E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Peripheral neuropathic pain with sensory hypersensitivity |
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E.1.1.1 | Medical condition in easily understood language |
Peripheral neuropathic pain with sensory hypersensitivity |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10077974 |
E.1.2 | Term | Peripheral neuropathic pain |
E.1.2 | System Organ Class | 100000004852 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this clinical study is to investigate whether the gel ACD440 (14 mg/g) can reduce evoked pain compared to placebo in subjects with peripheral neuropathic pain with sensory hypersensitivity. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the effect of ACD440 on average pain intensity. 2. To evaluate subject perceived overall treatment effect. 3. To evaluate an effect of ACD440 on spontaneous burning pain. 4. To evaluate an effect of ACD440 on spontaneous pressing pain. 5. To evaluate an effect of ACD440 on paroxysmal pain. 6. To evaluate an effect of ACD440 on overall evoked pain. 7. To evaluate an effect of ACD440 on paresthesia/dysesthesia. 8. To evaluate an effect of ACD440 on duration of spontaneous pain. 9. To evaluate an effect of ACD440 on frequency of pain attacks. 10. To evaluate an effect of ACD440 on Neurotic Pain Symptom Inventory (NPSI) total score
Safety objective: The safety objective is to evaluate the safety and tolerability of ACD440 in subjects with peripheral neuropathic pain with sensory hypersensitivity.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent prior to any study related procedures. 2. Male or female between 18 and 85 years of age, inclusive, at the screening visit. 3. Diagnosed with painful peripheral polyneuropathy (PNP), including etiologies behind the PNP being but not limited to painful peripheral polyneuropathy, peripheral mononeuropathy, postherpetic neuralgia (PHN), chemotherapy induced neuropathic pain, nerve injury pain, chronic postoperative neuropathic pain with a history of 6 months to 10 years prior to the screening visit. 4. Hypersensitivity to one or more of the following sensory stimuli: mechanical (brush or pinprick), thermal (cold). 5. Pain intensity of 4-7 out of 10 on the Numerical Rating Scale (NRS) to any of the sensory stimuli mentioned in inclusion criterion 4. The area of sensory hypersensitivity can be up to a total of 600 cm2. 6. Subjects with reproductive potential will need to use accepted and highly effective means of contraception from study entry until at least 6 weeks for females (women of childbearing potential, WOCP) and 3 months for males after IMP discontinuation (as per the Clinical Trials Facilitation and Coordination Group (CTFG) guidelines).
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E.4 | Principal exclusion criteria |
1. Participated in a clinical study and received active drug in such a study within 30 days or 5 study drug half-lives, whichever the longest, prior to screening visit. 2. A body mass index (BMI) <18.5 kg/m2 or >35 kg/m2. 3. Serum aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) levels >2 times the upper limit of normal (ULN) at the screening assessments. 4. Evidence and/or history of any clinically significant neurological disease, other systemic diseases or conditions potentially interfering with study assessments, as judged by the investigator. 5. Have another concomitant pain condition with an intensity of ≥4 out of 10, for which, as judged by the principal investigator, pain ratings may interfere with study assessments. 6. Have a Hospital Anxiety and Depression Scale (HADS) score of 15 or above. 7. Active Human immunodeficiency virus (HIV) or ongoing hepatitis B and/or C. 8. Ongoing infection with fever (i.e., body temperature >38.0°C). 9. Known history of hypersensitivity to IMP components or a history of anaphylactic reactions. 10. Malignancy within the past 3 years. In situ basal cell carcinoma and in situ squamous cell carcinoma of the skin are exempt, unless localised to the area of neuropathic pain. 11. History of dermatological diseases including rosacea, syphilitic and tuberculotic reactions. 12. Open wounds, scars, as well as extended tattoos on intended treatment areas. 13. Skin infections, acne, skin inflammation, eczema, or other dermatological disorders in the intended treatment area. 14. Pregnant or breastfeeding female or female who is planning pregnancy during the study period. 15. Could be negatively affected by participation in the study, as judged by the investigator. 16. Diagnosed with any significant psychiatric disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM) 5® criteria, including drug abuse or dependency. 17. Daily intake of opioids at a daily dose of more than 60 morphine equivalents. 18. Use of Lidocaine patches within 7 days prior to randomisation until the follow-up visit. 19. Use of Capsaicin patches within 4 months prior to randomisation until the follow-up visit. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy endpoint(s): Change from baseline in evoked pain defined as: Change from baseline in evoked brushing pain score, evoked pressure pain score or evoked cold pain score: the one of the three items for which the subject scores highest at baseline. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 7 of each treatment period |
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E.5.2 | Secondary end point(s) |
1. Change from baseline in average pain intensity score. 2. Patient’s global impression of change. 3. Change from baseline in spontaneous burning pain subscore. 4. Change from baseline in spontaneous pressing pain subscore. 5. Change from baseline in paroxysmal pain subscore. 6. Change from baseline in evoked pain subscore. 7. Change from baseline in paresthesia/dysesthesia subscore. 8. Change from baseline in duration of spontaneous pain in the past 24h. 9. Change from baseline in number of pain attacks in the past 24h. 10. Change from baseline in NPSI total score.
Safety endpoints: Collection of adverse events (AEs), including: - Spontaneous reporting - Changes from baseline in clinical safety laboratory blood and urine test values and vital signs AEs of special interest
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary efficacy endpoint(s) and safety endpoints: Day 7 of each treatment period
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
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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 | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 9 |