Primary:1. The primary objective is to evaluate the safety of self-administered etripamil nasal spray (NS) outside of the clinical settingSecondary Objectives:1. To evaluate the efficacy of self-administered etripamil NS outside of the clinical…
ID
Source
Brief title
Condition
- Cardiac arrhythmias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of this study is to evaluate the safety of
selfadministered etripamil NS. Efficacy variables will be collected as
secondary or exploratory analyses.
Safety variables will include clinical adverse events (AEs), vital signs, and
arrhythmias and conduction disorders detected on surface ECG or CMS
recordings.
Secondary outcome
The secondary efficacy endpoints will include:
• Frequency of additional medical intervention to treat PSVT, as measured by
emergency department (ED) visits, hospital admissions,
and concomitant medication use.
• Improvement in patient quality of life, as measured by the BIPQ, CAQ, SF-36
questionnaire and other surveys.
• Patient satisfaction with treatment, as measured by the Treatment
Satisfaction Questionnaire for Medication (TSQM-9) and other
questions.
• Termination of PSVT episodes.
The exploratory endpoints will include:
• Frequency of PSVT episodes, and use of etripamil NS for those episodes, as
captured by the PRO.
• Characteristics of patient PSVT episodes, as measured by the data collected
by the CMS.
Background summary
Etripamil, an L-type calcium channel antagonist and short-acting verapamil
analog, is being developed by Milestone Pharmaceuticals Inc. (hereinafter
Milestone) for the treatment of paroxysmal supraventricular tachycardia (PSVT),
used in reference to both the disorder and its associated tachyarrhythmia. A
relatively common disorder, PSVT is characterized by episodes of
tachyarrhythmia typically with a heart rate (HR) over 100 bpm and a QRS
duration of <120 msec. Etripamil is directed towards the 2 most common subtypes
of PSVT, atrioventricular (AV) nodal reentrant tachycardia (AVNRT) and AV
reentrant tachycardia (AVRT), together accounting for approximately 90% of PSVT
cases. In both conditions, a pharmaceutical agent capable of transiently
prolonging AV conduction time can result in arrhythmia termination and
restoration of normal sinus rhythm (SR). Historically, intravenous (IV)
verapamil has been used as an effective agent for treatment of acute episodes
of PSVT. However, it has been replaced in recent years by IV adenosine, which
is equally effective in terminating acute episodes of PSVT. Adenosine has the
advantage of having a very short half-life, as it is rapidly metabolized during
the time required to terminate an episode of PSVT. However, the short half-life
of adenosine renders it ineffective when given via routes of administration
other than IV. As both of these medications require the establishment of IV
access, they are not appropriate for a patient self-administration paradigm in
an outpatient setting.
Study objective
Primary:
1. The primary objective is to evaluate the safety of self-administered
etripamil nasal spray (NS) outside of the clinical setting
Secondary Objectives:
1. To evaluate the efficacy of self-administered etripamil NS outside of the
clinical setting, and
2. To evaluate the impact of etripamil NS on PSVT disease burden, and
3. To evaluate the safety and efficacy of etripamil NS when used for multiple
PSVT episodes
Study design
NODE-303 is a multi-center, open label study all patients will be provided with
an ambulatory Cardiac Monitoring System (CMS) to help document PSVT episodes.
The CMS will be self-applied by the patient, when PSVT symptoms begin. Patients
will self-administer etripamil NS if vagal maneuver is ineffective. After an
episode of PSVT where drug is administered, the patient will return to the
investigative site for a study visit and will be given the option to continue
in NODE-303 and manage subsequent episodes of PSVT with etripamil NS up to 4
treatments with etripamil NS.
Intervention
when PSVT symptoms begin. Patients will self-administer etripamil NS if vagal
maneuver is ineffective.
Study burden and risks
the burden and risk of the study mainly consist out of extra time spend in
comparision to standard treatment (going to the study site and completing
surveys) and side effects.
possible side effects of etripamil NS:
• Nasal congestion (stuffy nose)
• Nasal discomfort
• Eyes watering
• Rhinorrhea (runny nose)
• Sore throat
• Cough
• Sneezing
• Bleeding from the nose
• Decrease in heart rate and/or a drop in blood pressure (hypotension), with
symptoms that include dizziness and fainting. In severe cases, low blood
pressure can be life-threatening.
• A condition called heart block, where a naturally occurring electrical signal
that controls the heartbeat is partially or completely blocked from reaching
the heart*s ventricles (the 2 large chambers in the heart that collect and
distribute blood from the heart to the rest of the body). In severe cases,
heart block can be life-threatening.
Patients have the benefit of the possibility to self administer the study drug
to stop a PSVT episode and do not need to go to a hospital directly when having
a PSVT episode.
Dr. Frederik-Philips Boulevard, Suite 420 1111
Montreal, Quebec CA H4M 2X6
CA
Dr. Frederik-Philips Boulevard, Suite 420 1111
Montreal, Quebec CA H4M 2X6
CA
Listed location countries
Age
Inclusion criteria
1) Has been diagnosed with PSVT by a medical professional and reports having at
least one previous episode of PSVT. For clarity, PSVT refers to episodic SVT
that includes the AV node as a critical part of reentrant circuit.
2) Is of at least 18 years of age
3) Signed NODE-303 written informed consent
4) Women of child-bearing potential must be willing to use at least 1 form of
contraception during the trial, and must be willing to discontinue from the
study should they become or plan to become pregnant
5) Willing and able to comply with study procedures
Exclusion criteria
1) Patients with only a history of atrial arrhythmia that does not involve the
atrioventricular (AV) node as part of the tachycardia circuit (e.g., atrial
fibrillation, atrial flutter, intra-atrial tachycardia) are not eligible.
Patients with a history of these tachycardias who are also diagnosed with PSVT
are eligible.
2) History of allergic reaction to verapamil
3) Current therapy with digoxin, or any Class I or III antiarrhythmic drug.
Patients may be eligible if these drugs are stopped at least five half-lives
before the administration of etripamil NS. The only exception is amiodarone
which must be stopped 30 days before enrollment.
4) History of ventricular pre-excitation, e.g., delta waves,
Wolff-Parkinson-White syndrome.
5) History of a second- or third-degree AV block
6) Symptoms of congestive heart failure New York Heart Association Class II to
IV
7) Significant physical or psychiatric condition including alcoholism or drug
abuse, which, in the opinion of the Investigator, could jeopardize the safety
of the patient, or impede the patient*s capacity to follow the study procedures
8) History of syncope due to an arrhythmic etiology at any time, or history in
last 5 years of unexplained syncope
9) Is pregnant or breastfeeding
10) Previously enrolled in a clinical trial for etripamil and received study
drug
11) History of ACS or stroke within 6 months of screening
12) Evidence of renal dysfunction as determined by an estimated glomerular
filtration rate assessed at the Screening Visit as follows:
a) < 60mL/min/1.73m2 for patients < 60 years of age
b) < 40mL/min/1.73m2 for patients >=60 and < 70 years of age
c) < 35mL/min/1.73m2 for patients >=70 years of age
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-001857-13-NL |
| ClinicalTrials.gov | NCT04072835 |
| CCMO | NL71299.100.19 |