Safety and Efficacy of FSD202 for the treatment of chronic pain associated with idiopathic MCAS (MCAD)

Exclusion Criteria25

• The participant has pain that cannot be clearly differentiated from or that could interfere with the assessment of chronic musculoskeletal nociplastic pain secondary likely to idiopathic MCAS (e.g., post-herpetic neuralgia, traumatic injury, prior surgery, complex regional pain syndrome)
• Adults with chronic cancer pain
• Adults with inflammatory connective tissue disorder or rheumatological disorder-related pain (e.g., rheumatoid arthritis)
• Adults with focal musculoskeletal pain
• Adults with skin diseases (e.g., pemphigus vulgaris, bullous pemphigoid, etc.) that, in the judgment of the investigator, could interfere with reporting of pain due to chronic widespread musculoskeletal nociplastic pains
• Adults with acute endocrinological disorders (e.g., acute hypothyroidism, acute adrenal insufficiency etc.)
• Adults with systemic gastrointestinal conditions (e.g., Inflammatory bowel disease)
• Significant psychological comorbidities: PHQ-9 score more than 20; and GAD-7 score more than 15 (indication of severe anxiety that could interfere with accurate logging of pain ratings)
• Current or recent (within 12 months of screening) history of a substance use disorder including cannabinoid or alcohol use disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders (5th edition; DSM-5)
• Participant has neurologic disorder unrelated to chronic widespread musculoskeletal nociplastic pains (e.g., phantom limb from amputation, vitamin B12 deficiency, chronic inflammatory demyelinating polyneuropathy), circulatory disorder (e.g., peripheral artery disease), a skin condition in the area of neuropathy that could alter sensation (e.g., plantar ulcer), or other painful conditions (e.g., arthritis) that, in the judgment of the investigator, could interfere with reporting of pain due to chronic widespread musculoskeletal nociplastic pains
• Current severe or uncontrolled major depressive disorder or anxiety disorders. Mild to moderate major depression or anxiety disorders are permitted provided that the investigator assesses the participant as clinically stable and appropriate for entry into the study. Stable doses of the selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) are allowed for the treatment of depression if the dose is stable for 60 days before Screening Visit
• Participant has a history of suicide attempt or suicidal behavior within the last 12 months or has suicidal ideation within the previous 12 months or who is at significant risk to commit suicide, as judged by the Investigator at Screening or during the treatment period
• The participant is currently using protocol-specified prohibited medications
• Positive urine drug screen for illegal or non-prescribed drugs (with the exception of benzodiazepines and cannabinoids) at the Screening Visit or during the treatment period.
• Pregnant or lactating females or females planning to become pregnant during the study or within 28 days following the last dose of study medication.
• Male participants planning a partner pregnancy or sperm donation during the study or within three months following the last dose of study medication.
• Participants with active malignancy or history of malignancy, except for basal cell or squamous cell carcinoma and actinic keratosis. Basal cell carcinoma and small squamous cell carcinoma of the skin which have been excised according to guidelines within the last 5 years or in situ cervical carcinoma that has been fully treated and shows no evidence of recurrence are allowed.
• Positive human immunodeficiency virus (HIV), hepatitis B or hepatitis C laboratory result.
• Any clinically significant unstable medical abnormality or acute or chronic disease of the cardiovascular, gastrointestinal, respiratory, hepatic, or renal systems. Participant with aspartate transferase or alanine transferase more than 2.5 times the upper limit of normal (ULN) or alkaline phosphatase more than 3.0 times ULN.
• Any clinically significant deviation from normal in physical examination, vital signs, or clinical laboratory tests, as determined by the investigator.
• Known history of seizure disorder, epilepsy, convulsions, or increased intracranial pressure anytime during the participant's life except for pediatric febrile seizures.
• Participant has received an investigational therapy of any kind within 28 days or 5 half-lives, whichever is longer, before Screening Visit.
• Participant has had known hypersensitivity or intolerance to the use of Palmitoylethanolamide (PEA), diphenhydramine (e.g. Benadryl) or acetaminophen (e.g. Tylenol) and/or their associated formulation components
• The participant is a member of the site staff or relative of a staff member
• Individuals with high baseline serum tryptase levels (defined as above the normal range of 2.2 to 13.2 µg/L) suggestive of Primary or Secondary MCAS