Efficacy and Safety of Intranasal MSP-2017 (Etripamil) fo... | NCT02296190 | Trialant
NCT02296190
Sponsor
Milestone Pharmaceuticals Inc.
Status
Completed
Last Update Posted
Dec 30, 2020Actual
Enrollment
199Actual
Phase
Phase 2
Conditions
Paroxysmal Supraventricular Tachycardia (PSVT)
Interventions
Etripamil
Placebo
Countries
United States
Canada
Protocol Section
Identification Module
NCT ID
NCT02296190
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
MSP-2017-1109
Secondary IDs
Not provided
Brief Title
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
Acronym
NODE-1
Organization
Milestone Pharmaceuticals Inc.OTHER
Status Module
Record Verification Date
Dec 2020
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Mar 27, 2015
Primary Completion Date
Dec 2016Actual
Completion Date
Dec 2016Actual
First Submitted Date
Nov 18, 2014
First Submission Date that Met QC Criteria
Nov 19, 2014
First Posted Date
Nov 20, 2014Estimated
Results Waived
Not provided
Results First Submitted Date
Aug 12, 2020
Results First Submitted that Met QC Criteria
Dec 4, 2020
Results First Posted Date
Dec 30, 2020Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Mar 18, 2019
Certification/Extension First Submitted that Passed QC Review
Mar 26, 2019
Certification/Extension First Posted Date
Mar 29, 2019Actual
Last Update Submitted Date
Dec 4, 2020
Last Update Posted Date
Dec 30, 2020Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Milestone Pharmaceuticals Inc.OTHER
Collaborators
Name
Class
Medpace, Inc.
INDUSTRY
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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.
Conditions Module
Conditions
Paroxysmal Supraventricular Tachycardia (PSVT)
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
199Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Etripamil
Experimental
1 dose of Etripamil via 4 intranasal applications at time 0 (140 mg, 105 mg, 70 mg, or 35 mg)
Drug: Etripamil
Placebo
Placebo Comparator
1 dose of placebo via 4 intranasal applications at time 0
Drug: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Etripamil
Drug
intranasal administration via 4 prefilled Aptar Pharma Unit-Dose Spray devices
Etripamil
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
The Percentage of Subjects Successfully Converted From PSVT to Sinus Rhythm Within 15 Minutes of Study Drug Administration
The primary efficacy endpoint was the rate of successful PSVT conversion to sinus rhythm lasting at least 30 seconds within 15 minutes of study drug administration after a minimum of 5 minutes in sustained PSVT.
Within 15 minutes of study drug administration
Secondary Outcomes
Not provided
Other Outcomes
Not provided
Eligibility Module
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
Adults aged 18 years and older with Paroxysmal supraventricular tachycardia (PSVT) who met the study inclusion/exclusion criteria. Study was initiated on March 27, 2015 and completed on December 8, 2016 and was performed in electro-physiology clinics in the USA and Canada.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Etripamil_140 mg
1 dose of Etripamil via 4 prefilled Aptar Pharma Unit-Dose Nasal Spray devices.
FG001
Etripamil_ 105 mg
1 dose of Etripamil via 4 prefilled Aptar Pharma Unit-Dose Nasal Spray devices.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
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.
Who Masked
ParticipantInvestigator
MSP-2017
Placebo
Drug
intranasal administration via 4 prefilled Aptar Pharma Unit-Dose Spray devices
Placebo
Phoenix
Arizona
85054
United States
Mercy General Hospital
Sacramento
California
95819
United States
South Denver Cardiology Associates
Littleton
Colorado
80120
United States
Medstar Washington Hospital Center
Washington D.C.
District of Columbia
20010
United States
Memorial Hospital Jacksonville
Jacksonville
Florida
32216
United States
Mayo Clinic Jacksonville
Jacksonville
Florida
32224
United States
Northside Hospital
St. Petersburg
Florida
33709
United States
University of South Florida Health South Tampa Center
Tampa
Florida
33606
United States
Piedmont Atlanta Hospital
Atlanta
Georgia
30309
United States
Emory University Hospital
Atlanta
Georgia
30322
United States
Iowa Heart Center
West Des Moines
Iowa
50266
United States
University of Kansas Medical Center
Kansas City
Kansas
66160
United States
MedStar Health Research Institute
Baltimore
Maryland
21237
United States
Mayo Clinic
Rochester
Minnesota
55902
United States
Aultman Hospital Cardiology Clinical Trials
Canton
Ohio
44708
United States
University of Cincinnati Medical Center Division of Cardiovascular Diseases
Cincinnati
Ohio
45267
United States
ProMedica Toledo Hospital
Toledo
Ohio
43606
United States
Great Lakes Medical Research, LLC
Willoughby
Ohio
44094
United States
Black Hills Cardiovascular Research
Rapid City
South Dakota
57701
United States
Texas Cardiac Arrhythmia Research Foundation
Austin
Texas
78705
United States
Baylor St. Luke's Hospital
Houston
Texas
77030
United States
Houston Methodist Hospital
Houston
Texas
77030
United States
University of Virginia Medical Center
Charlottesville
Virginia
22908
United States
Centra Stroobants Cardiovascular Center
Lynchburg
Virginia
24501
United States
Sentara Norfolk General Hospital
Norfolk
Virginia
23507
United States
Sunnybrook Health Sciences Center
Toronto
Ontario
M4N 3M5
Canada
St. Michael's Hospital
Toronto
Ontario
M5B 1W8
Canada
The Montreal Heart Institute
Montreal
Quebec
H1T 1C8
Canada
CHUM Hotel Dieu
Montreal
Quebec
H2W 1T8
Canada
FG002
Etripamil_70 mg
1 dose of Etripamil via 4 prefilled Aptar Pharma Unit-Dose Nasal Spray devices.
FG003
Etripamil_35 mg
1 dose of Etripamil via 4 prefilled Aptar Pharma Unit-Dose Nasal Spray devices.
FG004
Placebo
1 dose of Placebo via 4 prefilled Aptar Pharma Unit-Dose Nasal Spray devices.
FG005
Open-label Etripamil 70 mg
9 subjects were assigned to an open-label Sub-study Safety Population. Subjects participating in the open-label sub-study received intra nasal administration of 70 mg MSP-2017 (total) via 2 prefilled Aptar Pharma Unit-Dose Spray devices.
FG00035 subjects
FG00141 subjects
FG00235 subjects
FG00343 subjects
FG00436 subjects
FG0059 subjects
COMPLETED
FG00021 subjects
FG00120 subjects
FG00223 subjects
FG00320 subjects
FG00420 subjects
FG0059 subjects
NOT COMPLETED
FG00014 subjects
FG00121 subjects
FG00212 subjects
FG00323 subjects
FG00416 subjects
FG0050 subjects
Type
Comment
Reasons
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
Failure to induce PSVT
FG0006 subjects
FG00110 subjects
FG0025 subjects
FG00313 subjects
FG004
Physician Decision
FG0001 subjects
FG0011 subjects
FG0020 subjects
FG0031 subjects
FG004
Withdrawal by Subject
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
PSVT < 5 minutes
FG0005 subjects
FG0016 subjects
FG0026 subjects
FG0036 subjects
FG004
Patient was given Propofol
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0031 subjects
FG004
Patient with Atrial Tachycardia
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Blood pressure <100 after sedation
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Atrial Tachycardia induced not PSVT
FG0000 subjects
FG0011 subjects
FG0021 subjects
FG0030 subjects
FG004
Patient on antiarrhythmic medication
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Failed PSVT with mechanism of AVNRT
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Lab result not available in time
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Full analysis set (all randomized participants who received at least 1 dose of study drug)
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Etripamil_140 mg
1 dose of Etripamil via 4 prefilled Aptar Pharma Unit-Dose Nasal Spray devices.
BG001
Etripamil_105 mg
1 dose of Etripamil via 4 prefilled Aptar Pharma Unit-Dose Nasal Spray devices.
BG002
Etripamil_70 mg
1 dose of Etripamil via 4 prefilled Aptar Pharma Unit-Dose Nasal Spray devices.
BG003
Etripamil_35 mg
1 dose of Etripamil via 4 prefilled Aptar Pharma Unit-Dose Nasal Spray devices.
BG004
Placebo
1 dose of Placebo via 4 prefilled Aptar Pharma Unit-Dose Nasal Spray devices.
BG005
Open- Label Etripamil 70 mg
1 dose of Etripamil via 4 prefilled Aptar Pharma Unit-Dose Nasal Spray devices.
BG006
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00021
BG00120
BG00223
BG00320
BG00420
BG0059
BG006113
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
<=18 years
BG0000
BG0010
BG0020
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00013
BG00113
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
WHITE
Title
Measurements
BG00017
BG00114
BG002
Region of Enrollment
Number
participants
Title
Denominators
Categories
Canada
Title
Measurements
BG0004
BG0017
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
The Percentage of Subjects Successfully Converted From PSVT to Sinus Rhythm Within 15 Minutes of Study Drug Administration
The primary efficacy endpoint was the rate of successful PSVT conversion to sinus rhythm lasting at least 30 seconds within 15 minutes of study drug administration after a minimum of 5 minutes in sustained PSVT.
The efficacy analysis was based on the Evaluable Population which included all randomized subjects who were induced and sustained Supraventricular tachycardia (SVT) for 5 minutes, received the study drug, and completed the assessment of conversion to sinus rhythm.
The "Open- Label Etripamil 70 mg" group was not part of the Evaluable Population, as the subjects did not meet the criteria of having sustained Supraventricular tachycardia (SVT) for 5 minutes.
Posted
Count of Participants
Participants
Within 15 minutes of study drug administration
ID
Title
Description
OG000
Etripamil_140 mg
1 dose of Etripamil via 4 prefilled Aptar Pharma Unit-Dose Nasal Spray devices.
OG001
Etripamil_ 105 mg
1 dose of Etripamil via 4 prefilled Aptar Pharma Unit-Dose Nasal Spray devices.
OG002
Etripamil_70 mg
1 dose of Etripamil via 4 prefilled Aptar Pharma Unit-Dose Nasal Spray devices.
OG003
Etripamil_35 mg
1 dose of Etripamil via 4 prefilled Aptar Pharma Unit-Dose Nasal Spray devices.
OG004
Placebo
1 dose of Placebo via 4 prefilled Aptar Pharma Unit-Dose Nasal Spray devices.
Units
Counts
Participants
OG00021
OG00120
OG00223
OG003
Title
Denominators
Categories
Title
Measurements
OG00020
OG00115
OG00220
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
OG002
OG003
OG004
Statistical analysis was performed with the Fisher's exact test to compare the conversion rate between the MSP-2017 groups and the placebo group.
Fisher Exact
<0.05
Superiority
Time Frame
Adverse events were monitored from the time of study drug administration (Treatment Visit Day 1) until study participation completed at the Follow-up Visit which occurred from 12 hours to up to 5 days after the Treatment Visit. Maximum time frame 6 days.
Description
Not provided
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Etripamil_140 mg
1 dose of Etripamil via 4 prefilled Aptar Pharma Unit-Dose Nasal Spray devices.
0
21
0
21
20
21
EG001
Etripamil_105 mg
1 dose of Etripamil via 4 prefilled Aptar Pharma Unit-Dose Nasal Spray devices.
0
20
3
20
14
20
EG002
Etripamil_70 mg
1 dose of Etripamil via 4 prefilled Aptar Pharma Unit-Dose Nasal Spray devices.
0
23
0
23
18
23
EG003
Etripamil_35 mg
1 dose of Etripamil via 4 prefilled Aptar Pharma Unit-Dose Nasal Spray devices.
0
20
0
20
17
20
EG004
Placebo
1 dose of Placebo via 4 prefilled Aptar Pharma Unit-Dose Nasal Spray devices.
0
20
1
20
4
20
EG005
Open Label Etripamil 70 mg
1 dose of Etripamil via 4 prefilled Aptar Pharma Unit-Dose Nasal Spray devices.