Theophylline Nasal Spray for PD-Related Hyposmia and Anosmia

Prior treatment

• Concomitant Medical Conditions:
  • Current symptoms or signs of acute respiratory viral illness at Screening or Baseline.
  • Any acute upper respiratory tract infection or allergy that has acutely changed the participant's sense of smell at Screening or Baseline.
  • Any nasal bleeding, crusting or other process that would impair ability to perform smell test.
  • Chronic viral infection or immunodeficiency condition (e.g., medical history of human immunodeficiency virus) based on medical records.
  • Any active malignancy.
  • Any concomitant medical condition that in the opinion of the Investigator, compromises patient safety or compliance with the study protocol or collected data.
• Use or planned use of THC-containing products, tobacco, or nicotine-containing products, including smoking, smokeless tobacco, e-cigarettes, vapes, or nicotine replacement products within 3 months prior to Screening through end of study.
• Usage of Medications:
  • History of an allergic reaction to theophylline or other methylxanthines.
  • Unwilling or unable to discontinue current or planned use of over the counter (OTC) or prescription medication administered intranasally, including non-nasal indications such as bisphosphonates for osteoporosis, etc., with the exception of nasal saline.
  • Current, recent (within 30 days prior to Screening), or planned (from Screening through Follow-Up) use of theophylline for any reason other than the planned study drug.
  • Use or planned use of another investigational drug within 4 weeks prior to Screening through Follow-Up.
  • Receiving any concomitant medication/therapy that would, in the opinion of the Investigator, compromise participant safety or compliance with the study protocol or collected data.
• Concomitant procedures:
  • Planned nasal procedures within 90 days prior to screening and throughout study through follow-up.
  • Planned surgical procedure during study participation that would interfere with the participant's ability to perform study procedures.
  • Olfactory training must be discontinued 30 days prior to baseline through follow-up.

Other illness

• Hyposmia due to other causes (non-Parkinson's Disease related):
  • History of traumatic brain injury, viral related smell loss or any other condition in which hyposmia is not expected to improve in the opinion of the Investigator, such as history of congenital or idiopathic hyposmia or a surgical procedure that led to hyposmia.
  • History of systemic conditions or structural abnormalities known to impact the sinonasal cavity (e.g., granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, severe septal deviation, nasal polyposis, intranasal mass, or tumor) that would impact delivery of drug.
  • History of anosmia or hyposmia due to nasal polyps.
  • History of surgery that led to hyposmia.
• History of Substance Use Disorder of moderate or greater severity within the past 3 years as assessed by the Investigator.
• History of persistent chronic sinusitis without polyps or chronic sinusitis with polyps.
• Participants with visible signs of, and/or active symptoms of chronic sinusitis or respiratory infection at Screening or Day 1/Baseline.
• Severe allergic rhinitis requiring intranasal medications.

Lab values

• General Exclusions:
  • Female who is pregnant, planning to become pregnant during the study, or who is lactating.
  • Any condition or abnormality (including clinical laboratory, physical examination, or vital sign abnormalities), current or past, that, in the opinion of the Investigator, would compromise the efficacy evaluation, safety of the patient, or would interfere with or complicate study procedures or assessments.

Other

• Participants whose primary complaint elated to olfactory dysfunction, in the opinion of the Investigator, is parosmia.

• Able to provide written informed consent.
• 19-80 years of age.
• Subjective or clinically diagnosed hyposmia/anosmia > 6 months with onset related to Parkinson's Disease. Note: participants may be rescreened at a later time if duration of hyposmia is determined to be < 6 months.
• Hyposmia defined as ≤5 on the NRS-11 Smell-PRO smell scale (scale of 0-10; 10 indicating normal sense of smell, 0 indicating no sense of smell).
• Hoehn and Yahr scale is <3.
• Montreal Cognitive Assessment (MOCA) score >24.
• Endoscopy of the nasal cavity showing no structural or pathologic issues leading to hyposmia (nasal polyps, sinusitis, infection, etc.) that in the opinion of the Investigator, believes would hinder the delivery of study drug to the olfactory region of the nasal cavity.
• Willing and able to self-administer the study drug, follow the study drug administration instructions, comply with study procedures, and participate in the scheduled study visits specified in this protocol.
• Score Sniffin Sticks Olfactory Test Threshold, Discrimination and Identification (TDI) at baseline and EOS.