A randomized, double-blind, placebo-controlled study to assess the effects of high concentration capsaicin patch (Qutenza) on neuropathic symptoms, nerve fibers, and microcirculation in painful diabetic peripheral neuropathy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Deutsche Diabetes Forschungsgesellschaft e.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2026-01-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Grünenthal GmbH

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the efficacy of repeated treatment with capsaicin 8% cutaneous patch compared to placebo on skin innervation

Secondary objectives 9

1. To evaluate the efficacy of repeated treatment with capsaicin 8% cutaneous patch compared to placebo on cutaneous nerve regeneration
2. To evaluate the efficacy of capsaicin 8% cutaneous patch compared to placebo on neuropathic symptom intensity and sleep interference
3. To evaluate the efficacy of capsaicin 8% cutaneous patch compared to placebo on microcirculation and tissue oxygenation
4. To evaluate the efficacy of capsaicin 8% cutaneous patch compared to placebo on sensory nerve function
5. To evaluate the efficacy of single treatment with capsaicin 8% cutaneous patch compared to placebo on skin innervation
6. To evaluate the effect of capsaicin 8% cutaneous patch compared to placebo on the cutaneous neurovascular network
7. To evaluate the proportion of participants receiving capsaicin 8% cutaneous patch achieving a meaningful intensity reduction in neuropathic symptoms compared to placebo
8. To evaluate the safety and tolerability of capsaicin 8% cutaneous patch compared to placebo, as measured by treatment-emergent adverse events (TEAEs), adverse events (AEs) leading to study discontinuation and serious adverse events (SAEs) throughout the study
9. To evaluate the use of rescue medication for neuropathic pain and the time to first intake of rescue medication following treatment with capsaicin 8% cutaneous patch

Conditions and MedDRA coding

Painful diabetic peripheral neuropathy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Written informed consent signed and dated
2. Diabetes mellitus according to the American Diabetes Association criteria (2017), lasting ≥1 year
3. Age: 18-80 years
4. Presence of painful diabetic sensorimotor polyneuropathy (DSPN) as judged by the investigator lasting ≥6 months
5. Presence of pain in the feet and/or ankle caused by painful DSPN as diagnosed by the investigator with an average or maximum NPRS of ≥4 points within 7 days before screening
6. Presence of dysesthesia or paresthesia in the lower extremity caused by DSPN as diagnosed by the investigator lasting ≥6 months
7. Presence of either i) neuropathic deficits in the lower extremity (reduced or absent achilles tendon reflexes, vibration sensation, temperature detection, pain perception, pressure sensation), ii) ≥1 abnormal nerve conduction study parameter in lower extremity peripheral nerves (reduced or not evoked peroneal or tibial motor nerve conduction velocity or sural sensory nerve conduction velocity or amplitude), iii) ≥1 abnormal quantitative sensory test at the lower extremity (temperature detection threshold, vibration perception threshold), or iv) reduced intraepidermal nerve fiber density at screening
8. HbA1c <10% at screening
9. If applicable, stable regimen of glucose-lowering and analgesic treatment for DSPN within 4 weeks prior to screening as judged by the investigator
10. Willingness to maintain current analgesic treatment unchanged during the course of the study
11. Ability and willingness to meet the study center visits and to undergo study procedures during the whole study duration
12. If applicable, willingness to take acceptable contraceptive measures by female participants in childbearing potential during the treatment phase
13. If applicable, negative urine pregnancy test by female participants in childbearing potential at screening

Exclusion criteria 18

1. Presence of pain caused by other conditions not clearly differentiated from pDPN as judged by the investigator
2. Conditions that might interfere with the assessment of pDPN as judged by the investigator
3. History of foot ulcers within the last 6 months prior to screening
4. History of amputations at the lower extremity excluding minor amputations due to traumatic events not related to diabetic foot syndrome
5. Treatment with Capsaicin 179 mg/8% patch within the last 6 months prior to screening or with any other topical analgesic pain treatment on the areas affected by neuropathic pain due to painful DSPN within the last 3 months prior to screening.
6. Concomitant analgesic treatment for painful DSPN with more than two substances, with medium or high potency opioids, or with electrical stimulation within the last 3 months prior to screening.
7. Substantial change in analgesic treatment regimen during the study as judged by the investigator
8. Contraindications, known allergy, or hypersensitivity to capsaicin or other ingredients of the study medication or local anesthetics
9. Average daily pain level ≥9 points NPRS within 7 days before screening
10. Intraepidermal nerve fiber density at screening <1 fiber/mm
11. Treatment with coumarins or heparin in a therapeutic dose or other contraindications against obtaining skin biopsies at the distal calf
12. Pregnant women or nursing mothers
13. Participation in another clinical trial study within the last 3 months prior to screening
14. Neoplasms, except for basal cell carcinoma (basalioma) or low-grade prostate cancer within 12 months prior to screening
15. Currently active or history of alcohol use disorder (>24 units of alcohol per week) or other substance-use disorders as judged by the investigator within the last 5 years
16. Uncontrolled high blood pressure (DBP >95 mmHg and/or SBP >160 mmHg), unless clearly documented to be white-coat hypertension, at screening
17. Severe resting tachycardia (HR >110 bpm) at screening
18. Mental, psychiatric or other conditions compromising data collection or understanding of written or oral instructions during the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from Baseline in IENFD (PGP9.5) at site with repeated treatment at Week 35 compared to placebo (primary endpoint)

Secondary endpoints 9

1. Change from Baseline in IENFD (GAP-43), IENFL and DNFL (PGP9.5, GAP-43) at site with repeated treatment at Week 35 compared to placebo
2. Change from Baseline in NPRS, PDQ7, NPSI, TSS, NSS, and MOS-12 at Week 11, Week 25, and Week 35 compared to placebo
3. Change from Baseline in LDF and tissue oxygenation at standard and treated sites at Week 11 and Week 35 compared to placebo
4. Change from Baseline in QST and monofilament at standard and treated sites at Week 11 and Week 35 compared to placebo
5. Change from Baseline in IENFD, IENFL and DNFL (PGP9.5, GAP-43) at Week 11 and Week 35 (at site with single treatment only) compared to placebo
6. Change from Baseline and from Week 10 in skin biopsy CD31 area and CD31-PGP9.5 at sites with single and repeated treatment at Week 35 compared to placebo
7. Proportion of participants with an improvement in NPRS, PDQ7, NPSI, TSS, and NSS items reflecting the intensity of general pain, burning pain, pressing pain, paroxysmal pain, evoked pain, dysesthesia, and paresthesia, if present at baseline, compared to placebo at end of study
8. Number and severity of treatment-emergent AEs and the frequency of AEs leading to discontinuation, number of SAEs compared to placebo
9. Proportion of participants who need rescue medication, frequency and amount of rescue medication, and time to first intake of rescue medication since randomization compared to placebo

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Deutsche Diabetes Forschungsgesellschaft e.V.

Sponsor organisation

Deutsche Diabetes Forschungsgesellschaft e.V.

Address

Auf'm Hennekamp 65, Bilk Bilk

City

Duesseldorf

Postcode

40225

Country

Germany

Scientific contact point

Organisation

Deutsche Diabetes Forschungsgesellschaft e.V.

Contact name

Gidon Bönhof

Public contact point

Organisation

Deutsche Diabetes Forschungsgesellschaft e.V.

Contact name

JRG Neuropathy

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications