The primary objective of this study is to demonstrate the superiority of etripamil NS over placebo in reducing ventricular rate in patients with AF.
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 demonstrate the superiority of
etripamil NS over placebo in reducing ventricular rate in patients with AF.
Secondary outcome
The secondary objective is to evaluate the safety and efficacy of etripamil NS
in patients with AF.
Background summary
Etripamil an L-type calcium channel antagonist and short-acting verapamil
analog, is currently being developed for the treatment of paroxysmal
supraventricular tachycardia (PSVT), and other arrhythmias.
Atrial fibrillation (AF) is the most common sustained arrhythmia in humans,
with an irregular and often rapid heart rate that increases the risk of stroke
and heart failure. For most patients, current treatment for AF consists of
anti-coagulant therapy, either warfarin or novel oral anti-coagulants to reduce
the risk of blood clot embolization and stroke; those who cannot take these
stronger blood thinners may be prescribed aspirin, but aspirin has only been
shown to be somewhat efficacious in a very small and specific population. With
regard to the abnormal heart rate that occurs during AF, there are two
strategies. One strategy focuses on controlling the heart rate during AF to
reduce or eliminate symptoms, while the other takes aim at terminating AF and
maintaining sinus rhythm. The major unmet needs are for more efficacious and
safer rhythm-control drugs as well as rate-control drugs with a faster onset of
action to bring down the heart rate. Based on data from both the Phase 1 and
Phase 2 studies, etripamil has demonstrated its ability to prolong conduction
through the AV node, which is key to reducing the ventricular rate during AF.
This makes etripamil an excellent candidate for use in controlling the
ventricular rate in a subset of patients with AF.
Study objective
The primary objective of this study is to demonstrate the superiority of
etripamil NS over placebo in reducing ventricular rate in patients with AF.
Study design
This is a multi-center, randomized, double-blind, placebo-controlled study to
evaluate the effects of etripamil NS in patients with AF. This study includes
screening procedures, treatment procedures, and a follow-up period. Patients
will be randomized in a double-blind fashion to yield at least 50 evaluable
patients in 2 groups of at least 25 patients each (Efficacy Population). Each
patient will receive a single dose of Placebo or 70 mg etripamil intranasally.
Patients will be contacted for follow-up the next day and 7 days after dosing.
Total duration of participation is 1 week.
Intervention
1 Group of patients will receive a single dose of intranasal admnistration of
etripamil 70 mg, while the other group will receive placebo.
Study burden and risks
The primary benefit of this study is that etripamil nasal spray may provide
rapid symptom relief to patients with atrial fibrillation by decreasing the
ventricular response rate.
The potential risks of study participation include those associated with
exposure to etripamil and the risks of medical evaluation. AEs associated with
etripamil include nasal irritation, nasal discomfort, and throat irritation.
Potential adverse events which have been rare or not observed in
studies to date include other cardiac arrhythmias, or AEs associated with drops
in blood pressure (dizziness, headache).
1111 Dr. Frederik-Philips Blvd., Suite 420
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Listed location countries
Age
Inclusion criteria
1. Aged 18 years and over
2. Has provided written informed consent
3. Patients with episodes of paroxysmal, persistent or permanent AF, presenting
with AF and a ventricular rate >=110 bpm, measured over 1 minute on an ECG
4. Patients should receive appropriate antithrombotic therapy as per Canadian
Cardiovascular Society (CCS) guidelines.
a. Etripamil (a calcium channel blocker) is intended for acute rate control
only. If rhythm control is desired (outside of the present protocol),
anticoagulation as per CCS guidelines may start after the administration of
study drug.
Exclusion criteria
1. Has evidence of atrial flutter (ECG) at presentation
2. Has a history of stroke, transient ischemic attack, or peripheral embolism
within the last 3
months
3. Has received by IV route any of the following within one hour before study
drug
administration: flecainide, procainamide, digoxin, beta-blocker, or calcium
chanel blocker
4. Has signs and symptoms of severe congestive heart failure at presentation
(e.g. tachypnea,
oxygen desaturation <90% unless due to known pulmonary disease, pulmonary
rales, sign
of peripheral hypoperfusion)
5. Hemodynamic instability, with systolic blood pressure <90 mmHg or diastolic
blood
pressure <60 mmHg
6. Known uncorrected severe aortic or mitral stenosis
7. Hypertrophic cardiomyopathy with outflow tract obstruction
8. Has a history of second- or third-degree atrioventricular block
9.Regular rhythm suggesting a complete AV block
10. Has a history or evidence of torsades de pointes, sick sinus syndrome, or
Brugada syndrome
11. Evidence of Acute Coronary Syndrome within the last 12 months except if
patient was
successfully revascularized
12. Positive pregnancy test result at screening, and females of childbearing
potential who do
not agree to use adequate method of contraception for the duration of the
study
13. Has evidence of any clinically significant acute or chronic condition of
the nasal cavity
(e.g., rhinitis or deviated septum) which could interfere with administration
of the study
drug in either or both nasal cavities
14. Has a history of sensitivity to verapamil
15. Has previously participated in a clinical study for etripamil
16. Has a history of sensitivity to any components of the investigational
product.
17. Signs of alcohol or drugs intoxication at the time of presentation which,
in the opinion of
the Investigator, would impact the validity of study results;
18. Is currently participating in another drug or device study, or has received
an investigational
drug or device within 30 days of Screening
19. Has evidence of clinically significant cardiovascular, endocrine,
gastrointestinal,
hematologic, hepatic, immunologic, neurologic, oncologic, pulmonary,
psychiatric, or
renal disease or any other condition which, in the opinion of the Investigator,
would
jeopardize the safety of the patient or impact the validity of study results.
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 | EUCTR2022-001854-49-NL |
| ClinicalTrials.gov | NCT04467905 |
| CCMO | NL82019.056.22 |