EASE (Efficacy of ATX01 Study in Erythromelalgia)

Exclusion Criteria

• •1. Clinical evidence of a pre-existing pain disorder in the extremities resulting from another cause than erythromelalgia, e.g. complex regional pain syndrome (CRPS), diabetic neuropathy, chemotherapy-induced peripheral neuropathy (CIPN).
• •2. Evidence of skin breakdown, ulcers, papules and \> +2 pitting edema of the affected limbs.
• •3. Presence of glaucoma.
• •4. Presence of urinary retention (or significant prostatic hypertrophy at risk of urinary retention).
• •5. History of coronary artery disease.
• •6. History and /or presence of major depressive episode.
• •7. The patient has suicidal risk in the opinion of the investigator based upon clinical interview and the Columbia Suicide-Severity Rating Scale.
• •8. Pregnant or lactating women.
• •9. Abnormality in the 12-lead electrocardiogram (ECG) at screening that in the opinion of the investigator increases the risk of participating in the study, such as a corrected QT Fridericia (QTcF) interval \>430 ms for males or \>450 ms for females.
• •10. A history of additional risk factors for Torsade de Pointe (e.g. heart failure, hypokalemia, family history of Long QT Syndrome).
• •11. The use of concomitant medications within 24 weeks prior to Day 1 and/or during the study or the equivalent of 5 half-lives that prolong the QT/QTc interval, eg, Class 1 antiarrhythmics (e.g. quinidine, disopyramide, procainamide) and Class 3 antiarrhythmics (e.g. amiodarone, sotalol), antihistamines, antipsychotics known to prolong QT interval, and antimalarials (e.g. mefloquine, quinine), tricyclic antidepressants (e.g. AMT), tetracyclic antidepressants (e.g. maprotiline), cisapride.
• •12. The use of monoamine oxidase inhibitors within 24 weeks (or the equivalent of 5 half-lives) prior to Day 1 and/or during the study.
• •13. The use of opioids within 4 weeks (or the equivalent of 5 half-lives) prior to Day 1 and/or during the study.
• •14. History of illicit drug use or confirmed drugs of abuse at screening. Positive urine drug screen for prescribed medication is allowed at the discretion of the investigator.
• •15. Use of more than 2 analgesics (regardless of the route of administration) from different drug classes (including antidepressants and antiepileptics) on top of study drug.
• •16. Treatment with oral or topical amitriptyline or nortriptyline in the past 4 weeks or current treatment with any other tricyclic antidepressant.
• •17. Any known hypersensitivity to amitriptyline (regardless of the route of administration) in any salt form or to any constituent of the topical formulation.
• •18. Use of glutathione, vitamin E, minocycline, or calcium magnesium supplements within 12 weeks of screening.
• •19. Any topical treatment on treated extremities for any indication, other than cosmetic use of creams and lotions, within the 12 weeks prior to screening.
• •20. Any topical treatment for pain including use of:
• •1. over-the-counter capsaicin on extremities within 12 weeks of screening,
• •2. and/or Qutenza within 24 weeks of screening,
• •3. and/or nonsteroidal anti-inflammatory drugs, menthol, methyl salicylate, local anesthetics within 1 week of screening.
• •21. Implanted active medical device (eg, spinal cord stimulator, intrathecal pump, or peripheral nerve stimulator) for the treatment of pain or any etiology.
• •22. Regional anesthetic block for pain of any etiology within 3 months prior to screening.
• •23. Intake in the 4 weeks preceding screening visit of any medication susceptible to inhibit or induce cytochrome P450 CYP2D6.
• •24. Poor metabolizers of CYP2D6 substrates.
• •25. Treatment with an investigational drug in the previous 4 weeks or greater, according to local requirements
• •26. Any condition that the investigator feels would place the patient at increased risk if the investigational therapy is initiated, such as, but not limited to, hyperthyroidism, convulsive disorder, advanced hepatic disease, pylorus, stenosis, or paralytic ileus.
• •27. The investigator considers the patient unfit for the study as a result of the medical interview, physical examination, or screening investigations, in particular any status or disease making the patient unable to follow instructions.
• •28. The patient is unable to apply the study drug on feet and/or hands.
• •29. The patient is an employee of the investigator, study site, sponsor, or contract research organization with direct involvement in the proposed study or other studies under the direction of the investigator, study site, or sponsor, or a family member of the site employee or the Investigator.