Etripamil Nasal Spray for Rapid Heartbeat

Recruiting at 9 trial locations

Overseen By Cameron Szakacs, PhD

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Milestone Pharmaceuticals Inc.

Must not be taking: Beta blockers, Calcium blockers

Disqualifiers: Atrial arrhythmia, Long QT, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Single dose

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a nasal spray called etripamil for treating rapid heartbeats in children diagnosed with paroxysmal supraventricular tachycardia (PSVT), a condition causing sudden and frequent episodes of fast heartbeats. Researchers aim to evaluate the spray's effectiveness and safety for children experiencing these episodes. The trial seeks children with documented PSVT episodes, regardless of past heart procedures. Participants will help determine the optimal spray dose based on their size and other factors. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as IV beta-blockers, calcium channel blockers, and amiodarone, before participating. If you are on any investigational drugs or specific antiarrhythmic agents, you may also need to discontinue them. Please discuss with the study team to understand which medications you need to stop.

Is there any evidence suggesting that etripamil nasal spray is likely to be safe for humans?

Research has shown that etripamil nasal spray is generally safe for use. One study demonstrated that the spray quickly stopped episodes of paroxysmal supraventricular tachycardia (PSVT) with a high success rate. No serious side effects led to the study's termination or resulted in death. Common side effects, such as a stuffy nose or headache, occurred in more than 10% of participants but were not severe.

Another study found that fewer people needed emergency room visits when using etripamil nasal spray, suggesting the treatment is well-tolerated. While some side effects were noted, overall safety data from multiple studies indicates that etripamil nasal spray is a promising and manageable option for treating episodes of rapid heartbeat. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike other treatments for rapid heartbeat, such as beta-blockers and calcium channel blockers that often require oral administration and can take time to work, Etripamil nasal spray offers a fast-acting alternative. This nasal spray is unique because it is designed to be administered quickly and easily, providing rapid relief by directly targeting the heart's electrical activity through a novel delivery method. Researchers are excited about Etripamil because its quick absorption through the nasal passages could make it a game-changer for patients needing immediate intervention to manage episodes of rapid heartbeat.

What evidence suggests that etripamil nasal spray could be an effective treatment for rapid heartbeat?

Research has shown that etripamil nasal spray, which participants in this trial will receive, can help manage paroxysmal supraventricular tachycardia (PSVT), a condition characterized by a very fast heart rate. In earlier studies, patients using etripamil experienced better symptom relief and a slower heart rate during PSVT episodes compared to those using a placebo. Over 1,000 episodes treated with etripamil mostly resulted in mild side effects, indicating the treatment is both effective and safe. In everyday use, etripamil has been well-tolerated by patients, making it a promising option for those with PSVT. ^{3 6 7 8 9}

Who Is on the Research Team?

David Bharucha, MD

Principal Investigator

Milestone Pharmaceuticals

Are You a Good Fit for This Trial?

The NODE-202 study is for kids and teens with a rapid heartbeat condition called PSVT. Participants aged 12 to less than 18 can join Part 1, while those aged 6 to less than 12 can join Part 2. They should have a BMI within the normal range for their age and sex, documented history of PSVT, and if post-ablation, evidence of PSVT recurrence. A negative pregnancy test and agreement to use contraception are required.

Inclusion Criteria

You need to use birth control unless you are not having any sexual activity.

My BMI is within the healthy range for my age and sex.

I have a history of rapid heartbeats confirmed by a heart monitor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive etripamil nasal spray during a symptomatic episode of PSVT, with efficacy, safety, tolerability, and PK assessments

Single dose

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including recording of adverse events and ECG

1 to 5 days

1 visit (in-person)

Open-label extension (optional)

Participants may opt into continuation of treatment long-term if deemed beneficial

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Etripamil NS

Trial Overview This trial tests Etripamil Nasal Spray (NS) in two age groups: first in older children (Part 1), then younger ones (Part 2). It's an open-label study where everyone gets the drug. The dose is based on body size and previous results from older participants. Researchers will check how well it works, its safety, tolerability, and how the body processes it.

How Is the Trial Designed?

Group I: Etripamil NS 70mg Experimental Treatment 1 Intervention

Patients will be administered by study site personnel

Etripamil NS is already approved in United States for the following indications:

Approved in United States as CARDAMYST for:

• Paroxysmal supraventricular tachycardia (PSVT)

Who Is Running the Clinical Trial?

Milestone Pharmaceuticals Inc.

Lead Sponsor

Trials

11

Recruited

4,500+

Published Research Related to This Trial

In a study involving 529 patients aged 12 and older, long-term treatment with beclomethasone dipropionate (BDP) nasal aerosol significantly improved nasal symptoms in patients with perennial allergic rhinitis (PAR) over 30 and 52 weeks compared to placebo.

BDP nasal aerosol was well tolerated, with a safety profile similar to placebo, although there was a higher incidence of nosebleeds (epistaxis) in the treatment group; overall, there were no clinically significant systemic safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of once-daily treatment with beclomethasone dipropionate nasal aerosol. Weinstein, SF., Andrews, CP., Shah, SR., et al.[2016]

The study developed a metoclopramide (MCP) nasal spray that demonstrated high bioavailability (62.3%) and rapid absorption compared to oral tablets (24.9%), making it an effective option for treating motion sickness-related nausea.

The nasal spray formulation was found to be safe with minimal toxicity to nasal cilia, indicating it is suitable for self-administration and offers a quick onset of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metoclopramide nasal spray in vitro evaluation and in vivo pharmacokinetic studies in dogs. Li, Y., Fan, X., Li, W., et al.[2018]

In a study of 285 patients with diabetes and gastroparesis, metoclopramide nasal spray significantly reduced symptoms in female subjects, but not in male subjects, suggesting that sex may influence treatment efficacy.

While the nasal spray was generally well-tolerated, common side effects included dysgeusia (altered taste), headache, and fatigue, indicating a need for monitoring in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metoclopramide Nasal Spray Reduces Symptoms of Gastroparesis in Women, but not Men, With Diabetes: Results of a Phase 2B Randomized Study. Parkman, HP., Carlson, MR., Gonyer, D.[2022]

A new nasal spray formulation of metoclopramide was tested in 10 healthy subjects and 10 cancer patients, showing that it is safe with no adverse events reported in healthy subjects during the study.

The pharmacokinetics of metoclopramide nasal spray were similar to intravenous administration, although cancer patients had a slightly lower peak concentration (Cmax), indicating that while effective, the absorption may vary slightly in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioavailability of metoclopramide nasal spray versus metoclopramide intravenous in healthy volunteers and cancer patients. Scaglione, F., Scanni, A., Tomirotti, M., et al.[2013]

In a 7-day study with 161 patients suffering from seasonal allergic rhinitis, beclomethasone dipropionate nasal spray showed a significant onset of relief by 24 hours, outperforming placebo in symptom relief (P = 0.05).

Patients using beclomethasone experienced continuous improvement in their symptoms over the week, with significant efficacy in reducing symptoms compared to placebo (P < or = 0.02), and only minor adverse events were reported in both treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Onset of action of aqueous beclomethasone dipropionate nasal spray in seasonal allergic rhinitis. Selner, JC., Weber, RW., Richmond, GW., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40931676/

Results From the NODE-303 Open-Label Study Results: 1054 perceived PSVT episodes were etripamil-treated in 503 of 1116 patients enrolled. TEAEs within 24 h were mostly mild or moderate ...

2. investors.milestonepharma.com investors.milestonepharma.com/news-releases/news-release-details/milestone-pharmaceuticals-present-new-analysis-investigational

Press Releases Data show consistent efficacy, safety, and tolerability findings across multiple clinical trials that evaluated self-administered etripamil.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03464019

NCT03464019 | Efficacy and Safety of Etripamil for the ... This was a three-part, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of etripamil nasal spray (NS) ...

4. ahajournals.org ahajournals.org/doi/10.1161/CIRCEP.123.011681

Self-Administered Etripamil Nasal Spray Relieved ... Etripamil nasal spray treatment improved symptoms and reduced tachycardia rate during PSVT, compared with placebo. Improved patient-reported ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/jce.70086?af=R

Etripamil Nasal Spray for Recurrent Paroxysmal ... Conclusions. Etripamil nasal spray self-administered in a real-world setting was well tolerated, effective, and had a consistent safety profile ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02296190

Efficacy and Safety of Intranasal MSP-2017 (Etripamil) for ... The primary efficacy endpoint was the rate of successful PSVT conversion to sinus rhythm lasting at least 30 seconds within 15 minutes of study drug ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30049309/

Etripamil Nasal Spray for Rapid Conversion of ... Etripamil nasal spray rapidly terminated induced SVT with a high conversion rate. The safety and efficacy results of this study provide guidance for etripamil ...

8. jacc.org jacc.org/doi/10.1016/j.jacc.2018.04.082

Etripamil Nasal Spray for Rapid Conversion of ... There were no adverse events that led to study discontinuation or death. Adverse events that occurred with an incidence of >10% in any etripamil ...

9. academic.oup.com academic.oup.com/europace/article/doi/10.1093/europace/euaf085.671/8142041

Randomized, double-blind, placebo-controlled, efficacy and ... Etripamil nasal spray (NS) is a fast-acting, intranasally ... Safety data were favorable, and significantly fewer patients sought ED ...