Determining Highest Dose Administration of TC-5214 and Evaluating Effect on the Electrical Activity in the Heart

A Single-centre, Randomised, Double-blind, Placebo Controlled Phase I Study in Two Parts: Part A to Assess a Safe and Tolerable Supratherapeutic Dose of TC-5214 After Single Ascending Oral Doses in Healthy Male Subjects, Followed by Part B: A Four-period Double-dummy Crossover Study to Investigate the Effect of 2 Single Doses (Therapeutic and Supratherapeutic) of TC-5214 on the QT/QTc Interval, Compared to Placebo, Using Moxifloxacin (Avelox®) as a Positive Control, in Healthy Male Subjects

This is a two part study. Part A will determine the maximum tolerated dose of TC-5214 administered to healthy male subjects in single ascending oral doses. This part of the study will define the highest dose of TC-5214 to be administered in Part B. Part B of this study will investigate the effect of TC-5214 on the electrical activity of the heart following single oral administration. The study will be carried out healthy male subjects in a four period crossover study with TC-5214 compared to placebo and oral moxifloxacin as a positive control. The safety, tolerability and pharmacokinetics of TC-5214 will also be evaluated.

Inclusion Criteria:

• Healthy male 18 to 50 years old inclusive with suitable veins for cannulation or repeated venipuncture
• Have a body mass index (BMI) between 19 and 30 kg/m2 inclusive and weigh at least 50 kg
• Male subjects should be willing to use a double barrier method of contraception (condom with spermicide) from the first dose of investigational product until 3 months after the last dose of investigational product
• Be able to understand and comply with the requirements of the study as judged by the investigator

Exclusion Criteria:

• History of any clinically significant medical, neurologic or psychiatric disease or disorder which, in the opinion of the Investigator and Sponsor may either put the subject at risk because of participation in the study, or influence the results of the subject's ability to participate in the study
• History or presence of gastrointestinal (including irritable bowel disease), hepatic, or renal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of study drug. Subjects with a history of surgery on the gastrointestinal tract (not including appendectomy or cholecystectomy) should also be excluded
• History of seizure activity, including febrile seizures
• Prolonged QTcF >450 ms or shortened QTcF <340 ms, or family history of Long QT Syndrome
• Use of concomitant medications that prolong QT/QTc interval