Clinical trial NCT01359618: Determining Highest Dose Administration of TC-5214 and Evaluating Effect on the Electrical Activity in the Heart
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy Male
Keywords: Phase I
Safety
tolerability
healthy
major depressive disorder
thorough QT
maximum tolerated dose
elimination
heart electrical signal
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2011-05-25
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Up to 24 hours
measure: 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.
timeFrame: Up to 24 hours
measure: 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.
timeFrame: Up to 24 hours
measure: 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).
timeFrame: Up to 24 hours
measure: 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.
timeFrame: Up to 24 hours
measure: 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).
timeFrame: Up to 24 hours
Secondary outcomes:
measure: 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
timeFrame: Up to 72 Hours
measure: Part B: A change in the maximum of the mean change in time-matched ECG interval, measured from the onset of the QRS complex
timeFrame: Up to 24 Hours
measure: Part B: Assay sensitivity by measuring the effect of moxifloxacin 400 mg on QTc compared to placebo
timeFrame: Up to 24 hours
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Hans A Eriksson, MD, PhD, MBA
role: STUDY_DIRECTOR
affiliation: Quintiles Drug Research Unit at Guy's Hospital
name: Darren Wilbraham, MBBS DCPSA
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca
name: Brendan Smyth, MD
role: STUDY_CHAIR
References: