Efficacy and Safety of Intranasal MSP-2017 (Etripamil) for the Conversion of PSVT to Sinus Rhythm
Condition: Paroxysmal Supraventricular Tachycardia (PSVT)
MeSH terms: Tachycardia; Tachycardia, Supraventricular; Tachycardia, Ventricular
Intervention: Etripamil; Placebo
Intervention description: intranasal administration via 4 prefilled Aptar Pharma Unit-Dose Spray devices; intranasal administration via 4 prefilled Aptar Pharma Unit-Dose Spray devices
Intervention MeSH terms: Etripamil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking description: If, during the double-blind study, PSVT could not be induced, the mechanism of PSVT was neither atrioventricular (AV) reentrant tachycardia (AVRT) nor AV nodal reentrant tachycardia (AVNRT), or it was not possible to sustain an episode of PSVT for 5 minutes in a subject who previously provided written informed consent for substudy participation, the subject was eligible to participate in the optional open-label substudy.
Enrollment: 199.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to demonstrate the superiority of at least 1 dose of
      intranasal (IN) MSP-2017 (Etripamil) over placebo in terminating PSVT induced in an
      electrophysiology (EP) laboratory.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female, aged 18 years and older at Screening

          -  Has a history of PSVT

          -  Is scheduled for an electrophysiology study and catheter ablation

          -  Has provided written informed consent

          -  Agrees to use a medically accepted form of contraception or abstinence to prevent
             pregnancy. Males must agree to use an acceptable form of contraception or abstinence
             from the time of study drug administration through the Follow-up Visit. Females must
             agree to use an acceptable form of contraception or abstinence from Screening until 30
             days following study drug administration. Post-menopausal female subjects must be
             amenorrheic for ≥ 12 months prior to Screening or ≥ 6 weeks post-surgical bilateral
             oophorectomy (with or without hysterectomy) prior to Screening, if they do not wish to
             use an acceptable form of contraception or abstinence. Acceptable forms of
             contraception include: A condom and an intrauterine device; A condom and hormonal
             contraception; A condom and a diaphragm; Sterilization of the subject or the subject's
             partner(s) (sterilization procedure must have been performed 3 or more months prior);
             Hysterectomy of the subject or the subject's partner(s)

          -  If a female of childbearing potential: Has a negative serum pregnancy test result at
             Screening (Screening must occur ≥7 days prior to randomization [ie, on or before Day
             -7]) and at the Treatment Visit (pre-PSVT induction); Has had a menstrual period
             within 28 days of the Treatment Visit.

        Exclusion Criteria:

          -  Has a history of serious allergic reaction to verapamil (especially when administered
             intravenously) including rash, itching or swelling (especially of the face, tongue, or
             throat), severe dizziness, or trouble breathing

          -  Is currently participating in another drug or device study, or has received an
             investigational drug or device within 30 days of Screening

          -  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 subject or impact the validity of study results

          -  Is a female who is breast feeding, pregnant, or planning to become pregnant during the
             study period

          -  Has evidence of any clinically significant acute or chronic condition of the nasal
             cavity (e.g., rhinitis or deviated septum) which could interfere with IN
             administration of the study drug in either or both nasal cavities

          -  Has any of the following at screening or at the Treatment Visit: Systolic blood
             pressure <100 mmHg, Diastolic blood pressure <50 mmHg

          -  Has evidence of hepatic impairment, defined as: Alanine aminotransferase or aspartate
             aminotransferase levels that are greater than or equal to 3× upper limit of normal
             (ULN) or Bilirubin levels that are greater than or equal to 2× ULN, unless due to
             Gilbert's syndrome

          -  Has evidence of renal impairment, defined as an estimated glomerular filtration rate
             <30 mL/min (Modification of Diet in Renal Disease method)

          -  Has taken digoxin, verapamil, diltiazem, or any Class I, II (e.g., beta blockers), or
             III antiarrhythmic drug less than the equivalent of 5 half-lives of this drug prior to
             the Treatment Visit

          -  Has taken amiodarone within 30 days of the Treatment Visit

          -  Has taken drugs of abuse which, in the opinion of the Investigator, would impact the
             validity of study results

          -  Has had myocardial infarction, percutaneous coronary intervention, cerebrovascular
             accident, transient ischemic attack, unstable angina, or acute decompensation of heart
             failure within 6 months of Screening

          -  Has a history or evidence of second- or third-degree atrioventricular block

          -  Has an implanted device (e.g., pacemaker, or implantable cardioverter defibrillator)
             that precludes study participation in the opinion of the Investigator and Study
             Medical Monitor

          -  Has a history or evidence of preexcitation syndrome (e.g., Wolff-Parkinson- White
             syndrome, short PR, etc.)

          -  Has evidence of a QT interval (Bazett's correction) (QTcB) >455 milliseconds at
             Screening or at the Treatment Visit

          -  Has a history or evidence of familial long QT syndrome, torsades de pointes,
             ventricular fibrillation, sustained ventricular tachycardia, Brugada syndrome, or
             sudden cardiac death

          -  Has evidence of recurrent or chronic atrial tachycardia, atrial flutter, or atrial
             fibrillation; that could interfere with the current investigation; or

          -  Has a history or evidence of congestive heart failure (except New York Heart
             Association Class I) or pulmonary edema

        In addition, randomized subjects who meet any of the following criteria at the Treatment
        Visit (Day 1) prior to study drug administration, will be excluded from participation in
        the study:

          -  PSVT cannot be induced or the mechanism of PSVT is neither Atrioventricular reentrant
             tachycardia (AVRT) nor Atrioventricular nodal reentry tachycardia (AVNRT)

          -  It is not possible to sustain an episode of PSVT for 5 minutes

          -  The subject requires a continuous sedative (e.g., propofol), continuous analgesic, or
             inhaled anesthetic at any point until time 30. Minimally necessary dose(s) of
             benzodiazepine(s) (e.g., midazolam) and/or narcotic(s) (e.g., fentanyl) (given via
             single or multiple administration[s]) may be used at the Investigator's discretion.
             The identity(-ies) and actual administered dose(s) of any benzodiazepine(s) and/or
             narcotic(s) should be recorded in the study documentation. Local anesthetic(s) may be
             used at the Investigator's discretion; any use should be recorded in the study
             documentation

          -  The subject has undergone prior ablation, and the subject's atrioventricular node
             function is abnormal in the opinion of the Investigator