Clinical trial NCT01873950
Conditions: Drug-induced Surface ECG Changes
Sponsor: Food and Drug Administration (FDA)
Start date: 2013-05-01; Completion date: 2014-12-01
Enrollment: 22 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
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.

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:

1. 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.
2. 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.
3. 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).
4. 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.
5. 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.
6. Subject is highly likely (as determined by the investigator) to comply with the protocol-defined procedures and to complete the study.

Arms: arm 1: Ranolazine arm 2: Dofetilide arm 3: Verapamil arm 4: Quinidine sulfate arm 5: Placebo
Interventions: intervention 1: Ranolazine intervention 2: Dofetilide intervention 3: Verapamil intervention 4: Quinidine sulfate intervention 5: Placebo
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: None

Protocol documents: