Etripamil Nasal Spray for Rapid Heartbeat

Recruiting at9 trial locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Milestone Pharmaceuticals Inc.

Must not be taking: Beta blockers, Calcium blockers

Disqualifiers: Atrial arrhythmia, Long QT, others

No Placebo Group

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

NODE-202 is a Phase 2, multicenter, multinational, single dose, open-label, 2-part, sequential design study in pediatric patients with an established diagnosis of paroxysmal supraventricular tachycardia (PSVT) presenting with a symptomatic episode of PSVT. In Part 1, at least 30 patients aged 12 to \<18 years will be enrolled and treated with etripamil nasal spray (NS). Efficacy, safety, tolerability and PK (for at least 12 patients) will be assessed after administration of 70 mg etripamil NS (Part 1A). At least 18 subsequent patients will be enrolled and treated with the etripamil NS with the dose determined by the Pharmacokinetic (PK) analysis and will undergo efficacy and safety/tolerability assessments (Part 1B). In Part 2, at least 30 patients aged 6 to \<12 years will be enrolled and treated with etripamil NS at a dose selected based on appropriate body size-based modeling, as well as efficacy, safety/tolerability, and PK data collected in Part 1. Efficacy, safety, tolerability and PK (for at least 12 patients) will be assessed after administration of etripamil NS (Part 2A). At least 18 subsequent patients will be enrolled and treated with the etripamil NS with the dose determined by the PK analysis and will undergo efficacy and safety/tolerability assessments (Part 2B). The study will include the following visits: A Screening Visit, A Treatment Visit, , and A Follow-Up/End of Study Visit.

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.

How is Etripamil Nasal Spray different from other drugs for rapid heartbeat?

Etripamil Nasal Spray is unique because it is administered through the nose, allowing for rapid absorption and quick action, which is beneficial for treating rapid heartbeat. This nasal route avoids the first-pass metabolism that occurs with oral medications, potentially leading to higher bioavailability and faster relief. ^{1 2 3 4 5}

Research Team

David Bharucha, MD

Principal Investigator

Milestone Pharmaceuticals

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Etripamil NS (Calcium Channel Blocker)

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.

Participant Groups

Group I: Etripamil NS 70mg Experimental Treatment 1 Intervention

Patients will be administered by study site personnel

Who Is Running the Clinical Trial?

Milestone Pharmaceuticals Inc.

Lead Sponsor

Trials

11

Recruited

4,500+

Findings from Research

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]

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]

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]

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]

References

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

Onset of action of aqueous beclomethasone dipropionate nasal spray in seasonal allergic rhinitis. [2019]

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

Long-term efficacy and safety of once-daily treatment with beclomethasone dipropionate nasal aerosol. [2016]

3. United States 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. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioavailability of metoclopramide nasal spray versus metoclopramide intravenous in healthy volunteers and cancer patients. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Metoclopramide nasal spray in vitro evaluation and in vivo pharmacokinetic studies in dogs. [2018]