Determining Highest Dose Administration of TC-5214 and Evaluating Effect on the Electrical Activity in the Heart
Phase 1
Terminated
- Conditions
- Healthy Male
- Interventions
- Registration Number
- NCT01359618
- Lead Sponsor
- AstraZeneca
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Male
- Target Recruitment
- 16
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Part A 2 Placebo comparator TC-5214 placebo Part B 1 TC-5214 TC-5214 8 mg + moxifloxacin placebo Part B 1 Moxifloxacin placebo comparator TC-5214 8 mg + moxifloxacin placebo Part B 2 TC-5214 TC-5214 supratherapeutic dose + moxifloxacin placebo Part A 1 TC-5214 TC-5214 Part B 2 Moxifloxacin placebo comparator TC-5214 supratherapeutic dose + moxifloxacin placebo Part B 3 Placebo comparator TC-5214 placebo + moxifloxacin 400 mg Part B 4 Placebo comparator TC-5214 placebo + moxifloxacin placebo Part B 4 Moxifloxacin placebo comparator TC-5214 placebo + moxifloxacin placebo Part B 3 Moxifloxacin TC-5214 placebo + moxifloxacin 400 mg
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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
Trial Locations
- Locations (1)
Research Site
🇬🇧London, United Kingdom