Comparison of Qutenza (8% Capsaicin) With a Low-dose Capsaicin for Treatment of Nerve Pain After Surgery

Inclusion Criteria:

General

1. The subject has given written informed consent to participate.

2. Female or male subjects aged 18 years or older.

3. For women of childbearing potential: negative pregnancy tests at Screening Visit (Visit 1), the Randomization Visit (Visit 2), and prior to each reapplication of theinvestigational medicinal product (IMP), and must have agreed to practice medicallyacceptable methods of birth control. Confirmation of diagnosis of chronic moderate to severe PSNP

4. Documented diagnosis of PSNP by the following criteria:

5. A history of post-surgical pain with a duration of at least 6 months tomaximally 60 months that is plausibly related to the surgical intervention asdocumented on a body map.

6. Douleur Neuropathique 4 interview (DN4i) of at least 3 out of 7 points at Visit

8. The pain must extend beyond the scar area to neuroanatomically adjacent skinareas and be related to the site of the surgery.

9. Documented diagnosis of probable or definite PSNP according to the followingcriteria (Finnerup et al. 2016):

10. The pain must be associated with sensory signs in the same neuroanatomicallyplausible distribution. The area of sensory changes may extend beyond, bewithin, or overlap with the area of pain (criterion for probable neuropathicpain), or

11. In addition to 5a : Direct surgical evidence (e.g., surgeon´s clearverification of an intraoperative nerve lesion) (criterion for definiteneuropathic pain).

12. The subject has moderate to severe pain with a baseline value for 24-hr average painintensity of at least 4 points on the NPRS. The baseline value is calculated as theaverage of the 24-hr average pain intensity ratings of the Baseline Phase (Day -7 toDay -1). At least 5 (out of the last 7 days) pain ratings should be available duringthe Baseline Phase. If less than 5 pain ratings are available in the last 7 days,the subject may be rescheduled for Visit 2 (1 time only) after having receivedappropriate re-training in the use of the e-diary to ensure compliance. Suitability for treatment with IMP

13. The size of the affected painful intact skin area is not larger than the size of 4standard Qutenza topical systems (1120 cm2).

14. The skin in the area where the IMP will be applied, and that may also contain thescar tissue, is intact, dry, and non-irritated (i.e., there are no signs andsymptoms of skin disease, skin irritation, inflammation or injury, such as activeherpes zoster lesions, atopic dermatitis, ulceration, wounds). This is reflected bya dermal assessment score of 0 = "no evidence of irritation" or 1 = "minimalerythema, barely perceptible". Eligibility with regard to protocol adherence, to allowed pre-treatments andconcomitant treatments

15. The subject is willing to adhere to the restricted use of concomitant treatments .

16. The subject experiencing pain is:

17. currently not receiving treatment for PSNP or

18. receives a stable systemic treatment for PSNP that started more than 30 daysprior to the Randomization Visit (Visit 2).

Non-exhaustive list of examples of types of surgeries with resulting PSNP:

Thoracic surgery Breast surgery Abdominal surgery (cholecystectomy, appendectomy) Donor nephrectomy Gynecologic surgery (hysterectomy, C-section) Varicose vein surgery Inguinal herniotomy Lipoma removal Knee surgery Knee arthroplasty Ankle surgery

Exclusion Criteria:

General or previous treatments

1. The subject received Qutenza before the Randomization Visit (Visit 2) or received amedical device in another clinical trial within 7 days before the RandomizationVisit (Visit 2), or

2. Any former use of topical capsaicin in the area of the PSNP before Visit 2,except for the use of a low-dose (<1%) capsaicin product - but not within 7days before Visit 2.

3. The subject participated previously in this clinical trial or participated inanother clinical trial for the treatment of PSNP completing less than 3 monthsago.

4. A score of 0 out of 5 in all 3 categories of the neurological/sensory examinations,i.e., for warm sensation, pinprick and cold sensation at the Screening Visit (Visit 1). Confounding factors

5. The subject reported a 24-hr average pain intensity score of 10 on the NPRS for atleast 4 days during the Baseline Phase.

6. Any painful procedure planned during the course of the trial that may, in theopinion of the investigator, affect the efficacy or safety assessments.

7. Subjects with PSNP related to a surgery/condition with a high potential forconfounding symptoms, e.g., the pain is at least partially due to pain in deeperstructures such as muscles or bones (including referred pain from deeper structures)as listed in examples.

8. Other painful conditions in the body area that is affected by PSNP and may affectefficacy or safety assessments and cannot be discriminated from the target pain bythe subject, including infectious, non-infectious, inflammatory or neuropathicconditions which could also be complications related to the previous surgicalprocedure. Non-exhaustive list of examples of types of surgeries/conditions not suitable foreligibility Any surgery performed due to suspected neoplasia: suspected residualneoplasia or metastases Conditions where nociceptive or neuropathic pain has beenthe reason for the surgery, e.g., failed back surgery, carpal tunnel syndrome orother nerve compression syndromes leading to neuropathic pain, (e.g., meralgiaparesthetica) Conditions of projected neuropathic pain (i.e., from inguinal herniarepair) with painful symptoms in the genital region, e.g., the scrotum or vaginaAmputations Radicular pain and nerve trunk lesions Scar pain neuroma ComplexRegional Pain Syndrome (Type I or Type II) Contraindications to IMP

9. Neuropathic pain areas located only on the face, above the hairline of the scalp,and/or in proximity to mucous membranes.

10. Hypersensitivity to capsaicin (i.e., chili peppers or over-the-counter [OTC]capsaicin products), or to any excipients of the IMP or to excipients of thecleansing gel in use and their components, or to topical anesthetics in use andtheir components. Medical history/concurrent condition(s)/other factors

11. Pending litigation due to chronic pain or disability.

12. The subject has a history of alcohol or drug abuse or is actively abusing drugs (including alcohol, medication) during the 1 year prior to the Screening Visit (Visit 1) as judged by the investigator.

13. Evidence or history of severe psychiatric illness/disorder during the 3 years priorto the Screening Visit (Visit 1) that, in the investigator's opinion, may affectefficacy or safety assessments or may compromise the subject's safety during trialparticipation, e.g., major depression, major anxiety disorder, psychosis, severepersonality disorders.

14. Evidence of cognitive impairment including dementia that may interfere with thesubject's ability to complete pain assessments requiring recall of the average painlevel in the past 24 hrs.

15. Surgical intervention in the last 3 months preceding the Screening Visit (Visit 1)if it is affecting the efficacy or safety assessments, or any scheduled or plannedsurgery during the trial, with the exception of the Extension Phase if the plannedsurgery is not expected to affect the efficacy or safety assessments.

16. Patients with current clinically significant disease(s) or condition(s) (includingclinically significant cardiovascular disease and/or significant pain in otherareas) that may affect efficacy or safety assessments, or any other reason which, inthe investigator's opinion, may preclude the subject's participation in the fullduration of the trial. Patients with current signs and symptoms consistent withCoronavirus disease 2019 (COVID-19) (e.g., dry cough, dyspnea, sore throat, fatigue,fever) or patients who had those symptoms within the last 14 days prior to screeningand had a positive SARS-CoV2 PCR test result.

17. Unstable or poorly controlled blood pressure which, in the opinion of theinvestigator, would put the subject at risk of severe adverse blood pressureincreases upon IMP application.

18. Known or suspected of not being able to comply with the requirements of the trialprotocol or the instructions of the trial site staff.

19. Not able to communicate meaningfully with the trial site staff.

20. The subject is an employee of the investigator or trial site, with directinvolvement in the proposed trial or other trials under the direction of thatinvestigator or trial site, or is a family member of the employees or theinvestigator.