Clinical Trials Register

Summary
EudraCT Number:	2011-005872-41
Sponsor's Protocol Code Number:	QTZ-EC-0004
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-03-13
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

Sweden - MPA

A.2

EudraCT number

2011-005872-41

A.3

Full title of the trial

QUTENZA versus pregabalin in subjects with peripheral
neuropathic pain: an open-label, randomized, multicenter, noninferiority efficacy and tolerability study

A.3.1

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

Comparison of efficacy and safety of Qutenza vs Lyrica

A.3.2

Name or abbreviated title of the trial where available

ELEVATE

A.4.1

Sponsor's protocol code number

QTZ-EC-0004

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 Europe Ltd.
B.1.3.4	Country	United Kingdom
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 Ltd.
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Astellas Pharma GmbH
B.5.2	Functional name of contact point	Clinical Research
B.5.3	Address:
B.5.3.1	Street Address	Georg-Brauchle-Ring 64-66
B.5.3.2	Town/ city	München
B.5.3.3	Post code	80992
B.5.3.4	Country	Germany
B.5.4	Telephone number	+498945441487
B.5.5	Fax number	+498945445487
B.5.6	E-mail	regine.wentz@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 179 mg cutaneous patch
D.2.1.1.2	Name of the Marketing Authorisation holder	Astellas Pharma Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Qutenza 179 mg cutaneous patch
D.3.2	Product code	N/A
D.3.4	Pharmaceutical form	Medicated plaster
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.3.9.2	Current sponsor code	NGX-4010
D.3.9.3	Other descriptive name	CAPSAICIN
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	equal
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.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	Lyrica 75 mg hard capsules
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Ltd
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Lyrica
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Pregabalin
D.3.9.1	CAS number	148553-50-8
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	PREGABALIN
D.3.9.4	EV Substance Code	SUB10023MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	75
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 who have a documented diagnosis of probable or definite Peripheral Neuropathic Pain

E.1.1.1

Medical condition in easily understood language

Patients who have neuropathic pain due to shingles, injured nerve or a disease of a specific nerve as diagnosed by a physician

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	16.0
E.1.2	Level	LLT
E.1.2	Classification code	10054095
E.1.2	Term	Neuropathic pain
E.1.2	System Organ Class	100000004852

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 compare the efficacy of QUTENZA versus pregabalin in subjects with peripheral neuropathic pain (PNP) after 8 weeks

E.2.2

Secondary objectives of the trial

• To compare the optimal therapeutic effect of QUTENZA versus pregabalin in subjects with PNP
• To compare the:
− onset of treatment effect associated with QUTENZA or pregabalin
− tolerability of treatment with QUTENZA or pregabalin
− effect of QUTENZA or pregabalin on cognition, sleep and health related quality of life
− satisfaction with treatment with QUTENZA or pregabalin
− healthcare resource utilization following treatment with QUTENZA or pregabalin
− safety of treatment with QUTENZA or pregabalin
• To identify sensory symptoms that are predictive of a reduction in pain scores for subjects receiving QUTENZA.
• To evaluate the effect of treatment with QUTENZA or pregabalin on the intensity and area of allodynia
• To examine the impact of pain relief and treatment tolerability on health-related quality of life as determined by the relationship between relevant endpoints.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female between 18 and 80 years of age, inclusive
2. In good health as determined by the investigator
3. Documented diagnosis of probable or definite PNP (Treede et al, 2008)
4. Localized and well-defined area of PNP, suitable for treatment with QUTENZA
5. Documented diagnosis at the Baseline Visit of either:
a. Postherpetic neuralgia (PHN) with pain persisting at least 6 months since shingles vesicle crusting
b. Peripheral nerve injury (PNI) including post-surgical or post-traumatic neuropathic pain, persisting for a minimum of 3 months
c. Non-diabetic painful peripheral polyneuropathy with pain which has persisted for a minimum of 3 months, including i. small-fiber neuropathy, as confirmed by QST, laser-evoked potential or skin biopsy, ii. chemotherapy induced neuropathy in subjects with stable neoplastic disease, iii. other, adequately characterized painful peripheral polyneuropathy, based on clinical history and examination
6. Average pain score >=4 during screening period, over a minimum of at least 4 consecutive days (using the “average pain for the past 24 hours” NPRS score)
7. Intact, non-irritated, dry skin over the painful area(s) to be treated
8. Is either:
a. Naïve to treatment with pregabalin and gabapentin, OR
b. In the opinion of the investigator, has not received an adequate trial of treatment with pregabalin or gabapentin
9. Subject is willing to receive pregabalin or QUTENZA as part of the trial.
10. Females of child bearing potential must be willing to use highly effective methods of birth control during the study and for 30 days following study termination (a highly effective method of birth control is defined as those which result in a low failure rate (CHMP/ICH/286/95 modified) of less that 1% per year when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomized partner).
11. Willing and able to comply with protocol requirements for the duration of study participation
12. Given written informed consent

E.4

Principal exclusion criteria

1. Significant ongoing or recurrent pain of etiology other than PHN, PNI or non-diabetic painful peripheral polyneuropathy, for example: compression-related neuropathies (e.g. spinal stenosis), radiculopathy, tumor-related pain, fibromyalgia or arthritis
2. Complex Regional Pain Syndrome (CRPS, Type I or II)
3. Neuropathic pain related to previously administered radiotherapy, diabetes mellitus or HIV-AN
4. Neuropathic pain areas located only on the face, above the hairline of the scalp, and/or in proximity to mucous membranes
5. Severe loss of heat sensation in the painful area, indicative of C-fiber denervation
6. Reported daily pain score of 10 on the NPRS for at least 4 days during the screening period
7. Past or current history of diabetes mellitus.
8. Unstable or poorly controlled hypertension or a recent history of a cardiovascular event which, in the opinion of the investigator, would put the subject at risk of adverse cardiovascular reactions related to the patch application procedure
9. Creatinine clearance (CLcr ) < 60mL/min according to the Cockcroft-Gault formula
10. Untreated ongoing generalized anxiety disorder according to DSM-IV or ICD-10 criteria
11. Severe ongoing depression according to DSM-IV or ICD-10 criteria
12. Evidence of cognitive impairment including dementia that may interfere with subject’s ability to complete study evaluations and recall pain levels in the past 24 hours
13. Planned elective surgery during the trial
14. Changes to stable neuropathic pain background medication in the 4 weeks prior to the Baseline Visit
15. Any prior receipt of QUTENZA patches, including blinded patches administered as part of a clinical trial
16. Hypersensitivity to capsaicin (i.e., chilli peppers or Over-the-counter [OTC] capsaicin products), any QUTENZA excipients, local anesthetics, or adhesives
17. Treatment with pregabalin or gabapentin within 2 months prior to the Baseline Visit.
18. Hypersensitivity to pregabalin or any of the excipients
19. Use of opioids exceeding a total daily dose of morphine of 200 mg/day, or equivalent; or any intravenous opioids or tapentadol, regardless of dose, within 7 days preceding the Baseline Visit.
20. Use of any topical pain medication, such as non-steroidal anti-inflammatory drugs, menthol, methyl salicylate, local anesthetics (including patch containing lidocaine), steroids or capsaicin products on the painful areas to be treated within 7 days preceding the Baseline Visit
21. Chemotherapy within 3 months of the Baseline Visit, except maintenance hormone treatment
22. Use of any investigational agent within 30 days prior to Baseline Visit
23. Active substance abuse or history of chronic substance abuse within 1 year prior to screening; or any prior chronic substance abuse (including alcoholism) likely to re-occur during the study period as judged by the investigator
24. Female subjects of child-bearing potential with a positive serum or urine pregnancy test prior to treatment
25. Subject, who in the opinion of the investigator, is not suitable for the study for any reason

E.5 End points

E.5.1

Primary end point(s)

The proportion of subjects in each arm who achieve at least a 30% decrease in the “average pain for the past 24 hours” NPRS score from baseline to Week 8, without a change in background chronic pain medication.

E.5.1.1

Timepoint(s) of evaluation of this end point

wk 1-8

E.5.2

Secondary end point(s)

● Proportion of subjects in each arm who achieve “optimal therapeutic effect”.
Optimal therapeutic effect is defined as:
o No change in background chronic pain medication or discontinuation of study drug due to lack of efficacy or tolerability prior to Week 8
o At least a 30% reduction in the “average pain for the past 24 hours” NPRS score, from baseline to Week 8, and
o No moderate or severe adverse drug reactions (ADRs) during the stable treatment period (see section 5.5.4),

● Proportion of subjects who achieve at least a 30% decrease in the “average pain for the past 24 hours” NPRS score from baseline to the mean of all scores recorded between Week 1 (Day 8) and Week 8 (Day 57)
● Proportion of subjects who achieve at least a 50% decrease in the “average pain for the past 24 hours” NPRS score from baseline to week 8, and from baseline to the mean of all scores recorded between Week 1 (Day 8) and Week 8 (Day 57)
● Absolute and percent change in “average pain for the past 24 hours” NPRS score from baseline to Week 8, and from baseline to the mean of all scores recorded between Weeks 1 to 8
● Time to onset of pain relief (in days) as assessed by at least a 30% reduction in “average pain for the past 24 hours” NPRS
● Overall subject status using Patient Global Impression of Change (PGIC) questionnaire at Weeks 4 and 8
● Change in the Medical Outcomes Study (MOS) – Cognitive Functioning Scale from baseline to Week 8
● MOS Sleep Scale from baseline to Weeks 4 and 8
● Change in the EQ-5D-5L total score from baseline to Week 8
● Treatment satisfaction as assessed by:
o Proportion of subjects who discontinue study drug or withdraw from the study due to either a lack of efficacy or tolerability
o Willingness to continue treatment at Week 8
o Treatment Satisfaction Questionnaire for Medication (TSQM) questionnaire at Week 4 and Week 8
● Time to reach optimal maintenance dose for pregabalin
● Resource use (number of contacts with health professionals)
● Tolerability (assessed by the number, severity and duration of ADRs), collected as self-rated health-related complaints by the subject and then medically confirmed and causality assigned by the investigator
● Change in intensity and area of allodynia from baseline to Week 8
● Changes in sensory symptoms between baseline and Week 8 assessed using neuropathic pain symptom inventory (NPSI) scores
● Reduction in pain by the pattern of sensory symptoms as defined using NPSI scores at baseline

E.5.2.1

Timepoint(s) of evaluation of this end point

wk 1-8

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

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

Armenia

Austria

Belarus

Belgium

Bulgaria

Czech Republic

Finland

France

Georgia

Germany

Greece

Hungary

Italy

Netherlands

Poland

Portugal

Romania

Russian Federation

Slovakia

Slovenia

Spain

Sweden

Turkey

United Kingdom

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

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.1.1.1

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:

263

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

263

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

300

F.4.2.2

In the whole clinical trial

526

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)

Qutenza and pregabalin are authorized products in the Community, subjects may be prescribed the products by their physician if it is considered to be of benefit.

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

2012-04-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-04-04

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-09-26

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