A Study to Compare QUTENZA With Pregabalin for the Treatment of Peripheral Neuropathic Pain (PNP) After 8 Weeks of Treatment

Phase 4

Completed

• Conditions: Non-diabetic Painful Peripheral Polyneuropathy; Peripheral Nerve Injury (PNI); Postherpetic Neuralgia (PHN)
• Interventions: Drug: Qutenza; Drug: Pregabalin

• Registration Number: NCT01713426
• Lead Sponsor: Astellas Pharma Europe Ltd.

Brief Summary

This study is comparing the efficacy and tolerability of Qutenza with that of pregabalin in patients suffering from peripheral neuropathic pain. Treatment allocation will be to one of these treatments and the duration of the study will be about 10 weeks (assuming that from screening to treatment allocation takes 2 weeks). Participants will be asked to complete questionnaires about various aspects relating to their condition throughout the study.

This study will include subjects suffering from Postherpetic Neuralgia, Peripheral Nerve Injury or Non Diabetic peripheral polyneuropathy.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-07-11
• Study First Submitted: 2012-10-22
• Study First Submitted QC: 2012-10-22
• Study First Posted: 2012-10-24
• Primary Completion: 2013-09-26
• Study Completion: 2013-09-26
• Status Verified: 2018-04
• Last Update Submitted: 2018-04-19
• Last Update Posted: 2018-04-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 568

Inclusion Criteria

• 1. Documented diagnosis of probable or definite PNP
• 2. Localized and well-defined area of PNP, suitable for treatment with QUTENZA
• 3. Documented diagnosis at the Baseline Visit of either:
  • Postherpetic neuralgia (PHN) with pain persisting at least 6 months since shingles vesicle crusting
  • Peripheral nerve injury (PNI) including post-surgical or post-traumatic neuropathic pain, persisting for a minimum of 3 months
  • Non-diabetic painful peripheral polyneuropathy with pain which has persisted for a minimum of 3 months, including (i) small-fiber neuropathy, as confirmed by quantitative sensory testing (QST), laser evoked potentials (LEP) 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
• 4. 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" Numeric Pain Rating Scale (NPRS) score
• 5. Intact, non-irritated, dry skin over the painful area(s) to be treated
• 6. Is either:
  • Naïve to treatment with pregabalin and gabapentin, OR
  • In the opinion of the investigator, has not received an adequate trial of treatment with pregabalin or gabapentin
• 7. Subject is willing to receive pregabalin or QUTENZA as part of the trial
• 8. 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

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Qutenza	Qutenza	Cutaneous patch
Pregabalin	Pregabalin	Oral capsule

Primary Outcome Measures

Name	Time	Method
Proportion of subjects in each arm who achieve at least 30% decrease in the "average pain for the past 24 hours" Numeric Pain Rating Scale (NPRS) score from baseline to week 8	Baseline and week 8

Secondary Outcome Measures

Name	Time	Method
Proportion of subjects in each arm who achieve "optimal Therapeutic effect"	Baseline and week 8	Optimal therapeutic effect is defined as: * No change in background chronic pain medication and no discontinuation of study drug due to lack of efficacy or tolerability prior to Week 8; * At least a 30% reduction in the "average pain for the past 24 hours" NPRS score, from baseline to Week 8, and; * No moderate or severe adverse drug reactions (ADRs) during the stable Treatment Period
Proportion of subjects who achieve at least a 30% decrease in the "average pain for the past 24 hours"	Baseline to Week 8	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"	Baseline to Week 8	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"	Baseline to Week 8	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)	Up to 8 weeks	Assessed by at least a 30% reduction in "average pain for the past 24 hours" NPRS score
Overall subject status using Patient Global Impression of Change (PGIC) questionnaire	At Weeks 4 and 8
Change in the Medical Outcomes Study (MOS) 6-Item Cognitive Functioning Scale	Baseline to Week 8
MOS - Sleep Scale	Baseline to Weeks 4 and 8
Change in the EQ-5D-5L (Euroqol-5 dimensions-5 levels) total score	Baseline to Week 8
Treatment satisfaction	Baseline to Weeks 4 and 8	As assessed by: * Proportion of subjects who discontinue study drug or withdraw from the study due to either a lack of efficacy or tolerability; * Treatment Satisfaction Questionnaire for Medication (TSQM) questionnaire at Week 4 and Week 8
Treatment satisfaction - continuance of treatment	Week 8	As assessed by willingness to continue treatment at Week 8
Time to reach optimal maintenance dose for pregabalin	Baseline to Week 8
Healthcare Resource use	Baseline to Week 8	Number of contacts with health professionals
Tolerability (Assessed by the number, severity and duration of ADRs)	Baseline to Week 8	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	Baseline to Week 8
Changes in sensory symptoms	Baseline to Week 8	Assessed using Neuropathic Pain Symptom Inventory (NPSI) scores
Reduction in pain	Baseline to Week 8	By the pattern of sensory symptoms as defined using NPSI scores at baseline.

Trial Locations

Locations (98)

Site 325 Pamukkale University Medical Faculty Hospital; 🇹🇷 Denizli, Turkey

Site 163 ORTON Invalidisaatio; 🇫🇮 Helsinki, Finland

Site 203 Aretaieio/Maginio Hospital; 🇬🇷 Athens, Greece

Site 112 Wilhelminenspital; 🇦🇹 Vienna, Austria

Site 121 Vitebsk Regional Clinical Hospital # 1; 🇧🇾 Vitebsk, Belarus

Site 131 UZ Brussels; 🇧🇪 Brussels, Belgium

Site 134 Grand Hospital de Charleroi; 🇧🇪 Charleroi, Belgium

Site 136 UZ Pellenberg; 🇧🇪 Pellenberg, Belgium

Site 116 Krankenhaus der Barmherzigen B; 🇦🇹 Graz, Austria

Site 138 Cliniques Universitaires Saint; 🇧🇪 Bruxelles, Belgium

Site 137 Univ. Ziekenhuis Antwerpen; 🇧🇪 Edegem, Belgium

Site 141 Centre for Mental Health; 🇧🇬 Ruse, Bulgaria

Site 101 Medical Union 2; 🇦🇲 Yerevan, Armenia

Site 162 Vassa Central Hospital; 🇫🇮 Vaasa, Finland

Site 202 Hippokration General Hospital of Athens; 🇬🇷 Athens, Greece

Site 111 AKH Universitatsklinik; 🇦🇹 Vienna, Austria

Site 142 UMHAT - Pleven; 🇧🇬 Pleven, Bulgaria

Site 145 Military Medical Academy; 🇧🇬 Sofia, Bulgaria

Site 161 Finnmedi OY; 🇫🇮 Tampere, Finland

Site 115 Medical University Innsbruck; 🇦🇹 Innsbruck, Tyrol, Austria

Site 133 Heilig Hart Ziekenhuis; 🇧🇪 Roeselare, Belgium

Site 204 Athens Naval Hospital; 🇬🇷 Athens, Greece

Site 201 Aretaieio University Hospital; 🇬🇷 Athens, Greece

Site 278 Semashko Regional Clinical Hospital; 🇷🇺 Nizhniy Novgorod, Russian Federation

Site 144 Tokuda Hospital Sofia; 🇧🇬 Sofia, Bulgaria

Site 292 University Medical Centre Mari; 🇸🇮 Maribor, Slovenia

Site 222 A.O.U Ospedali Riuniti; 🇮🇹 Foggia, Italy

Site 225 Policlinico San Donato; 🇮🇹 Milano, Italy

Site 232 Ospedale Niguarda Ca' Granda; 🇮🇹 Milan, Italy

Site 103 Scientific research Institute of physiotherapy; 🇦🇲 Yerevan, Armenia

Site 102 Medical Center Erebuni; 🇦🇲 Yerevan, Armenia

Site 221 FONDAZIONE S.MAUGERI I.R.C.C.S; 🇮🇹 Pavia, Italy

Site 228 Azienda Ospedaliero di Perugia; 🇮🇹 Perugia, Italy

Site 146 MHAT Alexandrovska Hospital; 🇧🇬 Sofia, Bulgaria

Site 229 Azienda Ospedaliero di Perugia; 🇮🇹 Perugia, Italy

Site 223 AOU San Giovanni Battista; 🇮🇹 Torino, Italy

Site 175 CHU Caremeau; 🇫🇷 Nîmes, France

Site 104 Medical Center "Surb Nerses Mets"; 🇦🇲 Yerevan, Armenia

Site 114 Klinikum Klagenfurt Worthersee; 🇦🇹 Klagenfurt, Carynthia, Austria

Site 177 Hospital Roger Salengro CHRU; 🇫🇷 Lille, France

Site 153 Klinika anesteziologie; 🇨🇿 Praha, Czechia

Site 172 Hospital Saint Antoine; 🇫🇷 Paris, France

Site 227 Azienda Ospedaliera Universita; 🇮🇹 Firenze, Italy

Site 173 CHU Hopital Nord; 🇫🇷 Saint-Etienne, France

Site 132 Ziekenhuis Oost-Limburg; 🇧🇪 Genk, Belgium

Site 151 Fakultni nemocnice Plzen; 🇨🇿 Plzen, Czechia

Site 147 MHAT Sv. Ivan Rilski; 🇧🇬 Sofia, Bulgaria

Site 192 Universitätsklinikum Giessen; 🇩🇪 Gießen, Germany

Site 194 Schmerz Palliativznt Wiesbaden; 🇩🇪 Wiesbaden, Germany

Site 171 Hospital Ambroise Pare; 🇫🇷 Boulogne Billancourt, France

Site 174 Hopital Neurologique Pierre W; 🇫🇷 Bron, France

Site 176 CH Regional de Valence; 🇫🇷 Valence, France

Site 213 Semmelweis Egyetem Molekuláris Neurológiai Klinikai és Kutatási Központ; 🇭🇺 Budapest, Hungary

Site 231 Ospedale S. Chiara; 🇮🇹 Pisa, Italy

Site 226 Presidio Ospedale G.Mazzini; 🇮🇹 Teramo, Italy

Site 245 Poradnia Leczenia Bólu, Uniwer; 🇵🇱 Gdańsk, Poland

Site 241 Tomasz Dąbrowski Śląskie Centr; 🇵🇱 Katowice, Poland

Site 262 Spitalul Clinic Judetean de Ur; 🇷🇴 Constanta, Romania

Site 266 Spitalul Clinic de Urgenta "Pr; 🇷🇴 Iasi, Romania

Site 312 Karolinska University Hospital; 🇸🇪 Stockholm, Sweden

Site 246 NZOZ Poradnia Leczenia Bolu Pr; 🇵🇱 Tychy, Poland

Site 264 Spitalul Clinic Colentina; 🇷🇴 Bucuresti, Romania

Site 230 Azienda Ospedaliera SantaMaria; 🇮🇹 Terni, Italy

Site 323 Ege University Medical Faculty Hospital; 🇹🇷 Izmir, Turkey

Site 244 Niepubliczny Zakład Opieki Zdr; 🇵🇱 Gdańsk, Poland

Site 243 NZOZ Poradnia Leczenia Bólu; 🇵🇱 Gdynia, Poland

Site 242 NZOZ Centrum Medyczne; 🇵🇱 Warszawa, Poland

Site 254 Hospital Fernando Fonseca; 🇵🇹 Amadora, Portugal

Site 253 CHS - Hosp. S. Bernardo; 🇵🇹 Setúbal, Portugal

Site 252 Instituto Portuges de Oncologic; 🇵🇹 Lisboa, Portugal

Site 276 OOO Clinical Neurology Center; 🇷🇺 Novosibirsk, Russian Federation

Site 274 Saint-Petersburg State Medical University; 🇷🇺 Saint-Petersburg, Russian Federation

Site 271 First Moscow State Medical University named after I.M. Sechenov; 🇷🇺 Moscow, Russian Federation

Site 272 City Clinical Hospital # 12; 🇷🇺 Moscow, Russian Federation

Site 263 Spitalul Clinic Judetean de Ur; 🇷🇴 Timisoara, Romania

Site 273 Military Medical Academy; 🇷🇺 Saint-Petersburg, Russian Federation

Site 282 Neurological surgery; 🇸🇰 Bratislava, Slovakia

Site 313 SU/Östra; 🇸🇪 Göteborg, Sweden

Site 334 Seacroft Hospital; 🇬🇧 Leeds, United Kingdom

Site 311 Karolinska University Hospital; 🇸🇪 Stockholm, Sweden

Site 277 Hospital №40 of Kurortniy; 🇷🇺 Saint-Petersburg, Russian Federation

Site 283 SANERA, s.r.o.; 🇸🇰 Presov, Slovakia

Site 281 AB-BA ambulancia; 🇸🇰 Bratislava, Slovakia

Site 332 Gartnavel General Hospital; 🇬🇧 Glasgow, United Kingdom

Site 333 St Thomas' Hospital; 🇬🇧 London, United Kingdom

Site 331 The Walton Centre; 🇬🇧 Liverpool, United Kingdom

Site 303 Hospital Universitario Virgen; 🇪🇸 Granada, Spain

Site 324 Dokuz Eylul University Medical Faculty Hospital; 🇹🇷 Izmir, Turkey

Site 335 The Christies NHS Foundation; 🇬🇧 Manchester, United Kingdom

Site 301 Hospital General Universitario de Alicante; 🇪🇸 Alicante, Spain

Site 336 Leicester Royal Infirmary; 🇬🇧 Leicester, United Kingdom

Site 326 Maramara University, Pendik Training and Research Hospital; 🇹🇷 Istanbul, Turkey

Site 200 Prax S.Wolf u.B.Schütz Pal.med; 🇩🇪 Cottbus, Germany

Site 193 Universitätsklinikum Münster; 🇩🇪 Münster, Germany

Site 197 Universitätsklinikum Würzburg; 🇩🇪 Würzburg, Germany

Site 261 Quantum Medical Center SRL; 🇷🇴 Bucuresti, Romania

Site 265 Spit Clin Judetean de Urgenta; 🇷🇴 Targu Mures, Romania

Site 321 Hacettepe University Medical Faculty Hospital; 🇹🇷 Ankara, Turkey