Study to Investigate the Efficacy and Safety of Etripamil for the Termination of Spontaneous episodes of rapid heartbeat, for patients with Paroxysmal Supraventricular Tachycardia (PSVT).
- Conditions
- Treatment of Paroxysmal Supraventricular TachycardiaMedDRA version: 20.0Level: LLTClassification code 10034044Term: Paroxysmal supraventricular tachycardiaSystem Organ Class: 100000004849Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2018-000308-41-DE
- Lead Sponsor
- Milestone Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 700
Patients who meet all of the following criteria will be eligible to participate in the study:
1. Male or female patients at least 18 years of age;
2. Electrographically documented history of PSVT (e.g., ECG obtained during an episode of
PSVT, Holter monitoring, loop recorder, etc.). If patient had a prior ablation for PSVT, patient
must have documented ECG evidence of PSVT post-ablation;
3. History of sustained episodes of PSVT (i.e., typically lasting approximately 20 minutes or
longer);
4. Females of childbearing potential who are sexually active with a male partner who is not surgically sterile (i.e., vasectomy) must agree to use a highly effective form of contraception from the time of signed informed consent until 30 days after the last administration of study drug. Females of childbearing potential should have a negative serum pregnancy test result at the Screening Visit and at the Final Study Visit, a negative urine pregnancy test at the Test
Dose Randomization Visit and must use a highly effective form of contraception between the visits.
5. Male patients, except those who are surgically sterile, must use a highly effective form of contraception during the 3 days after any study drug administration; and
6. Signed written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 500
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 200
Patients who meet any of the following criteria will be excluded from participation in the study:
1. Systolic blood pressure (SBP) <90 mmHg after a 5-minute rest in sitting position at theScreening Visit or before the test dose. In patients treated with a chronic prophylactic drug for PSVT (e.g., beta-blockers, verapamil, and diltiazem), the drug may be stopped for at least the equivalent of 5 half-lives, patients may be rescreened once, and chronic use of the drug cannot be restarted after randomization;
2. History of severe symptoms of hypotension, especially syncope, during episodes of PSVT;
3. History of atrial arrhythmia that does not involve the AV node as part of the tachycardia circuit (e.g., atrial fibrillation, atrial flutter, intra-atrial tachycardia);
4. History of allergic reaction to verapamil;
5. Current therapy with digoxin or any Class I or III antiarrhythmic drug, except if these drugs are stopped at least the equivalent of 5 half-lives before the Test Dose Randomization Visit;
6. Current chronic therapy with oral amiodarone, or have taken oral amiodarone within 30 days prior to the Test Dose Randomization Visit;
7. Evidence of ventricular pre-excitation (e.g., delta waves, short PR interval <100 msec, Wolff-Parkinson-White syndrome) on the ECG performed at the Screening Visit or before the test dose administration;
8. Evidence of a second- or third-degree AV block on the ECG performed at the Screening Visit or before the test dose administration;
9. History or evidence of severe ventricular arrhythmia (e.g., torsades de pointes, ventricular fibrillation, or ventricular tachycardia);
10. Current congestive heart failure defined by the New York Heart Association Class II to IV;
11. History of Acute Coronary Syndrome or stroke within 6 months of Screening;
12. Evidence of hepatic dysfunction defined as alanine aminotransferase or aspartate aminotransferase >3 × the upper limit of normal (ULN) or total bilirubin >2 × ULN at the Screening Visit, unless due to Gilbert syndrome;
13. Evidence of End-Stage Renal Disease as determined by an estimated glomerular filtration rate assessed at the Screening Visit of <15 mL/min/1.73m2, or requiring hemodialysis;
14. Females who are pregnant or lactating;
15. Evidence or history of any significant physical or psychiatric condition including drug abuse, which, in the opinion of the Investigator, could jeopardize the safety of patients or affect their participation in the study. Additionally, the Investigator has the ability to exclude a patient if for any reason the Investigator judges the patient is not a good candidate for the study or will not be able to follow study procedures;
16. Participation in any investigational drug or device study or the use of any investigational drug or device within 30 days of the Screening Visit; or
17. Previously enrolled in a clinical trial for etripamil and received study drug during a perceived
episode of PSVT.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of the RAPID study is to determine whether Etripamil nasal spray (NS) self-administered by patients is superior to placebo at terminating episodes of PSVT in an at-home setting.;Secondary Objective: The secondary objective of this study is to evaluate the safety of Etripamil when self administered by patients without medical supervision.;Primary end point(s): The primary efficacy endpoint is defined as time to an adjudicated termination of a positively<br>adjudicated episode of PSVT and conversion to SR for at least 30 seconds within 30 minutes of<br>start of study drug dosing.;Timepoint(s) of evaluation of this end point: The primary efficacy endpoint will be evaluated using the time to conversion of an episode of<br>PSVT to SR after start of study drug administration as the primary efficacy variable.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Study secondary Endpoints are the Sensitivity estimators, and are defined in the statistical analysis plan, and details are in the protocol v7.0 section 9.2.4.;Timepoint(s) of evaluation of this end point: Please see above