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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Male

Intervention / Treatment
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* Drug: TC-5214
* Other: Placebo comparator
* Drug: Moxifloxacin
* Other: Moxifloxacin placebo comparator


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A 1<br>TC-5214 | Drug: TC-5214<br>* Single dose, oral tablets<br>|
| Experimental: Part A 2<br>TC-5214 placebo | Other: Placebo comparator<br>* Single dose, oral tablets<br>|
| Experimental: Part B 1<br>TC-5214 8 mg + moxifloxacin placebo | Drug: TC-5214<br>* Single dose, oral tablets<br>Other: Moxifloxacin placebo comparator<br>* Single dose, oral encapsulated tablet<br>|
| Experimental: Part B 2<br>TC-5214 supratherapeutic dose + moxifloxacin placebo | Drug: TC-5214<br>* Single dose, oral tablets<br>Other: Moxifloxacin placebo comparator<br>* Single dose, oral encapsulated tablet<br>|
| Active Comparator: Part B 3<br>TC-5214 placebo + moxifloxacin 400 mg | Other: Placebo comparator<br>* Single dose, oral tablets<br>Drug: Moxifloxacin<br>* Single dose, oral encapsulated tablet<br>* Other names: Avelox®;|
| Placebo Comparator: Part B 4<br>TC-5214 placebo + moxifloxacin placebo | Other: Placebo comparator<br>* Single dose, oral tablets<br>Other: Moxifloxacin placebo comparator<br>* Single dose, oral encapsulated tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: To examine the safety and tolerability of TC-5214. The following assessments will be measured and reported: The number of participants with adverse events |  | Up to 24 hours | 
| Part A: To examine the safety and tolerability of TC-5214. The following assessments will be measured and reported: A change from baseline in laboratory assessments. |  | Up to 24 hours | 
| Part A: To examine the safety and tolerability of TC-5214. The following assessments will be measured and reported: A change from baseline in vital signs. |  | Up to 24 hours | 
| Part A: To examine the safety and tolerability of TC-5214. The following assessments will be measured and reported: A change from baseline in electrocardiogram (ECG). |  | Up to 24 hours | 
| Part A: To examine the safety and tolerability of TC-5214. The following assessments will be measured and reported: A change from baseline in physical examination. |  | Up to 24 hours | 
| Part B: The maximum mean change in time-matched ECG interval, measured from the onset of the QRS complex to the T point, using the best heart rate correction method (QTc). |  | Up to 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: TC-5214 Plasma and urine pharmacokinetic variable to be measured: including, C max, time to C max, Area Under Curve (AUC) (0-t), terminal half life, cumulative amount of drug excreted unchanged into urine from zero to time and renal clearance |  | Up to 72 Hours | 
| Part B: A change in the maximum of the mean change in time-matched ECG interval, measured from the onset of the QRS complex |  | Up to 24 Hours | 
| Part B: Assay sensitivity by measuring the effect of moxifloxacin 400 mg on QTc compared to placebo |  | Up to 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, Safety, tolerability, healthy, major depressive disorder, thorough QT, maximum tolerated dose, elimination, heart electrical signal