Clinical Trials Register

Summary
EudraCT Number:	2009-016458-42
Sponsor's Protocol Code Number:	E05-CL-3002
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-01-13
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

2009-016458-42

A.3

Full title of the trial

A Randomized, Controlled, Long-term Safety Study Evaluating the Effect of Repeated Applications of QUTENZA plus Standard of Care versus Standard of Care alone in Subjects with Painful Diabetic Peripheral Neuropathy

Studio randomizzato controllato per la valutazione della sicurezza a lungo termine di applicazioni ripetute di QUTENZATM piu' terapia standard (TS) versus sola terapia standard nei pazienti affetti da neuropatia diabetica periferica dolorosa (NDP dolorosa)

A.3.1

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

A safety study in which multiple applications of Qutenza combined with standard treatment is compared to standard treatment alone in patient with diabetic nerve pain at the feet.

Studio di sicurezza in cui si confronta ripetute applicazioni di Qutenzam piu' terapia standard con la sola terapia standard in pazienti diabetici con dolore localizzato ai nervi del piede

A.3.2

Name or abbreviated title of the trial where available

PACE

A.4.1

Sponsor's protocol code number

E05-CL-3002

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	ASTELLAS PHARMA
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	Astellas Pharma Europe B.V
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Astellas Pharma Europe B.V
B.5.2	Functional name of contact point	Service Desk
B.5.3	Address:
B.5.3.1	Street Address	Global Development Operations, Elisabethhof 19
B.5.3.2	Town/ city	Leiderdorp
B.5.3.3	Post code	2353 EW
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31 (0)71 54 55 878
B.5.5	Fax number	+31 (0)71 54 55 224
B.5.6	E-mail	contact@nl.astellas.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	Yes
D.2.1.1.1	Trade name	Qutenza
D.2.1.1.2	Name of the Marketing Authorisation holder	Astella Pharma Europa B.V
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	Cutaneous patch
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Cutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CAPSAICIN
D.3.9.1	CAS number	404-86-4
D.3.9.4	EV Substance Code	SUB13229MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	179
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

Painful Diabetic Peripheral Neuropathy

neuropatia diabetica periferica dolorosa

E.1.1.1

Medical condition in easily understood language

Diabetic nerve pain

Nevralgia diabetica

E.1.1.2

Therapeutic area

Health Care [N] - Population Characteristics [N01]

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	10012683
E.1.2	Term	Diabetic peripheral neuropathy
E.1.2	System Organ Class	10029205 - Nervous system disorders

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 assess the safety of repeat applications of QUTENZA administered over a period of 12 months in subjects with PDPN

• Valutare la sicurezza di QUTENZA somministrato mediante applicazioni ripetute per un periodo di 12 mesi in pazienti affetti da NDP dolorosa

E.2.2

Secondary objectives of the trial

To assess the efficacy of repeat applications of QUTENZA administered over a period of 12 months in subjects with PDPN

• Valutare l’efficacia di QUTENZA somministrato mediante applicazioni ripetute per un periodo di 12 mesi in pazienti affetti da NDP dolorosa

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Independent Ethics Committee (IEC)-approved written Informed Consent and privacy language as per national regulations must be obtained from the subject or legally authorized representative prior to any study-related procedures 2. Male or female >18 years of age 3. Diagnosis of painful, distal, symmetrical, sensorimotor polyneuropathy which is due to diabetes 4. Stable glycemic control for at least 6 months prior to screening visit 5. Average Numeric Pain Rating Scale (NPRS) score over the last 24 hours of >4 at the screening and the baseline visit

1. Prima di essere sottoposto a qualsiasi procedura di studio (compresa la sospensione, ove applicabile, dei farmaci non consentiti) il paziente o un suo rappresentante legale dovranno firmare il Consenso informato scritto approvato dal Comitato Etico indipendente (IEC) e le dichiarazioni sulla privacy richieste dalle normative nazionali 2. Paziente di sesso maschile o femminile di età >18 anni 3. Diagnosi di polineuropatia sensomotoria distale simmetrica dolorosa di origine diabetica, 4. Controllo glicemico stabile per un periodo minimo di 6 mesi prima della Visita di Screening 5. Punteggio medio di >4 alla NPRS (Scala numerica per la valutazione del dolore) applicata alle ultime 24 ore prima della Visita di Screening e della Visita Basale

E.4

Principal exclusion criteria

1. Primary pain associated with PDPN in the ankles or above 2. Pain that could not be clearly differentiated from, or conditions that might interfere with, the assessment of PDPN 3. Significant pain (moderate or above) of an etiology other than PDPN, that may interfere with judging PDPN-related pain 4. Female subjects of childbearing potential must have a negative serum or urine pregnancy test at enrollment and must agree to maintain highly effective birth control during the study. 5. Hypersensitivity to capsaicin (i.e., chili peppers or over-the-counter [OTC] capsaicin products), any QUTENZA excipients, EMLA ingredients or adhesives

1. Il dolore principale associato alla NDP dolorosa è a carico delle caviglie o della zona superiore 2. Presenza di uno disturbo, in grado di interferire con la valutazione della NDP dolorosa o di impedire un’identificazione univoca della causa del dolore: 3. Dolore significativo (di intensità moderata o superiore) di eziologia diversa dalla NDP in grado di interferire con la valutazione del dolore provocato dalla NDP dolorosa 4. Al momento dell’arruolamento le pazienti di sesso femminile in età fertile dovranno risultare negative al test di gravidanza su siero o su urine e dovranno accettare di adottare un metodo anticoncezionale ad efficacia elevata durante il corso dello studio. 5. Ipersensibilità alla capsaicina (cioè al peperoncino o ai prodotti da banco [OTC] a base di capsaicina), a uno qualsiasi degli eccipienti di QUTENZA, agli ingredienti della crema EMLA o agli adesivi

E.5 End points

E.5.1

Primary end point(s)

Percentage change in health related quality of life (HRQOL) total score as assessed by the disease specific Norfolk scale from baseline to endpoint (discontinuation or End of Study [EoS] visit).

• Variazione percentuale del punteggio complessivo relativo alla qualità della vita connessa alla salute (HRQOL), valutata mediante la specifica scala Norfolk, dal basale all’endpoint (Visita di Interruzione [ET] o di Fine Studio [EoS]).

E.5.1.1

Timepoint(s) of evaluation of this end point

baseline to endpoint (discontinuation or end of study visit)

Baseline all'endpoint (interruzione o fine dello studio)

E.5.2

Secondary end point(s)

• Neurological function as assessed by the UENS and sensory testing • Tolerability of patch application by: - dermal assessment (0–7 point severity score on dermal assessment scale); and - ''pain now'' NPRS scores after patch application - rescue medication use on days 1 through 5 • Adverse events and serious adverse events (SAEs) • Vital signs (heart rate and blood pressure) associated with patch application • Laboratory analyses • Intensity of neuropathic pain using ''average pain'' NPRS scores (Question 5 of BPI-DN form) • BPI pain severity index and pain interference index • Patient Global Impression of Change (PGIC) • Generic HRQOL measured by European Quality of Life – 5 Dimensions (EQ- 5D) questionnaire. • Treatment satisfaction using the Self-Assessment of Treatment (SAT) questionnaire

● Funzione neurologica valutata mediante scala UENS e test sensoriali ● Tollerabilità dell’applicazione del cerotto mediante: o valutazione dermatologica (scala con indice di gravità da 0 a 7); e o “dolore attuale” mediante scala NPRS dopo l’applicazione del cerotto o uso di farmaci di salvataggio dal giorno 1 al giorno 5 ● Eventi avversi (AE) ed eventi avversi gravi (SAE) ● Segni vitali (frequenza cardiaca e pressione ematica) associati all’applicazione del cerotto ● Analisi di laboratorio ● Intensità del dolore neuropatico valutato mediante punteggi della scala NPRS relativi al “dolore medio” (domanda 5 del BPI-DN) ● Indice di intensità e di interferenza del dolore al BPI ● Percezione complessiva della variazione del dolore (Patient Global Impression of Change - PGIC) ● HRQOL generica, misurata mediante Questionario europeo sulla qualità della vita a 5 dimensioni (EQ-5D). ● Soddisfazione per il trattamento valutata mediante questionario SAT (Autovalutazione del trattamento)

E.5.2.1

Timepoint(s) of evaluation of this end point

baseline to endpoint (discontinuation or end of study visit)

Baseline all'endpoint (interruzione o fine dello 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

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Russian Federation

Ukraine

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 patient last visit

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

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)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

180

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

270

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

312

F.4.2.2

In the whole clinical trial

450

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)

Patients will revert to normal standard of care treatment at end of trial.

Alla fine dello studio i pazienti torneranno al loro trattamento standard normale

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

2012-04-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-12-15

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-02-27

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