanyl pectin nasal spray (FPNS) versus Physician Choice (PC) - Usual Care (UC), in reducing incidental predictable breakthrough pain (IP-BTP) at swallowing in patients with head and neck cancer undergoing radiotherapy

Studio multicentrico, randomizzato in aperto che ha l’obiettivo di valutare l’efficacia del Fentanyl Pectin Spray Nasale (FPNS) rispetto ai trattamenti utilizzati nella normale pratica clinica, nel ridurre il dolore episodico intenso prevedibile associato alla deglutizione nei pazienti con tumore testa e collo in trattamento con radioterapia

A.3.1

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

A multicenter randomized open trial to evaluate the efficacy of fentanyl pectin nasal spray (FPNS) versus Physician Choice (PC) - Usual Care (UC), in reducing uncontrolled pain at swallowing (moderate/severe intensity) in patients with head and neck cancer undergoing radiotherapy.

A.3.2

Name or abbreviated title of the trial where available

PE.R.F.E.C.T. F.A.S.T STUDY PEctin Rapid Fentanil Efficacy Clinical Trial For pAin at Swallowing und

A.4.1

Sponsor's protocol code number

MOLT-2013-02

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	L. Molteni & C dei F.lli Alitti Società di Esercizio S.p.A.
B.1.3.4	Country	Italy
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	L. Molteni & C. dei F.lli Alitti Società di Esercizio S.p.A.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	L. Molteni & C. dei F.lli Alitti Società di Esercizio S.p.A.
B.5.2	Functional name of contact point	Clinical Trial Manager
B.5.3	Address:
B.5.3.1	Street Address	Strada Statale 67 – Loc. Granatieri
B.5.3.2	Town/ city	Scandicci
B.5.3.3	Post code	50018
B.5.3.4	Country	Italy
B.5.6	E-mail	i.corti@moltenifarma.it

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	Pecfent nasal spray
D.2.1.1.2	Name of the Marketing Authorisation holder	Archimeds Development Ltd
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	PecFent 100mcg
D.3.2	Product code	not applicable
D.3.4	Pharmaceutical form	Nasal spray, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Nasal use
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	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	Pecfent nasal spray
D.2.1.1.2	Name of the Marketing Authorisation holder	Archimeds Development Ltd
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	PecFent 400mcg
D.3.2	Product code	not applicable
D.3.4	Pharmaceutical form	Nasal spray, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Nasal use
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with head and neck cancer undergoing radiotherapy with uncontrolled pain at swallowing (moderate/severe intensity).

Dolore alla deglutizione nei pazienti con tumore testa-collo in trattamento con radioterapia e/o chemioterapia.

E.1.1.1

Medical condition in easily understood language

Patients with head and neck cancer undergoing radiotherapy with uncontrolled pain at swallowing

i pazienti in studio, sono sottoposti a radioterapia e/o chemioterapia e hanno sviluppato dolore alla deglutizione

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.0
E.1.2	Level	LLT
E.1.2	Classification code	10042648
E.1.2	Term	Swallowing painful
E.1.2	System Organ Class	100000004856

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to assess the efficacy of Fentanyl pectin nasal spray (FPNS) compared with Physician Choice-Usual Care (PC-UC) in the management of swallowing IP-BTP in head and neck cancer patients undergoing radiotherapy with or without chemotherapy.

Valutare l’efficacia del Fentanyl spray nasale (FPNS), rispetto al trattamento utilizzato dal medico nella normale pratica clinica (PC-UC), nella gestione del dolore alla deglutizione (IP-BTP) nei pazienti con tumore testa-collo sottoposti a radioterapia con o senza chemioterapia.

E.2.2

Secondary objectives of the trial

The secondary objectives are the evaluation of the effect of FPNS versus PC-UC in respect to:
• time to reach the maximal pain reduction after administration of FPNS/PC-UC (evaluation of reduction in pain intensity score at each time point: 10,20,30 min after assuming FPNS or PC-UC )
• clinically meaningful pain reduction
• patient’s pain relief
• administration of rescue medication
• patient’s dysphagia
• safety and tolerability

Confrontare le due strategie di trattamento (FPNS vs PC-UC) rispetto a:
• tempo dalla somministrazione del farmaco necessario per avere la massima riduzione dell’intensità del dolore
• sollievo, clinicamente rilevante, dal dolore
• sollievo dal dolore riferito dal paziente
• utilizzo di una “terapia di salvataggio” (rescue medication)
• disfagia
• profilo di sicurezza e tollerabilità

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male and female aged 18 years or over
2. Diagnosis of stage III-IV cancer of oral cavity, oropharynx, hypopharynx, larynx, salivary gland cancer
3. Receiving radiation therapy (RT) with or without concurrent platinum based chemotherapy or cetuximab as first line treatment or as postoperative adjuvant treatment
4. Background pain managed with a stable fixed dose of opioid equivalent to 60mg oral morphine daily
5. Uncontrolled pain (IP-BTP) during swallowing with an intensity ≥4 on an 11-point numeric scale (0=no pain; 10=worst possible pain). This pain will have to be measured with the ingestion of a solid/liquid food (depending on the ability to swallow or less solid foods of the patient at moment)
6. Patients able to receive a nasal spray therapy
7. Willing and able to sign an informed consent form
8. Females with childbearing potential must provide a negative pregnancy test and both males and females must be using adequate contraception during the study

• Maschi e femmine con più di 18 anni
• Diagnosi di cancro (stadio III-IV) del cavo orale, orofaringe, ipofaringe, laringe, cancro alle ghiandole salivari.
• Trattamento con radioterapia con o senza concomitante chemioterapia con platino o cetuximab come prima linea di trattamento o come trattamento adiuvante post-operatorio.
• Pazienti in grado di ricevere una terapia con spray nasale
• Pazienti in grado di comprendere e firmare il consenso informato alla partecipazione allo studio.
• Donne in età fertile con test di gravidanza negativo; i pazienti (uomini e donne) inclusi nello studio devono usare un adeguato metodo contraccettivo durante lo studio
• Pazienti con dolore di base controllato con una dose di oppiodi equivalente a 60 mg di morfina orale al giorno
• Pazienti con dolore non controllato alla deglutizione di intesità ≥4 punti misurato con una scala NRS 0-10 (0= nessun dolore alla deglutizione; 10 = il peggior dolore alla deglutizione).

E.4

Principal exclusion criteria

1. Patients with known metastatic disease.
2. Known hypersensitivity to opioids, to Fentanyl or to drugs used in the PC-UC, and/or to study medications’ formulation ingredients.
3. Patients with impaired chemistry laboratory exams, assessed as routine clinical practice before radiotherapy start:
a. Hepatic function:
i. Total bilirubin > 2 times the upper-normal limit (ULN)
ii. Serum transaminase > 5 times ULN
b. Renal function:
i. Serum creatinine concentration > 2 times ULN
4. Pregnant or breastfeeding women.
5. Patients unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study.
6. Patients planned to receive other investigational treatments during study period
7. Patients with moderate to severe respiratory impairment

• Pazienti con cancro metastatico
• Ipersensibilità nota agli oppioidi , al Fentanil , e ai farmaci usato nella PC-UC (principi attivi ed eccipienti)
• Pazienti con esami clinici, eseguiti nella normale pratica clinica prima dell’inizio della radioterapia, che hanno evidenziato le seguenti disfunzioni:
a) Insufficienza epatica:
- Biliribuna totale > 2 volte il valore soglia massimo
- Transaminasi sieriche > 5 volte il valore soglia massimo
b) Insufficienza renale:
- Creatinina sierica > 2 il valore soglia massimo
• Donne in gravidanza o allattamento
• Pazienti che non sono in grado di comprendere lo studio o la natura,
lo scopo e le possibili conseguenze dei trattamenti in studio.
• Pazienti che ricevono durante il periodo di studio (o per i quali è stato pianificato ricevere) un altro trattamento sperimentale nell’ambito di un altro studio clinico.
• Pazienti con moderato o grave danno respiratorio.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the difference in the mean intensity of IP-BTP related to swallowing from the baseline to 20 minutes after taking FPNS/PC-UC (PID20).

Differenza nell’intensità media del dolore alla deglutizione (IP-BTP) tra il baseline e 20 minuti dopo l’assunzione del farmaco (PID20) tra il gruppo trattato con FPNS e quello con PC-UC

E.5.1.1

Timepoint(s) of evaluation of this end point

At the first bite/sip of the meal, patients will record the pain intensity (baseline pain) according to an 11-NRS; after this, the patient will take the FPNS/PC-UC and wait 10 minutes before start the meal. Pain intensity related to primary efficacy endpoint will be measured at 20 after drug administration.
The intensity of IP-BTP related to swallowing will be measured 3 times a day (at breakfast, lunch and dinner) by NRS for 15 episodes (no more than 3 episodes / day) in 5/6 consecutive days. The mean PID20 across treatment episodes will be used for the analyses.

L’intensità del dolore alla deglutizione viene misurata ai 3 pasti principali (colazione, pranzo, cena) per 5/6 giorni consecutivi.
Ogni paziente raccoglie i dati relativi a 15 episodi di IP-BTP (ogni episodio corrisponde ad un pasto).
Per ogni pasto il paziente dovrà registrare:
- il dolore al baseline, ossia al primo boccone o sorso (prima dell’assunzione del trattamento)
- il dolore durante il pasto registrato a 20 minuti dopo l’assunzione del trattamento.

E.5.2

Secondary end point(s)

The secondary end points are the evaluation of the effect of FPNS versus PC-UC in respect to:
• time to reach the maximal pain reduction after administration of FPNS/PC-UC (evaluation of reduction in pain intensity score at each time point: 10,20,30 min after assuming FPNS or PC-UC )
• clinically meaningful pain reduction
• patient’s pain relief
• administration of rescue medication
• patient’s dysphagia
• safety and tolerability

Confrontare le due strategie di trattamento (FPNS vs PC-UC) rispetto a:
1. Differenza nell’intensità media del dolore alla deglutizione (IP-BTP) tra il baseline e 10, 30 minuti dopo l’assunzione del farmaco
2. Tempo dopo la somministrazione del farmaco in cui si raggiunge la riduzione massima dell’intensità del dolore rispetto al baseline
3. Sollievo clinicamente rilevante dal dolore
4. Sollievo dal dolore riferito dal paziente
5. Uso di una “terapia di salvataggio” ( dose e frequenza)
6. Disfagia
7. Sicurezza e tollerabilità

E.5.2.1

Timepoint(s) of evaluation of this end point

The secondary efficacy endpoints are:
• The difference in the mean intensity of IP-BTP related to swallowing from the baseline to 10 and 30 minutes after taking FPNS/PC-UC.
• Time to reach the maximal pain reduction after administration of FPNS/PC-UC (at each time point: 10,20,30 min)
• Patient’s pain relief will be measured at the end of the study period through the 5-points numeric scale.
• Clinically meaningful pain reduction will be analyzed by assessing percentages of episodes with ≥ 2 point reductions after drug treatment versus baseline
• Administration of rescue medication (dose and frequency).
• Patient’s dysphagia assessment. An evaluation of disphagia by MDADI questionnaire will be performed at baseline and at the end of the study period.

1. Per ogni pasto il paziente dovrà registrare il dolore al baseline e a 10 e 30 min dopo l’assunzione del FPNS/PC-UC.
2. Il tempo in cui si raggiunge la riduzione massima dell’intensità del dolore: a 10, 20, 30 minuti dopo dopo l’assunzione del FPNS/PC-UC.
3. Il sollievo dal dolore clinicamente rilevante: la percentuale di episodi in cui si registra una riduzione ≥ 2punti dell’intensità del dolore
4. Il sollievo dal dolore riferito dal paziente: somministrazione a fine studio di una scala a 5 punti.
5. La frequenza e la dose della terapia di salvataggio verrà registrata nel periodo di studio
6. La disfagia: somministrazione al paziente del questionario MDADI al baseline e a fine studio
7. La sicurezza e tollerabilità dei trattamenti saranno monitorati nei 5/6 giorni di studio.

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Trattamento farmacologico utilizzato per il controllo del dolore alla deglutizione nei pazienti con

Physician choice-Usual care (PC-UC) will be any drug used in the current clinical practice for treat

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

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

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)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

100

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

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

158

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)

After the end of the study, each patient will be treated according to clinical practice for each center

Dopo la conclusione dello studio, ogni paziente sarà trattato in accordo alla normale pratica clinica.

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

2013-08-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-06-25

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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IMP with orphan designation in the indication
Orphan Designation Number:
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