Ability of Late Sodium or Calcium Current Block to Balance the ECG Effects of Potassium Current Block

• Sponsor: Food and Drug Administration (FDA) (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT02308748
• Collaborator: Spaulding Clinical Research LLC (Other)
• Enrollment: 22
• Arms: 5
• Duration (Months): 1

Study Details

Study Description

Brief Summary

The primary objective of this research study is to test the hypothesis that late sodium current blocking drugs (mexiletine or lidocaine) can attenuate the effect of hERG potassium channel blocking drugs (dofetilide) on ventricular repolarization (QTc) by shortening early repolarization (J-Tpeakc). The secondary object is to assess the ability of calcium channel block (diltiazem) to reduce the QTc prolongation associated with hERG block (moxifloxacin).

Condition or Disease	Intervention/Treatment	Phase
Drug-induced QT Prolongation; Pharmacokinetics; Pharmacodynamics	Drug: Dofetilide; Drug: Mexiletine; Drug: Lidocaine; Drug: Moxifloxacin; Drug: Diltiazem; Drug: Placebo	Phase 1

Detailed Description

This is a randomized, double-blind, 5-period crossover study in healthy male and female subjects, 18 to 35 years of age, to compare the electrophysiological response of hERG potassium channel blocking drugs with and without the addition of late sodium or calcium channel blocking drugs. The 5 treatment periods are 1) dofetilide alone, 2) mexiletine with and without dofetilide, 3) lidocaine with and without dofetilide, 4) moxifloxacin with and without diltiazem and 5) placebo. During each treatment period, 12 blood samples for pharmacokinetic measurements are obtained with matched 12-lead ECG recordings.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Five Period Crossover Study of the Ability of Late Sodium or Calcium Current Block (Mexiletine, Lidocaine, or Diltiazem) to Balance the Electrocardiographic Effects of hERG Potassium Current Block (Dofetilide or Moxifloxacin)
• Study Start Date: May 1, 2014
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Dofetilide Dofetilide alone arm	Drug: Dofetilide; 8 am: Placebo 12 pm (noon): 250 µg 5:30 pm: 250 µg; Other Names: Tikosyn
Active Comparator: Dofetilide + Mexiletine Dofetilide combined with mexiletine	Drug: Dofetilide; 8 am: Placebo 12 pm (noon): 250 µg 5:30 pm: 250 µg; Other Names: Tikosyn ; Drug: Mexiletine; 8 am: weight x 4 mg/kg 12 pm (noon): Same as at 8 am 5:30 pm: Same as at 8 am; Other Names: Mexitil
Active Comparator: Dofetilide + Lidocaine Dofetilide combined with lidocaine	Drug: Dofetilide; 8 am: Placebo 12 pm (noon): 250 µg 5:30 pm: 250 µg; Other Names: Tikosyn ; Drug: Lidocaine; 9 am : 30 µg/min per kg (loading) for 60 minutes and 10 µg/min per kg (maintenance) for 30 minutes 2 pm: 55 µg/min per kg (loading) for 60 minutes and 20 µg/min per kg (maintenance) for 30 minutes 7:30 pm: 52 µg/min per kg (loading) for 60 minutes and 20 µg/min per kg (maintenance) for 30 minutes; Other Names: Lidocaine hydrochloride
Active Comparator: Moxifloxacin + Diltiazem Moxifloxacin with and without diltiazem.	Drug: Moxifloxacin; 9 am: 5.63 mg/h per kg (loading) for 1 hour and 0.26 mg/h per kg (maintenance for 30 minutes) 2 pm: 6.14 mg/h per kg (loading) for 1 hour and 0.49 mg/h per kg (maintenance for 30 minutes) 7:30 pm: 2.23 mg/h per kg (loading) for 1 hour and 0.49 mg/h per kg (maintenance for 30 minutes); Other Names: Avelox ; Drug: Diltiazem; • 7:30 pm: 330 µg/h per kg (loading) for 60 minutes and 61 µg/h per kg (maintenance) for 30 minutes; Other Names: Diltiazem hydrochloride
Placebo Comparator: Placebo Placebo (#2 gelcap and intravenous saline)	Drug: Placebo; Placebo (#2 Gelcap or IV saline); Other Names: #2 Gelcaps or IV saline

Outcome Measures

Primary Outcome Measures

1. Change in Placebo Corrected Change From Baseline QTc and J-Tpeakc Intervals on the ECG Measured in Milliseconds When Dofetilide is Administered With Mexiletine or Lidocaine Compared to When Dofetilide is Administered Alone at Evening Dose on Treatment Day [5 weeks]

   After 3rd dose of mexiletine or lidocaine (evening dose) on treatment day when combined with dofetilide to evening dose on dofetilide alone day.

Secondary Outcome Measures

1. Change in Placebo Corrected Change From Baseline QTc Interval on the ECG Measured in Milliseconds When Moxifloxacin is Administered With Diltiazem at the Evening Dose Compared to When Moxifloxacin is Administered Alone at Afternoon Dose on Treatment Day. [5 weeks]

   Evening dose (moxifloxacin+diltiazem) versus afternoon dose (diltiazem alone).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 35 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Subject is a healthy man or woman, 18 to 35 years of age, inclusive, who weighs at least 50 kg (110 pounds), no more than 85 kg (197 pounds) and has a body mass index of 18 to 27 kg/m2, inclusive, at Screening.

2. 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).

3. 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.

Exclusion Criteria:

• 1. Subject has a 12 lead safety ECG result at Screening or Check in of Period 1 with evidence of any of the following abnormalities:

• QT corrected interval (QTc) using Fridericia correction (QTcF) >430 milliseconds (ms)

• PR interval >220 ms or <120 ms

• QRS duration >110 ms

• Second- or third-degree atrioventricular block

• Complete left or right bundle branch block or incomplete right bundle branch block

• Heart rate <50 or >90 beats per minute

• Pathological Q-waves (defined as Q wave >40 ms)

• Ventricular pre-excitation

1. Subject has more than 12 ectopic beats during the 3 hour Holter ECG at Screening.

2. 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.

3. 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 activities required by the protocol, in the opinion of the investigator], cholecystectomy, childhood asthma) following discussion with the medical monitor.

4. Subject has a history of thoracic surgery.

5. Subject has any condition possibly affecting study drug absorption (e.g., gastrectomy, Crohn's disease, irritable bowel syndrome).

6. Subject has a skin condition likely to compromise ECG electrode placement.

7. Subject is a female with breast implants.

8. 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).

9. 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.

10. 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.

11. Subject has a positive test result at Screening for human immunodeficiency virus, hepatitis C antibodies, or hepatitis B surface antigen.

12. 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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Food and Drug Administration (FDA)
• Spaulding Clinical Research LLC

Investigators

• Principal Investigator: Carlos Sanabria, MD, Spaulding Clinical

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Food and Drug Administration (FDA)
• ClinicalTrials.gov Identifier: NCT02308748
• Other Study ID Numbers: 14-022D; SCR-003
• First Posted: Dec 4, 2014
• Last Update Posted: Jun 8, 2016
• Last Verified: Jun 1, 2016

• Additional relevant MeSH terms: Long QT Syndrome; Moxifloxacin; Lidocaine; Mexiletine; Dofetilide; Diltiazem

Study Results

Participant Flow

Pre-assignment Detail	44 healthy volunteers were assessed for eligibility. 15 subjects were excluded because they did not meet the inclusion criteria. 22 of 29 subjects who met the inclusion criteria were randomized and allocated to receive crossed-over intervention. Williams Latin square design balanced for first-order carryover effects was used for randomization.

Arm/Group Title	A-D-E-C-B	B-C-E-D-A	C-D-B-A-E	D-C-A-B-E	E-A-B-D-C	D-A-C-E-B	E-B-A-C-D	A-E-D-B-C	B-E-C-A-D	C-B-D-E-A
Arm/Group Description	All subjects received the same 5 treatments, separated by 6 days of washout, but were randomized to receive them in different orders. Subjects in this arm received them in the following order: Treatment A (dofetilide) Treatment D (moxifloxacin + diltiazem) Treatment E (placebo) Treatment C (dofetilide + mexiletine) Treatment B (dofetilide + lidocaine)	All subjects received the same 5 treatments, separated by 6 days of washout, but were randomized to receive them in different orders. Subjects in this arm received them in the following order: Treatment B (dofetilide + lidocaine) Treatment C (dofetilide + mexiletine) Treatment E (placebo) Treatment D (moxifloxacin + diltiazem) Treatment A (dofetilide)	All subjects received the same 5 treatments, separated by 6 days of washout, but were randomized to receive them in different orders. Subjects in this arm received them in the following order: Treatment C (dofetilide + mexiletine) Treatment D (moxifloxacin + diltiazem) Treatment B (dofetilide + lidocaine) Treatment A (dofetilide) Treatment E (placebo)	All subjects received the same 5 treatments, separated by 6 days of washout, but were randomized to receive them in different orders. Subjects in this arm received them in the following order: Treatment D (moxifloxacin + diltiazem) Treatment C (dofetilide + mexiletine) Treatment A (dofetilide) Treatment B (dofetilide + lidocaine) Treatment E (placebo)	All subjects received the same 5 treatments, separated by 6 days of washout, but were randomized to receive them in different orders. Subjects in this arm received them in the following order: Treatment E (placebo) Treatment A (dofetilide) Treatment B (dofetilide + lidocaine) Treatment D (moxifloxacin + diltiazem) Treatment C (dofetilide + mexiletine)	All subjects received the same 5 treatments, separated by 6 days of washout, but were randomized to receive them in different orders. Subjects in this arm received them in the following order: Treatment D (moxifloxacin + diltiazem) Treatment A (dofetilide) Treatment C (dofetilide + mexiletine) Treatment E (placebo) Treatment B (dofetilide + lidocaine)	All subjects received the same 5 treatments, separated by 6 days of washout, but were randomized to receive them in different orders. Subjects in this arm received them in the following order: Treatment E (placebo) Treatment B (dofetilide + lidocaine) Treatment A (dofetilide) Treatment C (dofetilide + mexiletine) Treatment D (moxifloxacin + diltiazem)	All subjects received the same 5 treatments, separated by 6 days of washout, but were randomized to receive them in different orders. Subjects in this arm received them in the following order: Treatment A (dofetilide) Treatment E (placebo) Treatment D (moxifloxacin + diltiazem) Treatment B (dofetilide + lidocaine) Treatment C (dofetilide + mexiletine)	All subjects received the same 5 treatments, separated by 6 days of washout, but were randomized to receive them in different orders. Subjects in this arm received them in the following order: Treatment B (dofetilide + lidocaine) Treatment E (placebo) Treatment C (dofetilide + mexiletine) Treatment A (dofetilide) Treatment D (moxifloxacin + diltiazem)	All subjects received the same 5 treatments, separated by 6 days of washout, but were randomized to receive them in different orders. Subjects in this arm received them in the following order: Treatment C (dofetilide + mexiletine) Treatment B (dofetilide + lidocaine) Treatment D (moxifloxacin + diltiazem) Treatment E (placebo) Treatment A (dofetilide)
Period Title: Period 1
STARTED	2	2	2	2	2	3	2	2	2	3
COMPLETED	2	2	1	2	2	3	2	2	2	3
NOT COMPLETED	0	0	1	0	0	0	0	0	0	0
Period Title: Period 1
STARTED	2	2	1	2	2	3	2	2	2	3
COMPLETED	2	2	1	2	2	3	2	1	2	3
NOT COMPLETED	0	0	0	0	0	0	0	1	0	0
Period Title: Period 1
STARTED	2	2	1	2	2	3	2	1	2	3
COMPLETED	2	2	1	2	2	3	2	1	2	2
NOT COMPLETED	0	0	0	0	0	0	0	0	0	1
Period Title: Period 1
STARTED	2	2	1	2	2	3	2	1	2	2
COMPLETED	2	2	1	2	2	3	2	1	2	2
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0
Period Title: Period 1
STARTED	2	2	1	2	2	3	2	1	2	2
COMPLETED	1	2	1	2	2	3	2	1	1	2
NOT COMPLETED	1	0	0	0	0	0	0	0	1	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Participants who were randomized to receive either dofetilide alone, dofetilide + mexiletine, dofetilide + lidocaine, moxifloxacin + diltiazem or placebo.
Overall Participants	22
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.1 (4.9)
Sex: Female, Male (Count of Participants)
Female	9 40.9%
Male	13 59.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 9.1%
Not Hispanic or Latino	20 90.9%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 4.5%
Asian	1 4.5%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	10 45.5%
White	10 45.5%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	22 100%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	69.9 (9.0)
Systolic blood pressure (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	109.5 (5.5)
Diastolic blood pressure (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	60.2 (3.5)
Heart rate (beats per minute (bpm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [beats per minute (bpm)]	61.3 (6.7)
PR interval (ms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ms]	160.8 (19.1)
QRS duration (ms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ms]	86.7 (8.5)
J-Tpeakc (heart rate corrected J-Tpeak interval) (ms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ms]	229.5 (19.0)
Tpeak-Tend interval (ms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ms]	81.9 (6.4)
QTc (Fridericia's heart rate corrected QT interval) (ms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ms]	397.8 (14.2)

Outcome Measures

1. Primary Outcome

Title	Change in Placebo Corrected Change From Baseline QTc and J-Tpeakc Intervals on the ECG Measured in Milliseconds When Dofetilide is Administered With Mexiletine or Lidocaine Compared to When Dofetilide is Administered Alone at Evening Dose on Treatment Day
Description	After 3rd dose of mexiletine or lidocaine (evening dose) on treatment day when combined with dofetilide to evening dose on dofetilide alone day.
Time Frame	5 weeks

Outcome Measure Data

Analysis Population Description

All study participants that completed placebo and dofetilide alone as well as dofetilide + mexiletine and/or dofetilide + lidocaine

Arm/Group Title	Dofetilide Alone	Dofetilide + Mexiletine	Dofetilide + Lidocaine
Arm/Group Description	Subjects that completed placebo and dofetilide alone interventions	Subjects that completed placebo and dofetilide + mexiletine interventions	Subjects that completed placebo and dofetilide + lidocaine interventions
Measure Participants	20	20	18
Placebo corrected change from baseline in QTc	37.9	20.4	18
Placebo corrected change from baseline in J-Tpeakc	24.0	0.8	3.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dofetilide Alone, Dofetilide + Mexiletine
	Comments	Change in QTc interval on the ECG measured in milliseconds when dofetilide is administered with mexiletine compared to when dofetilide is administered alone at evening dose on treatment day.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.025
	Comments	Adjustment for multiple comparisons was performed according to the Bonferroni method.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-19.8
	Confidence Interval	(2-Sided) 95%; -25.2 to -14.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dofetilide Alone, Dofetilide + Lidocaine
	Comments	Change in QTc interval on the ECG measured in milliseconds when dofetilide is administered with lidocaine compared to when dofetilide is administered alone at evening dose on treatment day.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.025
	Comments	Adjustment for multiple comparisons was performed according to the Bonferroni method.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-19.7
	Confidence Interval	(2-Sided) 95%; -25.2 to -14.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Dofetilide Alone, Dofetilide + Mexiletine
	Comments	Change in J-Tpeakc interval on the ECG measured in milliseconds when dofetilide is administered with mexiletine compared to when dofetilide is administered alone at evening dose on treatment day.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.025
	Comments	Adjustment for multiple comparisons was performed according to the Bonferroni method.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-23.2
	Confidence Interval	(2-Sided) 95%; -28.0 to -18.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Dofetilide Alone, Dofetilide + Lidocaine
	Comments	Change in J-Tpeakc interval on the ECG measured in milliseconds when dofetilide is administered with lidocaine compared to when dofetilide is administered alone at evening dose on treatment day.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.025
	Comments	Adjustment for multiple comparisons was performed according to the Bonferroni method.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-20.5
	Confidence Interval	(2-Sided) 95%; -25.5 to -15.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change in Placebo Corrected Change From Baseline QTc Interval on the ECG Measured in Milliseconds When Moxifloxacin is Administered With Diltiazem at the Evening Dose Compared to When Moxifloxacin is Administered Alone at Afternoon Dose on Treatment Day.
Description	Evening dose (moxifloxacin+diltiazem) versus afternoon dose (diltiazem alone).
Time Frame	5 weeks

Outcome Measure Data

Analysis Population Description

All study participants that completed placebo, moxifloxacin and moxifloxacin + diltiazem

Arm/Group Title	Moxifloxacin Alone	Moxifloxacin + Diltiazem
Arm/Group Description	Subjects that completed placebo and moxifloxacin alone interventions	Subjects that completed placebo and moxifloxacin + diltiazem interventions
Measure Participants	19	19
Mean (95% Confidence Interval) [ms]	29.9	31.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dofetilide Alone, Dofetilide + Mexiletine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.025
	Comments	Adjustment for multiple comparisons was performed according to the Bonferroni method.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.9
	Confidence Interval	(2-Sided) 95%; -1 to 6.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Dofetilide		Dofetilide + Lidocaine		Dofetilide + Mexiletine		Moxifloxacin + Diltiazem		Placebo
Arm/Group Description	Dofetilide alone arm Dofetilide: • 8 am: Placebo 12 pm (noon): 250 µg 5:30 pm: 250 µg		Dofetilide combined with lidocaine Dofetilide: • 8 am: Placebo 12 pm (noon): 250 µg 5:30 pm: 250 µg Lidocaine: • 9 am : 30 µg/min per kg (loading) for 60 minutes and 10 µg/min per kg (maintenance) for 30 minutes 2 pm: 55 µg/min per kg (loading) for 60 minutes and 20 µg/min per kg (maintenance) for 30 minutes 7:30 pm: 52 µg/min per kg (loading) for 60 minutes and 20 µg/min per kg (maintenance) for 30 minutes		Dofetilide combined with mexiletine Dofetilide: • 8 am: Placebo 12 pm (noon): 250 µg 5:30 pm: 250 µg Mexiletine: • 8 am: weight x 4 mg/kg 12 pm (noon): Same as at 8 am 5:30 pm: Same as at 8 am		Moxifloxacin with and without diltiazem. Moxifloxacin: • 9 am: 5.63 mg/h per kg (loading) for 1 hour and 0.26 mg/h per kg (maintenance for 30 minutes) 2 pm: 6.14 mg/h per kg (loading) for 1 hour and 0.49 mg/h per kg (maintenance for 30 minutes) 7:30 pm: 2.23 mg/h per kg (loading) for 1 hour and 0.49 mg/h per kg (maintenance for 30 minutes) Diltiazem: • 7:30 pm: 330 µg/h per kg (loading) for 60 minutes and 61 µg/h per kg (maintenance) for 30 minutes		Placebo (#2 gelcap and intravenous saline) Placebo: Placebo (#2 Gelcap or IV saline)
All Cause Mortality
	Dofetilide		Dofetilide + Lidocaine		Dofetilide + Mexiletine		Moxifloxacin + Diltiazem		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Dofetilide		Dofetilide + Lidocaine		Dofetilide + Mexiletine		Moxifloxacin + Diltiazem		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/19 (0%)		0/21 (0%)		0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Dofetilide		Dofetilide + Lidocaine		Dofetilide + Mexiletine		Moxifloxacin + Diltiazem		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/20 (15%)		1/19 (5.3%)		11/21 (52.4%)		6/20 (30%)		3/20 (15%)
Gastrointestinal disorders
Nausea	1/20 (5%)	1	0/19 (0%)	1	4/21 (19%)	4	3/20 (15%)	3	2/20 (10%)	2
Vomiting	1/20 (5%)	1	0/19 (0%)	1	1/21 (4.8%)	1	1/20 (5%)	1	0/20 (0%)	1
Nervous system disorders
Dizzines	1/20 (5%)	1	1/19 (5.3%)	1	6/21 (28.6%)	6	2/20 (10%)	2	1/20 (5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.