Drug-induced Surface ECG ChangesPhase 1NCT01873950

Study of the Electrocardiographic Effects of Ranolazine, Dofetilide, Verapamil, and Quinidine in Healthy Subjects

A Phase 1 study testing Ranolazine, Dofetilide and Verapamil in people with Drug-induced Surface ECG Changes, run by Food and Drug Administration (FDA).

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 35 yearsHealthy volunteers can take part
Conditions the study is for: Drug-induced Surface ECG Changes
What is being tested?: Ranolazine, Dofetilide and Verapamil
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 22 participants
Where: No sites listed yet
Study dates: May 2013to Dec 2014
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 35 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

None listed.

Who cannot join

Subjects who meet any of the following exclusion criteria will not be eligible to participate in the study:
Subject has a 12 lead safety ECG result at Screening or Check in of Period 1 with evidence of any of the following abnormalities:
QTc using Fridericia correction (QTcF) >450 milliseconds (ms) for men and >470 ms for women
PR interval >220 ms
QRS duration >110 ms
Second- or third-degree atrioventricular block

Show all 32Show fewer

Complete left or right bundle branch block or incomplete right bundle branch block
Heart rate <40 or >90 beats per minute
Pathological Q-waves (defined as Q wave >40 ms)
Ventricular pre-excitation
Subject has more than 12 to 20 ectopic beats during the 3 hour Holter ECG at Screening.
Subject has a history of unexplained syncope, structural heart disease, long QT syndrome, heart failure, myocardial infarction, angina, unexplained cardiac arrhythmia, torsades de pointes, ventricular tachycardia, or placement of a pacemaker or implantable defibrillator. Subjects will also be excluded if there is a family history of long QT syndrome (genetically proven or suggested by sudden death of a close relative due to cardiac causes at a young age) or Brugada syndrome.
Subject has a history or current evidence of any clinically significant (as determined by the investigator) cardiovascular, dermatologic, endocrine, gastrointestinal, hematologic, hepatic, immunologic, metabolic, neurologic, psychiatric, pulmonary, renal, urologic, and/or other major disease or malignancy (excluding nonmelanoma skin cancer). The investigator may allow exceptions to these criteria (e.g., stable mild joint disease [that will not interfere with or influence the leg raises/exercises required by the protocol, in the opinion of the investigator], cholecystectomy, childhood asthma) following discussion with the medical monitor.
Subject has a history of thoracic surgery.
Subject has any condition possibly affecting study drug absorption (e.g., gastrectomy, Crohn's disease, irritable bowel syndrome).
Subject has a skin condition likely to compromise ECG electrode placement.
Subject is a female with breast implants.
Subject's laboratory test results at Screening or Check in of Period 1 are outside the reference ranges provided by the clinical laboratory and considered clinically significant (as determined and documented by the investigator or designee).
Subject's laboratory test results at Screening or Check in of Period 1 indicate hypokalemia, hypocalcemia, or hypomagnesemia according to lower limits of the reference ranges provided by the clinical laboratory.
Subject's laboratory test results at Screening or Check in of Period 1 are >2 × the upper limit of normal (ULN) for alanine aminotransferase or aspartate aminotransferase, >1.5 × ULN for bilirubin, or >1.5 × ULN for creatinine.
Subject has a positive test result at Screening for human immunodeficiency virus antibody, hepatitis C antibodies, or hepatitis B surface antigen.
Subject has a mean systolic blood pressure <90 or >140 mmHg or a mean diastolic blood pressure <50 or >90 mmHg at either Screening or Check in of Period 1. Blood pressure will be measured in triplicate after the subject has been resting in a supine position for a minimum of 5 minutes.
Subject has a known hypersensitivity to ranolazine, dofetilide, verapamil, or quinidine or related compounds.
Subject has consumed alcohol, xanthine containing products (e.g., tea, coffee, chocolate, cola), caffeine, grapefruit, or grapefruit juice within 48 hours before dosing or anticipates an inability to abstain from these products throughout the duration of the study.
Subject has used nicotine containing products (e.g., cigarettes, cigars, chewing tobacco, snuff) within 6 weeks before Screening (self reported).
Subject is unable to tolerate a controlled, quiet study conduct environment, including avoidance of music, television, movies, games, and activities that may cause excitement, emotional tension, or arousal during the prespecified time points (e.g., before and during ECG extraction windows).
Subject is unwilling to comply with study rules, including the study specific diet, attempting to void at specified times (e.g., before ECG extraction windows), remaining quiet, awake, undistracted, motionless, and supine during specified times, and avoiding vigorous exercise as directed.
Subject has a history of consuming more than 14 units of alcoholic beverages per week within 6 months before Screening, has a history of alcoholism or drug/chemical/substance abuse within 2 years before Screening (Note: 1 unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits/hard liquor), or has a positive test result for alcohol or drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, and opiates) at Screening or Check in of each period.
Subject has used any prescription or nonprescription drugs within 14 days or 5 half lives (whichever is longer), or complementary and alternative medicines within 28 days before the first dose of study drug (excluding oral contraceptives, hormone replacement therapy, aspirin, ibuprofen, and acetaminophen).
Subject is currently participating in another clinical study of an investigational drug or has been treated with any investigational drug within 30 days or 5 half lives (whichever is longer) of the compound.
Subject has had any significant blood loss, donated 1 unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days, or donated plasma within 7 days before Check in of Period 1.
Subject has any other condition that precludes his or her participation in the study (as determined by the investigator).

About this study

Official title: A Double-Blind, Randomized, Placebo-Controlled Single-Dose, Five Period Crossover Study of the Electrocardiographic Effects of Ranolazine, Dofetilide, Verapamil, and Quinidine in Healthy Subjects

This study seeks to compare 4 known QT prolonging drugs versus placebo to determine their effects on electrophysiological and other clinical parameters. The underlying purpose is to determine if depolarization and repolarization effects caused by drugs with differing ionic channel mechanisms can be distinguished from one another, and to gauge the sensitivity and specificity of novel signal analyses for detection of depolarization and repolarization changes. Secondarily, to evaluate the exposure response relationship and drug induced effects on the heart rate biomarker relationship.

Read the detailed description

This will be a randomized, double blind, 5 way crossover research study in healthy male and female subjects, 18 to 35 years of age, to compare 4 known QT prolonging drugs versus placebo to determine their effects on electrophysiological and other clinical parameters. To maintain the study blind, subjects will be blindfolded during study drug administration. The cardiologists at the central ECG laboratory (Spaulding Clinical Research, LLC) will be blinded to treatment, time, and study day/subject identifiers.

Subjects who meet all of the following inclusion criteria will be eligible to participate in the study:

Subject signs an Institutional Review Board (IRB) approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act [HIPAA] authorization for sites in the United States) before any study related procedures are performed.
Subject is a healthy man or woman, 18 to 35 years of age, inclusive, who weighs at least 50 kg (110 pounds) and has a body mass index of 18 to 27 kg/m2, inclusive, at Screening.
Subject has normal medical history findings, clinical laboratory results, vital sign measurements, 12 lead ECG results, and physical examination findings at Screening or, if abnormal, the abnormality is not considered clinically significant (as determined and documented by the investigator or designee).
Female subjects must be at least 2 years postmenopausal, surgically sterile or practicing 2 highly effective methods of birth control (as determined by the investigator or designee; one of the methods must be a barrier technique), and not pregnant or lactating before enrollment in the study.
Male or female subjects must agree to practice 2 highly effective methods of birth control (as determined by the investigator or designee; one of the methods must be a barrier technique) from Screening until 30 days after the last dose of study drug.
Subject is highly likely (as determined by the investigator) to comply with the protocol-defined procedures and to complete the study.

Conditions: Drug-induced Surface ECG Changes
Being tested: Ranolazine, Dofetilide, Verapamil, Quinidine sulfate, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RanolazineDrug
DofetilideDrug
VerapamilDrug
Quinidine sulfateDrug
PlaceboDrug

Study groups in NCT01873950
Study group	Role	What they receive
Ranolazine 1500mg	Experimental	Ranolazine Receives: Drug: Ranolazine
Dofetilide 500mcg	Experimental	Dofetilide Receives: Drug: Dofetilide
Verapamil HCl 120 mg	Experimental	Verapamil Receives: Drug: Verapamil
Quinidine sulfate 400mg	Experimental	Quinidine sulfate Receives: Drug: Quinidine sulfate
Placebo	Placebo comparator	Placebo Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Placebo, and Baseline-adjusted Changes in PR, QRS, J-Tpeak, Tpeak-Tend and QTc
Compute maximum mean placebo, and baseline-adjusted change for: PR (ms), QRS (ms), J-Tpeak (ms), Tpeak-Tend (ms) and QTc (ms)
Measured: 24 hours
Placebo, and Baseline-adjusted Changes in Spatial QRS-T Angle
Compute maximum mean placebo, and baseline-adjusted change for: spatial QRS-T angle (degrees)
Measured: 24 hours
Placebo, and Baseline-adjusted Changes in Ventricular Gradient
Compute maximum mean placebo, and baseline-adjusted change for: ventricular gradient (mV*ms).
Measured: 24 hours

Secondary outcomes (7)

Change in Relationship (Ratio) Between Heart Rate and QT
Different post-dose time-points employ different techniques for altering heart rate (leg raises and postural maneuvers). Using the measurements from all the time-points of postural maneuvers, the QT/RR relationship was modeled as a linear relationship between the square root of RR in seconds and QT in seconds and computed on a by subject, treatment and time-point basis. The change in the QT and heart rate relationship was assessed as the difference (mean and 95% CI) between the slopes from the models for each drug vs. placebo.
Measured: 24 hours
Change in PR, QRS, J-Tpeak, Tpeak-Tend and QTc Using Exposure/Response (Dofetilide and Verapamil Arms)
The exposure response analysis will be performed for each treatment and will use a linear or nonlinear model (as determined by visual inspection) to quantify the relationship between exposure and Baseline and placebo adjusted change from Baseline for each ECG parameter (same as for primary analysis).
The magnitude of change (mean and 95% CI) in QTc for the observed mean Cmax for each drug may be calculated.
Measured: 24 hours
Change in PR, QRS, J-Tpeak, Tpeak-Tend and QTc Using Exposure/Response (Ranolazine and Quinidine Arms)
The exposure response analysis will be performed for each treatment and will use a linear or nonlinear model (as determined by visual inspection) to quantify the relationship between exposure and Baseline and placebo adjusted change from Baseline for each ECG parameter (same as for primary analysis).
The magnitude of change (mean and 95% CI) in QTc for the observed mean Cmax for each drug may be calculated.
Measured: 24 hours
Change in Spatial QRS-T Angle Using Exposure/Response (Dofetilide and Verapamil Arms)
The exposure response analysis will be performed for each treatment and will use a linear or nonlinear model (as determined by visual inspection) to quantify the relationship between exposure and Baseline and placebo adjusted change from Baseline for each ECG parameter (same as for primary analysis).
The magnitude of change (mean and 95% CI) in spatial QRS-T angle for the observed mean Cmax for each drug may be calculated.
Measured: 24 hours
Change in Spatial QRS-T Angle Using Exposure/Response (Ranolazine and Quinidine Arms)
The exposure response analysis will be performed for each treatment and will use a linear or nonlinear model (as determined by visual inspection) to quantify the relationship between exposure and Baseline and placebo adjusted change from Baseline for each ECG parameter (same as for primary analysis).
The magnitude of change (mean and 95% CI) in spatial QRS-T angle for the observed mean Cmax for each drug may be calculated.
Measured: 24 hours
Change in Ventricular Gradient Using Exposure/Response (Dofetilide and Verapamil Arms)
The exposure response analysis will be performed for each treatment and will use a linear or nonlinear model (as determined by visual inspection) to quantify the relationship between exposure and Baseline and placebo adjusted change from Baseline for each ECG parameter (same as for primary analysis).
The magnitude of change (mean and 95% CI) in ventricular gradient for the observed mean Cmax for each drug may be calculated.
Measured: 24 hours
Change in Ventricular Gradient Using Exposure/Response (Ranolazine and Quinidine Arms)
The exposure response analysis will be performed for each treatment and will use a linear or nonlinear model (as determined by visual inspection) to quantify the relationship between exposure and Baseline and placebo adjusted change from Baseline for each ECG parameter (same as for primary analysis).
The magnitude of change (mean and 95% CI) in ventricular gradient for the observed mean Cmax for each drug may be calculated.
Measured: 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2013Dec 2014

First posted10 Jun 2013 (estimated)
Study startMay 2013
Primary completionJul 2013
Study completionDec 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (6)Papers the sponsor has linked to this study.
Other trials for Drug-induced Surface ECG ChangesStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 22 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01873950
Sponsor's protocol ID: 13-011D
Other IDs: SCR-002
Status last verified: Feb 2018
First submitted: 22 May 2013
Last updated: 8 Mar 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Johannesen L, Vicente J, Mason JW, Sanabria C, Waite-Labott K, Hong M, Guo P, Lin J, Sorensen JS, Galeotti L, Florian J, Ugander M, Stockbridge N, Strauss DG. Differentiating drug-induced multichannel block on the electrocardiogram: randomized study of dofetilide, quinidine, ranolazine, and verapamil. Clin Pharmacol Ther. 2014 Nov;96(5):549-58. doi: 10.1038/clpt.2014.155. Epub 2014 Jul 23.
PubMed 25054430
Vicente J, Johannesen L, Mason JW, Crumb WJ, Pueyo E, Stockbridge N, Strauss DG. Comprehensive T wave morphology assessment in a randomized clinical study of dofetilide, quinidine, ranolazine, and verapamil. J Am Heart Assoc. 2015 Apr 13;4(4):e001615. doi: 10.1161/JAHA.114.001615.
PubMed 25870186
Vicente J, Johannesen L, Mason JW, Pueyo E, Stockbridge N, Strauss DG. Sex differences in drug-induced changes in ventricular repolarization. J Electrocardiol. 2015 Nov-Dec;48(6):1081-7. doi: 10.1016/j.jelectrocard.2015.08.004. Epub 2015 Aug 4.
PubMed 26324176
Strauss DG, Vicente J, Johannesen L, Blinova K, Mason JW, Weeke P, Behr ER, Roden DM, Woosley R, Kosova G, Rosenberg MA, Newton-Cheh C. Common Genetic Variant Risk Score Is Associated With Drug-Induced QT Prolongation and Torsade de Pointes Risk: A Pilot Study. Circulation. 2017 Apr 4;135(14):1300-1310. doi: 10.1161/CIRCULATIONAHA.116.023980. Epub 2017 Feb 17.
PubMed 28213480
Vicente J, Johannesen L, Hosseini M, Mason JW, Sager PT, Pueyo E, Strauss DG. Electrocardiographic Biomarkers for Detection of Drug-Induced Late Sodium Current Block. PLoS One. 2016 Dec 30;11(12):e0163619. doi: 10.1371/journal.pone.0163619. eCollection 2016.
PubMed 28036334
Johannesen L, Vicente J, Hosseini M, Strauss DG. Automated Algorithm for J-Tpeak and Tpeak-Tend Assessment of Drug-Induced Proarrhythmia Risk. PLoS One. 2016 Dec 30;11(12):e0166925. doi: 10.1371/journal.pone.0166925. eCollection 2016.
PubMed 28036330

Study at a glance

From the registry record, last updated by the sponsor on 8 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Double-Blind, Randomized, Placebo-Controlled Single-Dose, Five Period Crossover Study of the Electrocardiographic Effects of Ranolazine, Dofetilide, Verapamil, and Quinidine in Healthy Subjects
ClinicalTrials.gov ID: NCT01873950
Acronym / sponsor ID: 13-011D
Conditions: Drug-induced Surface ECG Changes
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 22 participants (actual)
Lead sponsor: Food and Drug Administration (FDA)US federal agency
Collaborators: Spaulding Clinical Research LLC
Study start: May 2013
Primary completion: Jul 2013 (actual)
Study completion: Dec 2014 (actual)
First posted: 10 Jun 2013 (estimated)
Results: Posted 21 May 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Subjects who meet all of the following inclusion criteria will be eligible to participate in the study:

Subject signs an Institutional Review Board (IRB) approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act [HIPAA] authorization for sites in the United States) before any study related procedures are performed.
Subject is a healthy man or woman, 18 to 35 years of age, inclusive, who weighs at least 50 kg (110 pounds) and has a body mass index of 18 to 27 kg/m2, inclusive, at Screening.
Subject has normal medical history findings, clinical laboratory results, vital sign measurements, 12 lead ECG results, and physical examination findings at Screening or, if abnormal, the abnormality is not considered clinically significant (as determined and documented by the investigator or designee).
Female subjects must be at least 2 years postmenopausal, surgically sterile or practicing 2 highly effective methods of birth control (as determined by the investigator or designee; one of the methods must be a barrier technique), and not pregnant or lactating before enrollment in the study.
Male or female subjects must agree to practice 2 highly effective methods of birth control (as determined by the investigator or designee; one of the methods must be a barrier technique) from Screening until 30 days after the last dose of study drug.
Subject is highly likely (as determined by the investigator) to comply with the protocol-defined procedures and to complete the study.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 5

Arm	Type	Receives
Ranolazine 1500mg	Experimental	Drug: RanolazineRanolazine
Dofetilide 500mcg	Experimental	Drug: DofetilideDofetilide
Verapamil HCl 120 mg	Experimental	Drug: VerapamilVerapamil
Quinidine sulfate 400mg	Experimental	Drug: Quinidine sulfateQuinidine sulfate
Placebo	Placebo comparator	Drug: PlaceboPlacebo

Who may qualify

Ages: 18 to 35 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (0 listed)

Key exclusion criteria (32 listed)

Subjects who meet any of the following exclusion criteria will not be eligible to participate in the study:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Ranolazine	Drug	Ranolazine 1500mg
Dofetilide	Drug	Dofetilide 500mcg
Verapamil	Drug	Verapamil HCl 120 mg
Quinidine sulfate	Drug	Quinidine sulfate 400mg
Placebo	Drug	Placebo

Primary outcome

Placebo, and Baseline-adjusted Changes in PR, QRS, J-Tpeak, Tpeak-Tend and QTc
Time frame: 24 hours
Compute maximum mean placebo, and baseline-adjusted change for: PR (ms), QRS (ms), J-Tpeak (ms), Tpeak-Tend (ms) and QTc (ms)
Placebo, and Baseline-adjusted Changes in Spatial QRS-T Angle
Time frame: 24 hours
Compute maximum mean placebo, and baseline-adjusted change for: spatial QRS-T angle (degrees)
Placebo, and Baseline-adjusted Changes in Ventricular Gradient
Time frame: 24 hours
Compute maximum mean placebo, and baseline-adjusted change for: ventricular gradient (mV*ms).

7 secondary outcomes

Change in Relationship (Ratio) Between Heart Rate and QT
Time frame: 24 hours
Change in PR, QRS, J-Tpeak, Tpeak-Tend and QTc Using Exposure/Response (Dofetilide and Verapamil Arms)
Time frame: 24 hours
Change in PR, QRS, J-Tpeak, Tpeak-Tend and QTc Using Exposure/Response (Ranolazine and Quinidine Arms)
Time frame: 24 hours
Change in Spatial QRS-T Angle Using Exposure/Response (Dofetilide and Verapamil Arms)
Time frame: 24 hours
Change in Spatial QRS-T Angle Using Exposure/Response (Ranolazine and Quinidine Arms)
Time frame: 24 hours
Change in Ventricular Gradient Using Exposure/Response (Dofetilide and Verapamil Arms)
Time frame: 24 hours
Change in Ventricular Gradient Using Exposure/Response (Ranolazine and Quinidine Arms)
Time frame: 24 hours

Results and safety

Results posted to the registry on 21 May 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ranolazine 1500 mg	5	5
Dofetilide 500 mcg	4	4
Verapamil HCl 120 mg	5	5
Quinidine Sulfate 400 mg	4	4
Placebo	4	4

Primary outcome: Placebo, and Baseline-adjusted Changes in PR, QRS, J-Tpeak, Tpeak-Tend and QTc

Time frame: 24 hours. Least squares mean (95% Confidence Interval). Unit: ms

Measure	Ranolazine 1500mg n = 22	Dofetilide 500mcg n = 22	Verapamil HCl 120 mg n = 22	Quinidine Sulfate 400mg n = 21
Change in PR interval	6.5 (1.1 to 11.8)	2.3 (-3.0 to 7.6)	32.1 (26.7 to 37.4)	5.1 (-0.3 to 10.5)
Change in QRS duration	2.7 (0.5 to 4.9)	1.1 (-1.1 to 3.3)	2.6 (0.4 to 4.8)	2.1 (-0.2 to 4.3)
Change in J-Tpeakc	3.3 (-3.4 to 9.9)	39.5 (32.8 to 46.2)	-2.4 (-9.0 to 4.3)	29.1 (22.4 to 35.9)
Change in Tpeak-Tend	8.8 (1.9 to 15.8)	40.0 (33.0 to 46.9)	4.8 (-2.2 to 11.7)	49.8 (42.8 to 56.8)
Change in QTc	12.6 (5.5 to 19.6)	79.3 (72.2 to 86.3)	5.2 (-1.8 to 12.2)	78.1 (70.9 to 85.2)

Ranolazine 1500mg vs Dofetilide 500mcg vs Verapamil HCl 120 mg vs Quinidine Sulfate 400mg: p <0.05, Mixed Models Analysis

Primary outcome: Placebo, and Baseline-adjusted Changes in Spatial QRS-T Angle

Time frame: 24 hours. Least squares mean (95% Confidence Interval). Unit: degrees

Measure	Ranolazine 1500mg n = 22	Dofetilide 500mcg n = 22	Verapamil HCl 120 mg n = 22	Quinidine Sulfate 400mg n = 21
Value	-2.2 (-4.6 to 0.1)	-4.9 (-7.2 to -2.6)	-2.4 (-4.4 to 0.3)	3.9 (1.6 to 6.3)

Ranolazine 1500mg vs Dofetilide 500mcg vs Verapamil HCl 120 mg vs Quinidine Sulfate 400mg: p <0.05, Mixed Models Analysis

Primary outcome: Placebo, and Baseline-adjusted Changes in Ventricular Gradient

Time frame: 24 hours. Least squares mean (95% Confidence Interval). Unit: mV*ms

Measure	Ranolazine 1500mg n = 22	Dofetilide 500mcg n = 22	Verapamil HCl 120 mg n = 22	Quinidine Sulfate 400mg n = 21
Value	2.5 (-1.8 to 6.8)	4.8 (0.5 to 9.1)	4.2 (-0.1 to 8.5)	6.0 (1.6 to 10.3)

Ranolazine 1500mg vs Dofetilide 500mcg vs Verapamil HCl 120 mg vs Quinidine Sulfate 400mg: p <0.05, Mixed Models Analysis

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: From May 2013 to July 2013. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ranolazine 1500mg	0 of 22 (0%)	4 of 22 (18.2%)	Not reported
Dofetilide 500mcg	0 of 22 (0%)	6 of 22 (27.3%)	Not reported
Verapamil HCl 120 mg	0 of 22 (0%)	6 of 22 (27.3%)	Not reported
Quinidine Sulfate 400mg	0 of 21 (0%)	12 of 21 (57.1%)	Not reported
Placebo	0 of 22 (0%)	3 of 22 (13.6%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 25054430Johannesen L, Vicente J, Mason JW, Sanabria C, Waite-Labott K, Hong M, Guo P, Lin J, Sorensen JS, Galeotti L, Florian J, Ugander M, Stockbridge N, Strauss DG. Differentiating drug-induced multichannel block on the electrocardiogram: randomized study of dofetilide, quinidine, ranolazine, and verapamil. Clin Pharmacol Ther. 2014 Nov;96(5):549-58. doi: 10.1038/clpt.2014.155. Epub 2014 Jul 23.
Results publication: PubMed 25870186Vicente J, Johannesen L, Mason JW, Crumb WJ, Pueyo E, Stockbridge N, Strauss DG. Comprehensive T wave morphology assessment in a randomized clinical study of dofetilide, quinidine, ranolazine, and verapamil. J Am Heart Assoc. 2015 Apr 13;4(4):e001615. doi: 10.1161/JAHA.114.001615.
Results publication: PubMed 26324176Vicente J, Johannesen L, Mason JW, Pueyo E, Stockbridge N, Strauss DG. Sex differences in drug-induced changes in ventricular repolarization. J Electrocardiol. 2015 Nov-Dec;48(6):1081-7. doi: 10.1016/j.jelectrocard.2015.08.004. Epub 2015 Aug 4.
Derived from this study: PubMed 28213480Strauss DG, Vicente J, Johannesen L, Blinova K, Mason JW, Weeke P, Behr ER, Roden DM, Woosley R, Kosova G, Rosenberg MA, Newton-Cheh C. Common Genetic Variant Risk Score Is Associated With Drug-Induced QT Prolongation and Torsade de Pointes Risk: A Pilot Study. Circulation. 2017 Apr 4;135(14):1300-1310. doi: 10.1161/CIRCULATIONAHA.116.023980. Epub 2017 Feb 17.
Derived from this study: PubMed 28036334Vicente J, Johannesen L, Hosseini M, Mason JW, Sager PT, Pueyo E, Strauss DG. Electrocardiographic Biomarkers for Detection of Drug-Induced Late Sodium Current Block. PLoS One. 2016 Dec 30;11(12):e0163619. doi: 10.1371/journal.pone.0163619. eCollection 2016.
Derived from this study: PubMed 28036330Johannesen L, Vicente J, Hosseini M, Strauss DG. Automated Algorithm for J-Tpeak and Tpeak-Tend Assessment of Drug-Induced Proarrhythmia Risk. PLoS One. 2016 Dec 30;11(12):e0166925. doi: 10.1371/journal.pone.0166925. eCollection 2016.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Carlos Sanabria, MD principal investigator

Spaulding Clinical Research LLC

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ranolazine, Dofetilide and Verapamil in people with Drug-induced Surface ECG Changes, run by Food and Drug Administration (FDA).

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 0 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Placebo, and Baseline-adjusted Changes in PR, QRS, J-Tpeak, Tpeak-Tend and QTc (time frame: 24 hours). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01873950, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2018.