A 16-Week Study of Pirenzepine or Placebo to Treat HIV-Associated Distal Sensory Polyneuropathy in Patients With HIV

Exclusion Criteria

• •1. Current intoxication (BAC \> 0.08%) at the screening visit at the discretion of the investigator (breathalyzer analysis).
• •2. Neuropathy due to exposure to current use/ chemotherapeutic agents or other neurotoxins; at the discretion of the investigator.
• •3. Individuals with the onset of Type 2 diabetes mellitus before HIV infection.
• •4. Uncontrolled or Insulin-dependent diabetes mellitus.
• •5. Proliferative retinopathy or maculopathy requiring acute treatment.
• •6. Requiring dialysis. Impaired liver function, defined as aspartate aminotransferase or alanineaminotransferase \> 3 times the upper limit of normal.
• •7. Presence of clinically significant peripheral or autonomic neuropathy that is clearly of non HIVN origin.
• •8. Active and/or systemic infections with hepatitis C (as per investigator judgement following serology results) or syphilis, or a history of severe infection during the 30 days prior to screening.
• •9. Diagnosis and/or treatment of malignancy (except for basal cell or squamous cell skin cancer, in-situ carcinoma of the cervix, or in-situ prostate cancer) within the past 5 years.
• •10. Clinically significant diagnosed gastric emptying abnormality (e.g., severe gastroparesis).
• •11. Clinically significant - urinary retention confirmed by bladder ultrasound regardless of etiology.
• •12. Uncontrolled glaucoma.
• •13. Other clinically significant, active (over the past 12 months) disease of the cardiovascular, gastrointestinal, pulmonary, neurological, genitourinary, endocrine, rheumatologic or hematological system that, in the opinion of the Investigator, would compromise the subject's participation in the study, might confound the results of the study, or pose additional risk in administering the study drug.unstable/untreated clinically significant.
• •14. New treatment with (\< 2 months) antioxidant supplements, vitamins, or drugs known to affect oxidative stress and such as Superoxide Dismutase, Alpha Lipoic Acid, Acetyl L-Carnitine and Vitamin B12.
• •15. Mental incapacity, unwillingness, or language barrier precluding adequate understanding of or cooperation with the study.
• •16. Women of childbearing potential who are pregnant, breast-feeding, or intend to become pregnant. Women of childbearing potential must have a negative pregnancy test at Screening and must agree to use adequate contraceptive methods during the study and for 1 month after the last dose of study drug (see inclusion criterion 5).
• •17. History of allergy or sensitivity to M1 antagonists or anticholinergics in general or any of the components of the investigational product formulations.
• •18. Local (topical) anesthetics or analgesics including lidocaine, capsaicin, cannabinoid (CBD) oil/products or compounded topical pharmaceutical agents.
• •19. Uncontrolled treated/untreated hypertension (systolic blood pressure \[BP\] \> 180 or diastolic BP \> 100 at screening).
• •20. Amputations of lower extremities or presence of foot ulcers.
• •21. Clinically significant active macrovascular disease, including myocardial infarction, arrythmias, prolonged QT syndrome, or cerebrovascular event within the past 6 months.
• •22. A history of severe infection during the 30 days prior to screening.
• •23. Major surgical procedure during the 90 days prior to screening.
• •24. History of sensitive skin, as defined by a requirement to use soap and skin products formulated for "sensitive skin," as determined by the Investigator.
• •25. Currently taking M1 antagonists medicines to treat overactive bladder (anticholinergic agents, such as Gelnique), or antispasmodics.
• •26. Failure or inability to perform screening or baseline assessments.
• •Patients with any condition that could potentially interfere with the conduct of the study or confound efficacy evaluations, including the following as specified in numbers 26 through 32 below:
• •27. Pain or neuropathy from another cause, as determined by the investigator (including central pain, radiculopathy, painful arthritis, etc.).
• •28. Active skin or soft-tissue lesions in the dosing area (calves, ankles and tops of feet) affected by neuropathy that are painful or could alter sensation.
• •29. Exposure to an experimental drug, experimental biologic, or experimental medical device within 3 months before screening.
• •30. Any open wound(s) and/or sunburn(s) in the dosing area. Subjects who have a wound and/or sunburn at screening that is anticipated to resolve before day -1 can be enrolled.
• •31. History of a serious skin disease (as determined by the Investigator), such as skin cancer, psoriasis, stasis dermatitis or eczema.
• •32. Receipt of a tattoo in the dosing area within 12 months of dosing.
• •33. Known or untreated Lyme disease.