CYR-064 for Loss of Smell

Recruiting at 14 trial locations

Overseen By Mas Takashima, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Cyrano Therapeutics, Inc.

Must not be taking: Intranasal medications

Disqualifiers: Brain injury, Parkinson's, Alzheimer's, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

150 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to stop using any over-the-counter or prescription medications administered intranasally, except for nasal saline. Other medications may need to be stopped if the investigator believes they could affect safety or compliance with the study.

What data supports the effectiveness of the drug CYR-064 for loss of smell?

Research shows that theophylline, a component of CYR-064, improved smell function in over 50% of patients with smell loss (hyposmia) in several studies. This suggests that theophylline may help restore the sense of smell in some people. ^{1 2 3 4 5}

Is theophylline safe for human use?

Theophylline has been used in various treatments and is generally safe, but it can cause side effects like stomach issues, heart problems, and nervous system effects in some people. The risk of side effects is higher with larger doses, but smoking seems to reduce these risks. ^{1 2 4 6 7}

How is the drug CYR-064 (Theophylline) unique in treating loss of smell?

CYR-064 (Theophylline) is unique because it is a phosphodiesterase inhibitor that can improve smell function by increasing levels of certain molecules (cAMP and cGMP) in nasal mucus, which are often low in people with smell loss. Unlike other treatments, it can be administered both orally and intranasally, offering flexibility in treatment options. ^{1 2 3 4 8}

What is the purpose of this trial?

This trial is testing a new treatment called CYR-064 to see if it is safe and works well. About 150 people will take part in the study. The trial will last several months, including initial checks, treatment, and follow-up periods.

Research Team

Mas Takashima, MD

Principal Investigator

The Methodist Hospital Research Institute

Eligibility Criteria

This trial is for men and women aged 18-65 who've lost their sense of smell but don't have any nasal blockages or diseases causing it. They must be able to take the study drug themselves and follow the trial's procedures.

Inclusion Criteria

Endoscopy of the nasal cavity reveals no structural or pathologic issues that would impede delivery of study drug to olfactory receptors, as concluded by the Investigator.

I can take the study drug as directed and follow the study's schedule.

You have had a CT scan of your nose within the past two years with no identifiable structural or pathologic issue that would prevent study drug from reaching olfactory receptors.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive either CYR-064 or placebo nasal solution twice a day for 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Treatment Details

Interventions

• CYR-064

Trial Overview The trial tests CYR-064 against a placebo to see if it's safe and works for people with reduced sense of smell. Participants are randomly chosen to receive either CYR-064 or a fake drug, without knowing which one they get.

Participant Groups

Group I: CYR-064 dose 2 Experimental Treatment 1 Intervention

Treatment with nasal solution of CYR-064 twice a day for 24 weeks. CYR-064 will be self-administered by patients.

Group II: CYR-064 dose 1 Active Control 1 Intervention

Treatment with nasal solution of CYR-064 twice a day for 24 weeks. CYR-064 will be self-administered by patients.

Group III: Placebo Placebo Group 1 Intervention

Treatment with Placebo nasal solution for 24 weeks. CYR-064 will be self-administered by patients.

Who Is Running the Clinical Trial?

Cyrano Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

150+

Findings from Research

In a study of 312 patients with hyposmia, oral treatment with theophylline improved smell function in over 50% of participants, indicating its potential efficacy as a treatment for smell disorders.

Responders to theophylline treatment had higher levels of nasal mucus cAMP and cGMP compared to nonresponders, suggesting that these biomarkers may help predict which patients are more likely to benefit from theophylline therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative resistance to oral theophylline treatment in patients with hyposmia manifested by decreased secretion of nasal mucus cyclic nucleotides. Henkin, RI., Velicu, I., Schmidt, L.[2018]

In a study of 312 patients with smell loss (hyposmia), theophylline treatment led to significant improvements in smell function, with 50.3% of patients reporting subjective improvement and 21.7% achieving normal smell function.

Higher doses of theophylline (600-800 mg) were more effective than lower doses, and improvements in smell function persisted as long as treatment was maintained, with follow-up periods ranging from 6 to 72 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label controlled trial of theophylline for treatment of patients with hyposmia. Henkin, RI., Velicu, I., Schmidt, L.[2013]

In a study involving 22 adults with post-viral olfactory dysfunction, intranasal theophylline saline irrigation was found to be safe, with no adverse events reported and undetectable serum theophylline levels in most patients.

While slightly more patients in the theophylline group reported improved smell compared to placebo, the differences were not clinically meaningful, indicating that larger trials or dose adjustments may be necessary to achieve significant treatment effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Smell Changes and Efficacy of Nasal Theophylline (SCENT) irrigation: A randomized controlled trial for treatment of post-viral olfactory dysfunction. Lee, JJ., Peterson, AM., Kallogjeri, D., et al.[2023]

Theophylline, an oral medication used to treat hyposmia, was found in nasal mucus after administration, indicating it can effectively reach the nasal area where it may help correct smell loss.

In a study involving 23 hyposmic patients, the levels of theophylline in nasal mucus were found to be 74% of those in serum and 111% compared to saliva, suggesting that nasal mucus can be a reliable, noninvasive way to monitor theophylline levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative monitoring of oral theophylline treatment in blood serum, saliva, and nasal mucus. Henkin, RI.[2013]

In a pilot study involving 10 patients with hyposmia and hypogeusia, intranasal theophylline methylpropyl paraben was found to be more effective than oral theophylline in improving taste and smell acuity, with 8 out of 10 patients showing improvement after just 4 weeks of treatment.

Intranasal theophylline treatment was also associated with no adverse effects and resulted in a greater increase in body weight compared to oral administration, suggesting it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal theophylline treatment of hyposmia and hypogeusia: a pilot study. Henkin, RI., Schultz, M., Minnick-Poppe, L.[2012]

In a study of 2,766 medical inpatients, 10.8% experienced adverse reactions to theophylline, with gastrointestinal issues being the most common (7.8%).

Higher doses of theophylline were linked to more adverse effects, while current cigarette smoking appeared to reduce the frequency of these reactions, particularly in younger patients with normal kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical toxocity of theophylline in relation to cigarette smoking. A report from the Boston Collaborative Drug Surveillance Program. Pfeifer, HJ., Greenblatt, DJ.[2019]

In a randomized crossover study involving 12 elderly patients with chronic airflow obstruction, Uniphyl tablets (a once-daily theophylline preparation) significantly improved peak expiratory flow rates compared to Theo-Dur tablets and placebo, indicating better efficacy in managing airflow obstruction.

Despite observing cardiac ectopy in most patients, there was no significant increase in ectopic activity during the theophylline treatments compared to placebo, suggesting that Uniphyl tablets may be safe for use in this population without exacerbating cardiac issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of once-daily Uniphyl tablets compared with twice-daily Theo-Dur tablets in elderly patients with chronic airflow obstruction. Rivington, RN., Calcutt, L., Hodder, RV., et al.[2019]

Theophylline, an unspecific phosphodiesterase inhibitor, appears to be taken up by the olfactory epithelium in mice and may interact with olfactory signal transduction, as indicated by changes in electro-olfactogram (EOG) responses.

Administration of theophylline led to a significant decrease in EOG amplitudes during olfactory stimulation, suggesting it may negatively impact olfactory sensitivity rather than enhance it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Theophylline induces changes in the electro-olfactogram of the mouse. Gudziol, V., Pietsch, J., Witt, M., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Relative resistance to oral theophylline treatment in patients with hyposmia manifested by decreased secretion of nasal mucus cyclic nucleotides. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

An open-label controlled trial of theophylline for treatment of patients with hyposmia. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Smell Changes and Efficacy of Nasal Theophylline (SCENT) irrigation: A randomized controlled trial for treatment of post-viral olfactory dysfunction. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Comparative monitoring of oral theophylline treatment in blood serum, saliva, and nasal mucus. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Intranasal theophylline treatment of hyposmia and hypogeusia: a pilot study. [2012]

6. United States pubmed.ncbi.nlm.nih.gov

Clinical toxocity of theophylline in relation to cigarette smoking. A report from the Boston Collaborative Drug Surveillance Program. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of once-daily Uniphyl tablets compared with twice-daily Theo-Dur tablets in elderly patients with chronic airflow obstruction. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Theophylline induces changes in the electro-olfactogram of the mouse. [2021]