Theophylline Nasal Spray for PD-Related Hyposmia and Anosmia

NCT06498687 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: 0527-24-FB
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this study is to learn if intranasal theophylline (CYR-064) improves sense of smell in participants with hyposmia or anosmia related to the onset of Parkinson's Disease. Fifteen adults, age 19-80, years will participate for about 32 weeks. They will use the study nasal spray for 24 weeks. The nasal spray is given as 2 sprays to each side of the nose twice per day. They will be seen every 2 weeks during the first month of treatment, followed by monthly in-person visits. Tests about memory, Parkinson's Disease symptoms, and ability to detect and identify smells will be completed. Participants are monitored for any side effects.

Conditions

Hyposmia; Anosmia

Keywords

Parkinson's Disease; Anosmia; hyposmia; Intranasal; Theophylline; Feasibility

Outcome Measures

Primary Outcomes (4)

• Numeric Rating Scale-11 Smell-Patient Reported Outcome (PRO) (NRS-11-PRO): Improvement

  Improvement in patient-reported paper diary (scale 0-10). Score of 0="I cannot smell anything", to 10="My sense of smell is normal to me"

  baseline to week 24

• Numeric Rating Scale-11 Taste-Patient Reported Outcome (PRO) (NRS-11-PRO): Improvement

  Improvement in patient-reported paper diary (scale 0-10). Score of 0="I could not taste food", to 10="My food tastes normal to me"

  baseline to week 24

• Numeric Rating Scale-11 Smell-Patient Reported Outcome (PRO) (NRS-11-PRO): Mean Change

  Mean Change in patient-reported paper diary (scale 0-10) of sense of smell. Score of 0="I cannot smell anything", to 10="My sense of smell is normal to me"

  baseline to week 24

• Numeric Rating Scale-11 Taste-Patient Reported Outcome (PRO) (NRS-11-PRO): Mean Change

  Mean Change in patient-reported paper diary (scale 0-10) of ability to taste food. Score of 0="I could not taste food", to 10="My food tastes normal to me"

  baseline to week 24

Secondary Outcomes (3)

• Cumulative Adverse Events (AEs)

  baseline to week 24

• Cumulative Serious Adverse Events (SAEs)

  baseline to week 24

• Cumulative Suspected, Unexpected, Serious Adverse Events Related (SUSARs)

  baseline to week 24

Other Outcomes (8)

• Change in Sniffin' Sticks Threshold, Detection and Identification (TDI) Scores

  baseline to week 24

• Mean Change in Sniffin' Sticks Threshold, Detection and Identification (TDI) Scores

  baseline to week 24

• Numeric Rating Scale-11 Smell-Patient Reported Outcome (PRO) (NRS-11 Smell Impact-PRO Score)

  baseline to week 24

Study Arms (1)

Intranasal Theophylline

EXPERIMENTAL

Theophylline Intranasal Spray strength 3.1mg/mL, providing a per spray dose of 140 microgram and total daily dose of 1120 microgram per day (2 sprays per naris BID). Intervention is self-administered.

Drug: CYR-064

Interventions

CYR-064 DRUG

Theophylline Nasal Spray

Also known as: Theyophylline

Intranasal Theophylline

Eligibility Criteria

• Age: 19 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide written informed consent.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• University of Nebraska: lead

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MeSH Terms

Conditions

Anosmia; Parkinson Disease

Condition Hierarchy (Ancestors)

Olfaction Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Mara Seier, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2024
• First Posted: July 12, 2024
• Study Start: April 1, 2025
• Primary Completion: June 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: March 13, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share