Taplucainium for Chronic Cough

(ASPIRE Trial)

Recruiting at 88 trial locations

Overseen By Nocion Clinical Trials

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Nocion Therapeutics

Must not be taking: Opiates, Opioids

Disqualifiers: Pulmonary disease, Smoking, Malignancy, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a phase 2b, randomized, double-blind, placebo-controlled study investigating the efficacy, safety, and tolerability of Taplucainium Inhalation Powder (NOC-110) once daily in adults with refractory or unexplained chronic cough.

Do I need to stop taking my current medications to join the trial?

Yes, you need to stop taking medications and treatments that can impact cough during the study.

What data supports the idea that the drug Taplucainium for Chronic Cough is an effective treatment?

The available research does not provide specific data on Taplucainium for Chronic Cough. Instead, it discusses other treatments like tiotropium and lidocaine for cough-related conditions. Tiotropium is shown to help with cough in asthma and COPD by reducing mucus and relaxing airways. Lidocaine is effective in suppressing severe coughs in conditions like asthma and COPD. However, there is no direct evidence in the provided information about Taplucainium's effectiveness for chronic cough. ^{1 2 3 4 5}

What safety data exists for Taplucainium (NOC-110, NTX-1175) for chronic cough?

The provided research does not contain any safety data for Taplucainium (NOC-110, NTX-1175) for chronic cough. The studies focus on non-vitamin K antagonist oral anticoagulants (NOACs) for atrial fibrillation and do not mention Taplucainium or its related names. ^{6 7 8 9 10}

Is the drug Taplucainium a promising treatment for chronic cough?

The provided research articles do not contain any information about Taplucainium or its effectiveness for treating chronic cough. Therefore, we cannot determine if it is a promising treatment based on the given data. ^{11 12 13 14 15}

Research Team

Bernard L Silverman, MD

Principal Investigator

Chief Medical Officer Nocion Therapeutics, Inc.

Eligibility Criteria

This trial is for adults who've had a chronic cough that hasn't improved or doesn't have an explanation, lasting at least 12 months. Participants must be able to consent and follow contraceptive guidelines if they can have children.

Inclusion Criteria

I can understand and agree to the study's procedures and risks.

I agree to follow the study's birth control requirements.

I have had a chronic cough for over a year that hasn't improved.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily inhalation of NOC-110 or placebo for chronic cough

13 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• NOC-110 (Other)

Trial Overview The study tests NOC-110 (Taplucainium Inhalation Powder) against a placebo to see if it's effective, safe, and tolerable for treating long-lasting coughs. It's randomized and double-blind, meaning neither the researchers nor participants know who gets the real treatment.

Participant Groups

Group I: NOC-110 6mg Experimental Treatment 1 Intervention

NOC-110 (taplucainium) administered by daily dry powder inhalation. NOC-110 contains a dry powder lactose blend containing drug substance taplucainium administered using an available inhaler.

Group II: NOC-110 3mg Experimental Treatment 1 Intervention

NOC-110 (taplucainium) administered by daily dry powder inhalation. NOC-110 contains a dry powder lactose blend containing drug substance taplucainium administered using an available inhaler.

Group III: NOC-110 1mg Experimental Treatment 1 Intervention

NOC-110 (taplucainium) administered by daily dry powder inhalation. NOC-110 contains a dry powder lactose blend containing drug substance taplucainium administered using an available inhaler.

Group IV: Placebo Placebo Group 1 Intervention

The matching placebo contains inhalation grade lactose blended with arginine. The blend is taste masked to the active drug product to minimize unblinding due to taste differences. The matching placebo will be administered via the same inhaler.

Who Is Running the Clinical Trial?

Nocion Therapeutics

Lead Sponsor

Trials

2

Recruited

350+

Iqvia Pty Ltd

Industry Sponsor

Trials

120

Recruited

177,000+

Ari Bousbib

Iqvia Pty Ltd

Chief Executive Officer since 2016

MBA from Columbia University, Master of Science in Mathematics and Mechanical Engineering from Ecole Superieure des Travaux Publics, Paris

Jeffrey Spaeder

Iqvia Pty Ltd

Chief Medical Officer

MD

Findings from Research

Tiotropium effectively blocks cough reflexes in guinea pigs by inhibiting TRPV1-mediated sensory nerve activity, which is a novel mechanism beyond its known anticholinergic effects.

The study suggests that the clinical benefits of tiotropium in managing symptoms of chronic obstructive pulmonary disease and asthma may be partly due to its ability to directly modulate airway sensory nerves, as demonstrated through various experimental techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiotropium modulates transient receptor potential V1 (TRPV1) in airway sensory nerves: A beneficial off-target effect? Birrell, MA., Bonvini, SJ., Dubuis, E., et al.[2022]

This network meta-analysis of 24 studies involving 21,311 COPD patients found that newer long-acting muscarinic antagonists (LAMAs) like aclidinium, glycopyrronium, and umeclidinium showed comparable efficacy to tiotropium, the established standard treatment, in improving lung function as measured by trough FEV1.

All LAMAs demonstrated significant improvements in respiratory symptoms and reduced rescue medication use compared to placebo, suggesting they are effective options for managing COPD, with the choice of treatment depending on individual patient and physician preferences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of long-acting muscarinic antagonist monotherapies in COPD: a systematic review and network meta-analysis. Ismaila, AS., Huisman, EL., Punekar, YS., et al.[2022]

In a study involving 8 female patients with idiopathic interstitial pneumonia, aerosolized carcainium chloride (VRP700) significantly reduced cough frequency and improved quality of life compared to a placebo, with results showing a high level of statistical significance (P < 0.001).

The treatment was well-tolerated, with no reported adverse events or changes in safety parameters, suggesting that VRP700 is a safe option for managing cough in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitussive effect of carcainium chloride in patients with chronic cough and idiopathic interstitial pneumonias: A pilot study. Lavorini, F., Spina, D., Walker, MJ., et al.[2018]

Nebulized lidocaine was found to be very effective in suppressing intractable cough in patients with conditions like asthma, reactive airways disease, and COPD, providing relief that can improve daily activities and sleep.

This study suggests that nebulized lidocaine can serve as a temporary solution while waiting for more definitive treatments to take effect, indicating its potential utility in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lidocaine inhalation for cough suppression. Udezue, E.[2013]

In a randomized trial involving 58 patients with asthma and chronic cough unresponsive to standard treatments, tiotropium significantly improved cough severity and quality of life compared to theophylline, with both treatments showing benefits.

Tiotropium increased capsaicin cough reflex sensitivity (C-CRS), suggesting it alleviates cough by modulating this reflex, and heightened C-CRS before treatment was identified as a predictor for better response to tiotropium.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiotropium for refractory cough in asthma via cough reflex sensitivity: A randomized, parallel, open-label trial. Fukumitsu, K., Kanemitsu, Y., Kurokawa, R., et al.[2023]

In a study of 6,392 patients with atrial fibrillation, off-label use of non-vitamin K antagonist anticoagulants (NOACs) at reduced doses significantly increased the risk of thromboembolism by 2.5 times compared to warfarin.

However, using NOACs at standard doses showed similar safety and effectiveness to well-controlled warfarin, indicating that proper dosing is crucial for optimal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Off-label Dosing of Non-vitamin K Antagonist Anticoagulant for Atrial Fibrillation in Asian Patients. Lee, KN., Choi, JI., Boo, KY., et al.[2022]

In a study of 20,967 diabetic patients with atrial fibrillation, those taking non-vitamin K antagonist oral anticoagulants (NOACs) experienced significantly lower risks of major adverse cardiovascular events, major adverse limb events, and major bleeding compared to those on warfarin.

The benefits of NOACs were particularly pronounced in older patients (≥75 years) and those with additional risk factors like ischemic heart disease, suggesting that NOACs may be a safer and more effective option for high-risk diabetic AF patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness, safety, and major adverse limb events in atrial fibrillation patients with concomitant diabetes mellitus treated with non-vitamin K antagonist oral anticoagulants. Chan, YH., Lee, HF., Li, PR., et al.[2022]

NOC/c drugs, which are approved with limited safety and efficacy data, are more likely to receive serious safety warnings compared to drugs with a standard review, indicating potential safety concerns post-approval.

Despite not being more likely to receive warnings than priority-reviewed drugs, NOC/c drugs spend less time in the review process, suggesting that Health Canada may need to extend review times and enhance post-market safety monitoring for these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-market safety warnings for drugs approved in Canada under the Notice of Compliance with conditions policy. Lexchin, J.[2018]

Patients with atrial fibrillation who are eligible for reduced-dose non-vitamin K antagonist oral anticoagulants (NOACs) have higher annualized rates of stroke and major bleeding compared to those eligible for full-dose NOACs, indicating a need for careful monitoring and dose adjustment.

When appropriately dose-adjusted, reduced-dose NOACs show a favorable benefit-harm profile compared to warfarin, suggesting that they can effectively reduce the risks of thromboembolic and hemorrhagic complications in indicated patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of reduced-dose non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: a meta-analysis of randomized controlled trials. Wang, KL., Lopes, RD., Patel, MR., et al.[2020]

In a meta-analysis of nine studies involving 144,797 patients with atrial fibrillation, off-label underdosing of rivaroxaban was linked to a 31% increased risk of stroke or systemic embolism.

Off-label underdosing of apixaban was associated with a 21% higher risk of all-cause death, while no significant differences were found for dabigatran or edoxaban when comparing off-label to on-label dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-label underdosing of four individual NOACs in patients with nonvalvular atrial fibrillation: A systematic review and meta-analysis of observational studies. Sang, C., Chen, J., Sun, J., et al.[2022]

In a study of 12 stable cystic fibrosis lung transplant recipients, switching from tacrolimus (TAC) twice daily to once daily required a dose adjustment for 82% of patients to maintain therapeutic levels.

The mean dose increase after conversion was 28%, indicating that while the switch to once daily dosing is feasible, careful monitoring and adjustment are necessary to ensure effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose increase needed in most cystic fibrosis lung transplantation patients when changing from twice- to once-daily tacrolimus oral administration. Soto, GAC., Ruiz-Antorán, B., Laporta, R., et al.[2022]

Inhaled formulations of tacrolimus (TAC) combined with lactose were found to be safe and well-tolerated in healthy subjects, with only mild side effects like cough and throat irritation reported.

The study demonstrated that both colloidal dispersions and dry powder forms of TAC-LAC had low systemic absorption, suggesting that this method of delivery could effectively target the lungs while minimizing side effects, making it a promising therapy for lung transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Safety and Tolerability Study of Thin Film Freeze-Dried Tacrolimus for Local Pulmonary Drug Delivery in Human Subjects. Sahakijpijarn, S., Beg, M., Levine, SM., et al.[2021]

Prolonged-release tacrolimus, taken once daily, offers a slower release and lower peak concentration compared to the immediate-release version, which is taken twice daily, potentially improving patient adherence.

Both formulations show a strong correlation between trough concentration and overall drug exposure, meaning that monitoring trough levels can effectively guide dosing for patients on prolonged-release tacrolimus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of prolonged-release tacrolimus and implications for use in solid organ transplant recipients. Tanzi, MG., Undre, N., Keirns, J., et al.[2018]

Older adult kidney transplant recipients (aged ≥ 65 years) required significantly lower doses of extended-release tacrolimus (LCP-Tac) compared to younger recipients and the FDA's recommended starting dose, indicating a need for dose adjustments in this population.

There were no significant differences in graft outcomes or adverse effects between older adults receiving LCP-Tac and those receiving immediate-release tacrolimus (IR-Tac), suggesting that LCP-Tac is a safe and effective option for this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Experience with Extended-Release Tacrolimus in Older Adult Kidney Transplant Recipients: A Retrospective Cohort Study. January, SE., Hagopian, JC., Nesselhauf, NM., et al.[2021]

Converting stable kidney transplant recipients from the twice-daily tacrolimus formulation (Prograf) to the once-daily formulation (Advagraf) resulted in significant reductions in glycemia and triglyceride levels, which may improve long-term graft and patient survival.

The study involved 40 patients (20 in each group) who had been on Prograf for over 6 months, and the conversion did not negatively impact graft function, as blood pressure and kidney function remained stable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once daily tacrolimus formulation: monitoring of plasma levels, graft function, and cardiovascular risk factors. Meçule, A., Poli, L., Nofroni, I., et al.[2022]

References

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

Tiotropium modulates transient receptor potential V1 (TRPV1) in airway sensory nerves: A beneficial off-target effect? [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Comparative efficacy of long-acting muscarinic antagonist monotherapies in COPD: a systematic review and network meta-analysis. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Antitussive effect of carcainium chloride in patients with chronic cough and idiopathic interstitial pneumonias: A pilot study. [2018]

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

Lidocaine inhalation for cough suppression. [2013]

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

Tiotropium for refractory cough in asthma via cough reflex sensitivity: A randomized, parallel, open-label trial. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Off-label Dosing of Non-vitamin K Antagonist Anticoagulant for Atrial Fibrillation in Asian Patients. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Effectiveness, safety, and major adverse limb events in atrial fibrillation patients with concomitant diabetes mellitus treated with non-vitamin K antagonist oral anticoagulants. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Post-market safety warnings for drugs approved in Canada under the Notice of Compliance with conditions policy. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of reduced-dose non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: a meta-analysis of randomized controlled trials. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Off-label underdosing of four individual NOACs in patients with nonvalvular atrial fibrillation: A systematic review and meta-analysis of observational studies. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Dose increase needed in most cystic fibrosis lung transplantation patients when changing from twice- to once-daily tacrolimus oral administration. [2022]

12. Switzerland pubmed.ncbi.nlm.nih.gov

A Safety and Tolerability Study of Thin Film Freeze-Dried Tacrolimus for Local Pulmonary Drug Delivery in Human Subjects. [2021]

13. Denmark pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of prolonged-release tacrolimus and implications for use in solid organ transplant recipients. [2018]

14. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical Experience with Extended-Release Tacrolimus in Older Adult Kidney Transplant Recipients: A Retrospective Cohort Study. [2021]

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

Once daily tacrolimus formulation: monitoring of plasma levels, graft function, and cardiovascular risk factors. [2022]