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

Healthy Male Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01359618
• Other study ID #: D4130C00009
• Status: Terminated
• Phase: Phase 1
• First received: April 28, 2011
• Last updated: December 11, 2012
• Start date: June 2011
• Est. completion date: April 2012

Study information

• Verified date: December 2012
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy Male

Intervention

Drug:
• TC-5214
Single dose, oral tablets

Other:
• Placebo comparator
Single dose, oral tablets

Drug:
• Moxifloxacin
Single dose, oral encapsulated tablet

Other:
• Moxifloxacin placebo comparator
Single dose, oral encapsulated tablet

Locations

Country	Name	City	State
United Kingdom	Research Site	London

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	Part B: Assay sensitivity by measuring the effect of moxifloxacin 400 mg on QTc compared to placebo		Up to 24 hours	No