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HyposmiaPhase 1NCT06498687

Theophylline Nasal Spray for PD-Related Hyposmia and Anosmia

A Phase 1 study testing CYR-064 in people with Hyposmia and Anosmia, run by University of Nebraska.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 19 to 80 years
Conditions the study is for
Hyposmia, Anosmia
What is being tested?
CYR-064
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Apr 2025to Jul 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 9Show fewer
  • 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.

Who cannot join

  • 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.
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  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

About this study

Official title: A Single-Arm Study to Evaluate the Feasibility of CYR-064 Theophylline Nasal Spray for the Treatment of Parkinson's Disease Related Hyposmia and Anosmia

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.

Read the detailed description

This is a single-arm study that will investigate the use of intranasal theophylline (CYR-064) for the treatment of hyposmia and anosmia related to the onset of Parkinson's disease. The study drug of CYR-064, self-administered for a 24-week Treatment Period, is intended to improve the sense of smell in participants with persistent hyposmia and anosmia related to the onset of Parkinson's Disease. The study population will include approximately 15 adult participants between the ages of 19 to 80 years with moderate to severe hyposmia or anosmia caused by the onset of Parkinson's Disease. Eligible participants who meet all study criteria and have consented to participation will receive the investigational new drug (CYR-064) with a dose strength of 1120ug/day administered for 24 weeks. During the 24-week Treatment Period, participants will be asked to complete a weekly paper Diary with two questions to monitor compliance to the study drug.

Participants will be prompted and instructed to provide responses to 11-point Numeric Rating Scale (NRS-11) smell and taste symptom assessments on a scale of 0-10 (10 indicating normal senses), starting with the baseline visit and then weekly throughout the duration of the study via paper diary. Participants will return to the clinic every 2 weeks for the first month of the Treatment Period, followed by monthly in-clinic visits thereafter for the assessment of safety and efficacy of CYR-064 at 8, 12, 16 and 24 weeks.

At baseline and week 24, patients will be given the Sniffin Sticks threshold, discrimination, and identification (TDI) test.

At baseline and week 24, patients will be given the global impression of smell loss severity (PGI-SLS), smell loss change (PGI-SLC), global impression of loss of ability to taste food (PGI-TS), and change in ability to taste food (PGI-TC) questions. (note: each of these constitutes one multiple choice question).

At baseline and week 24, patients will be given the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) parts I and III, the Craft Story Recall, the Benson Complex Figure Test, and the Hopkins Verbal Learning Test - Revised.

All participants will have intra-nasal examination and nasal endoscopy performed at baseline and at 24 weeks to ensure no structural or pathological issues are present leading to hyposmia and for assessment of safety. Adverse events (AE) will be assessed through clinical symptom presentation, intra-nasal examination, and endoscopy.

At each monthly in-clinic visit, participants will return the vials with the study drug (full or empty) and receive new vials for use during the following study period. Week 24/end of study (EOS) will serve as the last visit for all patients who complete the study, followed by a 30-day follow-up. Participants who discontinue treatment or study at any time will return to the clinic for the EOS visit. At Week 28 (± 7 days), a follow-up phone call to assess final safety and efficacy will conclude the participant's participation in the study.

Conditions
Hyposmia, Anosmia
Being tested
CYR-064
Keywords
Parkinson's Disease, Anosmia, hyposmia, Intranasal, Theophylline, Feasibility
Medical subject headings
Anosmia, Parkinson Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CYR-064Drug

    Also called Theyophylline

    Theophylline Nasal Spray

Study groups in NCT06498687
Study groupRoleWhat they receive
Intranasal TheophyllineExperimentalTheophylline 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.
Receives: Drug: CYR-064

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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"

    Measured: baseline to week 24

  2. 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"

    Measured: baseline to week 24

  3. 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"

    Measured: baseline to week 24

  4. 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"

    Measured: baseline to week 24

Secondary outcomes (3)
  1. Cumulative Adverse Events (AEs)

    Cumulative adverse events related to CYR-064

    Measured: baseline to week 24

  2. Cumulative Serious Adverse Events (SAEs)

    Cumulative serious adverse events related to CYR-064

    Measured: baseline to week 24

  3. Cumulative Suspected, Unexpected, Serious Adverse Events Related (SUSARs)

    Cumulative Suspected, Unexpected, Serious Adverse Events Related to CYR-064

    Measured: baseline to week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jul 2024
  2. Study startApr 2025 (estimated)
  3. Primary completionJun 2026 (estimated)
  4. Study completionJul 2026 (estimated)

Why it stopped: sponsor discontinued site participation

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06498687
Sponsor's protocol ID
0527-24-FB
Status last verified
Mar 2025
First submitted
5 Jul 2024
Last updated
13 Mar 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • CDC.gov. Weekly U.S. Influenza Surveillance Report. https://www.cdc.gov/flu/weekly/index.htm. Updated 29 April 2022. Accessed 04 May 2022.

  • Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases (NCIRD). 2021-2022 U.S. Flu Season: Preliminary In-Season Burden Estimates. https://www.cdc.gov/flu/about/burden/preliminary-in-season-estimates.htm. Updated 29 April 2022. Accessed 04 May 2022.

  • Choi JS, Jang SS, Kim J, Hur K, Ference E, Wrobel B. Association Between Olfactory Dysfunction and Mortality in US Adults. JAMA Otolaryngol Head Neck Surg. 2021 Jan 1;147(1):49-55. doi: 10.1001/jamaoto.2020.3502.

    PubMed 33090196
  • Ciurleo R, De Salvo S, Bonanno L, Marino S, Bramanti P, Caminiti F. Parosmia and Neurological Disorders: A Neglected Association. Front Neurol. 2020 Nov 9;11:543275. doi: 10.3389/fneur.2020.543275. eCollection 2020.

    PubMed 33240192
  • Coelho DH, Reiter ER, French E, Costanzo RM. Decreasing Incidence of Chemosensory Changes by COVID-19 Variant. Otolaryngol Head Neck Surg. 2023 Apr;168(4):704-706. doi: 10.1177/01945998221097656. Epub 2023 Feb 5.

    PubMed 35503739
  • Croy I, Symmank A, Schellong J, Hummel C, Gerber J, Joraschky P, Hummel T. Olfaction as a marker for depression in humans. J Affect Disord. 2014 May;160:80-6. doi: 10.1016/j.jad.2013.12.026. Epub 2014 Jan 4.

    PubMed 24445134
  • Dai Q, Pang Z, Yu H. Recovery of Olfactory Function in Postviral Olfactory Dysfunction Patients after Acupuncture Treatment. Evid Based Complement Alternat Med. 2016;2016:4986034. doi: 10.1155/2016/4986034. Epub 2016 Feb 29.

    PubMed 27034689
  • FDA-4927905. FDA PIND Written Response Only (WRO) Meeting. 27 January 2022.

  • FDA Guidance for industry COVID-19: Developing Drugs and Biological Products for Treatment or Prevention Guidance for Industry. 2021. Available from: https://www.fda.gov/media/137926/download.

  • Amai M, Nojima M, Yuki Y, Kiyono H, Nagamura F. A review of criteria strictness in "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials". Vaccine. 2023 Aug 31;41(38):5622-5629. doi: 10.1016/j.vaccine.2023.07.072. Epub 2023 Aug 1.

    PubMed 37532612
  • Fonteyn S, Huart C, Deggouj N, Collet S, Eloy P, Rombaux P. Non-sinonasal-related olfactory dysfunction: A cohort of 496 patients. Eur Ann Otorhinolaryngol Head Neck Dis. 2014 Apr;131(2):87-91. doi: 10.1016/j.anorl.2013.03.006. Epub 2014 Mar 26.

    PubMed 24679542
  • Harless L, Liang J. Pharmacologic treatment for postviral olfactory dysfunction: a systematic review. Int Forum Allergy Rhinol. 2016 Jul;6(7):760-7. doi: 10.1002/alr.21727. Epub 2016 Feb 16.

    PubMed 26879592
  • Hendeles L, Bighley L, Richardson RH, Hepler CD, Carmichael J. Frequent toxicity from IV aminophylline infusions in critically ill patients. 1977. Ann Pharmacother. 2006 Jul-Aug;40(7-8):1417-23. doi: 10.1345/aph.140027. No abstract available.

    PubMed 16868215
  • Henkin RI, Levy LM, Fordyce A. Taste and smell function in chronic disease: a review of clinical and biochemical evaluations of taste and smell dysfunction in over 5000 patients at The Taste and Smell Clinic in Washington, DC. Am J Otolaryngol. 2013 Sep-Oct;34(5):477-89. doi: 10.1016/j.amjoto.2013.04.006. Epub 2013 Jun 2.

    PubMed 23731850
  • Henkin RI. Comparative monitoring of oral theophylline treatment in blood serum, saliva, and nasal mucus. Ther Drug Monit. 2012 Apr;34(2):217-21. doi: 10.1097/FTD.0b013e3182492a20.

    PubMed 22377744

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CYR-064 in people with Hyposmia and Anosmia, run by University of Nebraska.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 13 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Numeric Rating Scale-11 Smell-Patient Reported Outcome (PRO) (NRS-11-PRO): Improvement (time frame: baseline to week 24). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06498687, which also lists 46 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2025.

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