Study of the Electrocardiographic Effects of Ranolazine, Dofetilide, Verapamil, and Quinidine in Healthy Subjects
Condition: Drug-induced Surface ECG Changes
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Ranolazine; Dofetilide; Verapamil; Quinidine sulfate; Placebo
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention MeSH terms: Quinidine; Quinidine gluconate; Verapamil; Dofetilide; Ranolazine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment