Clinical trial NCT02296190: Efficacy and Safety of Intranasal MSP-2017 (Etripamil) for the Conversion of PSVT to Sinus Rhythm
Official title: Multi-Center, Placebo-Controlled, Dose-Ranging Phase 2 Electrophysiological Study of Intranasal Administration of MSP-2017 for the Conversion of Induced Paroxysmal Supraventricular Tachycardia (PSVT) to Sinus Rhythm
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Paroxysmal Supraventricular Tachycardia (PSVT)
Lead sponsor: Milestone Pharmaceuticals Inc.
Sponsor class: OTHER
Collaborators: name: Medpace, Inc.
First posted: 2014-11-20
Enrollment: 199
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: This is a multi-center, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the effects of 4 different doses of MSP-2017 (Etripamil) in subjects with paroxysmal supraventricular tachycardia. It includes an up to 21-day Screening Period, a 1-day Treatment Visit, and either a Follow-up Visit or Early Termination Visit occurring 12 hours to 5 days after the Treatment Visit. Subjects will be randomized to yield at least 100 evaluable subjects distributed into 5 groups of at least 20 subjects each.

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

Primary outcomes:
measure: The Percentage of Subjects Successfully Converted From PSVT to Sinus Rhythm Within 15 Minutes of Study Drug Administration
timeFrame: Within 15 minutes of study drug administration
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Heart Rhythm Center
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Sacramento
country: United States
facility: Mercy General Hospital
state: California
city: Littleton
country: United States
facility: South Denver Cardiology Associates
state: Colorado
city: Washington
country: United States
facility: Medstar Washington Hospital Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Memorial Hospital Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Saint Petersburg
country: United States
facility: Northside Hospital
state: Florida
city: Tampa
country: United States
facility: University of South Florida Health South Tampa Center
state: Florida
city: Atlanta
country: United States
facility: Piedmont Atlanta Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: West Des Moines
country: United States
facility: Iowa Heart Center
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: MedStar Health Research Institute
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Canton
country: United States
facility: Aultman Hospital Cardiology Clinical Trials
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center Division of Cardiovascular Diseases
state: Ohio
city: Toledo
country: United States
facility: ProMedica Toledo Hospital
state: Ohio
city: Willoughby
country: United States
facility: Great Lakes Medical Research, LLC
state: Ohio
city: Rapid City
country: United States
facility: Black Hills Cardiovascular Research
state: South Dakota
city: Austin
country: United States
facility: Texas Cardiac Arrhythmia Research Foundation
state: Texas
city: Houston
country: United States
facility: Baylor St. Luke's Hospital
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
city: Lynchburg
country: United States
facility: Centra Stroobants Cardiovascular Center
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Center
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Montreal
country: Canada
facility: The Montreal Heart Institute
state: Quebec
city: Montreal
country: Canada
facility: CHUM Hotel Dieu
state: Quebec
Study officials:
affiliation: Chief Medical Officer
name: Francis Plat
role: STUDY_DIRECTOR
References:
citation: Stambler BS, Dorian P, Sager PT, Wight D, Douville P, Potvin D, Shamszad P, Haberman RJ, Kuk RS, Lakkireddy DR, Teixeira JM, Bilchick KC, Damle RS, Bernstein RC, Lam WW, O'Neill G, Noseworthy PA, Venkatachalam KL, Coutu B, Mondesert B, Plat F. Etripamil Nasal Spray for Rapid Conversion of Supraventricular Tachycardia to Sinus Rhythm. J Am Coll Cardiol. 2018 Jul 31;72(5):489-497. doi: 10.1016/j.jacc.2018.04.082.