Etripamil Nasal Spray for Supraventricular Tachycardia

Enrolling by invitation at 27 trial locations

Overseen By Douglas Wight, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Milestone Pharmaceuticals Inc.

Must not be taking: Digoxin, Class I/III antiarrhythmics

Disqualifiers: Allergy to verapamil, Etripamil, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 4

Duration: Ongoing

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to provide ongoing access to etripamil nasal spray, a treatment for paroxysmal supraventricular tachycardia (PSVT), a condition where the heart suddenly beats much faster than normal. The research focuses on understanding patient responses to this treatment in real-world settings after a previous trial. Participants will self-administer the nasal spray when experiencing PSVT symptoms, with the option to take a second dose if needed. This trial is suitable for those who participated in an earlier etripamil study for PSVT and did not encounter major safety issues. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of this treatment.

Will I have to stop taking my current medications?

If you are currently taking digoxin or any Class I or III antiarrhythmic drugs, you will need to stop them at least five half-lives before joining the trial. If you are taking oral amiodarone, it must be stopped 30 days before enrollment.

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 treating episodes of PSVT, a type of fast heartbeat. Most side effects occurred in the nose where the spray was applied. These side effects were usually mild or moderate and resolved on their own.

In earlier studies, patients used the spray independently and found it easy to manage without a doctor's presence. This indicates that the treatment is manageable for patients on their own.

Overall, the evidence supports that etripamil nasal spray is a safe choice for those with PSVT, with most side effects being minor and temporary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for supraventricular tachycardia, which often include oral medications like beta-blockers or calcium channel blockers, Etripamil nasal spray offers a rapid, on-the-spot solution. This treatment is unique because it's a nasal spray, allowing for quick self-administration during an episode, which could provide faster relief compared to taking pills. Researchers are excited about Etripamil because it works by directly targeting calcium channels in the heart, potentially stopping an episode in its tracks without the need for hospital visits. This innovative approach could make managing supraventricular tachycardia more convenient and effective for patients.

What evidence suggests that etripamil NS might be an effective treatment for PSVT?

Research has shown that etripamil nasal spray, used by participants in this trial, effectively treats paroxysmal supraventricular tachycardia (PSVT), a type of fast heartbeat. In studies, etripamil helped 64% of people return to a normal heart rhythm within about 17 minutes, outperforming a placebo. Another study found it increased the likelihood of returning to a normal heart rhythm at 15, 30, and 60 minutes after use. Etripamil is easy to use, as it requires no needles or surgery, and patients have tolerated it well when self-administered. Overall, it offers a promising alternative to traditional PSVT treatments. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for postmenopausal women or those who can't bear children, and men with a rapid heartbeat condition called PSVT. They must have been in a prior etripamil study without significant safety issues and agree to follow the study rules. Pregnant women, people with severe heart problems, low blood pressure after etripamil use, or certain drug therapies are excluded.

Inclusion Criteria

Women of childbearing potential who are sexually active with a male partner who is not surgically sterile must be willing to use at least 1 form of highly effective contraception from the time of signed informed consent until 7 days after the last administration of etripamil NS and must be willing to discontinue from the study should they become or plan to become pregnant

Willing and able to comply with Investigator instructions on etripamil NS use and study requirements

I am a woman not capable of becoming pregnant due to menopause or surgery.

Exclusion Criteria

I have had a serious heart rhythm problem.

Is pregnant, breastfeeding, or is planning to become pregnant during the study

I do not have any health or mental conditions that would stop me from safely following the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Self-administration of etripamil NS 70 mg for acute episodes of PSVT

Ongoing

Participants receive up to 4 pre-filled devices at a time

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue treatment with etripamil NS after previous trial participation

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Etripamil NS

Trial Overview The trial tests Etripamil Nasal Spray (70 mg) using Aptar Pharma's system on patients with Paroxysmal Supraventricular Tachycardia (PSVT). It's an open-label extension for those previously in Milestone Pharmaceuticals' trials to continue treatment.

How Is the Trial Designed?

Group I: Etripamil NS 70 mg Experimental Treatment 2 Interventions

Self- administration of a dose of 70 mg of etripamil. Patients will be provided with a maximum of 4 pre-filled devices at a time. If the symptoms of PSVT persist 10 minutes after the first dose of etripamil NS 70 mg, a second dose of etripamil NS 70 mg can be self-administered by the patient. A second dose of etripamil NS 70 mg should be taken not earlier than 10, and not later than 15 minutes after the first dose.

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

Tri-Nasal Nasal Spray, containing triamcinolone acetonide, was found to be significantly more effective than placebo in relieving nasal symptoms of allergic rhinitis, with results showing improvement as early as the second day of treatment in a study involving 377 adult patients over a 2-week period.

Both the 400 microgram dose of Tri-Nasal Nasal Spray and the active control, Nasacort, demonstrated comparable safety profiles and efficacy in treating nonocular symptoms of seasonal allergic rhinitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tri-Nasal triamcinolone acetonide nasal spray 200 and 400 micrograms qd versus placebo and Nasacort triamcinolone acetonide nasal aerosol 440 micrograms qd in patients suffering from seasonal allergic rhinitis during the grass season. Rosenthal, R., Berger, W., Bronsky, E., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37753718/

Etripamil Nasal Spray for Conversion of Repeated ... In this extension study, investigational etripamil nasal spray was well tolerated for self-treating recurrent episodes of PSVT without medical supervision.

2. ahajournals.org ahajournals.org/doi/10.1161/circ.150.suppl_1.4137870

Abstract 4137870: Nasal Etripamil Spray efficacy for Acute ... Conclusion: Nasal Etripamil is effective and safe for the treatment of acute PSVT, offering a non-invasive alternative to traditional therapies.

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. jacc.org jacc.org/doi/10.1016/j.jacc.2024.03.384

Etripamil Nasal Spray for Recurrent Paroxysmal ... RAPID showed conversion-efficacy of etripamil vs placebo (64% vs 31%; P < 0.001) with a median time-to-conversion of 17.2 min vs 53.5 min, respectively. Data ...

5. mdpi.com mdpi.com/2077-0383/14/11/3720

Efficacy and Safety of Intranasal Etripamil for Paroxysmal ... Etripamil demonstrated higher conversion rates to the sinus rhythm at 15 min (RR 1.84 [95% CI: 1.32–2.48]), 30 min (RR 1.80 [95% CI: 1.38–2.35]), and 60 min (RR ...

6. 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 ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39037331/

Preclinical Safety Evaluation of Etripamil Nasal Spray in ... The NOAEL for local toxicity was 1.9 mg/kg/dose. Collectively, these data support further study of etripamil in human trials as a potential treatment for PSVT.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04952610

Study Details | NCT04952610 | Etripamil Nasal Spray in ... The safety of self-administered etripamil Nasal Spray (NS) for treatment of episodes of PSVT outside of the clinical setting as assessed by patient-reported ...