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

December 11, 2012 updated by: AstraZeneca

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.

Study Overview

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A 1
TC-5214
Single dose, oral tablets
Experimental: Part A 2
TC-5214 placebo
Single dose, oral tablets
Experimental: Part B 1
TC-5214 8 mg + moxifloxacin placebo
Single dose, oral tablets
Single dose, oral encapsulated tablet
Experimental: Part B 2
TC-5214 supratherapeutic dose + moxifloxacin placebo
Single dose, oral tablets
Single dose, oral encapsulated tablet
Active Comparator: Part B 3
TC-5214 placebo + moxifloxacin 400 mg
Single dose, oral encapsulated tablet
Other Names:
  • Avelox®
Single dose, oral tablets
Placebo Comparator: Part B 4
TC-5214 placebo + moxifloxacin placebo
Single dose, oral tablets
Single dose, oral encapsulated tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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
Time Frame: Up to 24 hours
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.
Time Frame: Up to 24 hours
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.
Time Frame: Up to 24 hours
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).
Time Frame: Up to 24 hours
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.
Time Frame: Up to 24 hours
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).
Time Frame: Up to 24 hours
Up to 24 hours

Secondary Outcome Measures

Outcome Measure
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
Time Frame: Up to 72 Hours
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
Time Frame: Up to 24 Hours
Up to 24 Hours
Part B: Assay sensitivity by measuring the effect of moxifloxacin 400 mg on QTc compared to placebo
Time Frame: Up to 24 hours
Up to 24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Director: Hans A Eriksson, MD, PhD, MBA, AstraZeneca
  • Study Chair: Brendan Smyth, MD, AstraZeneca

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2011

Primary Completion (Actual)

April 1, 2012

Study Completion (Actual)

April 1, 2012

Study Registration Dates

First Submitted

April 28, 2011

First Submitted That Met QC Criteria

May 23, 2011

First Posted (Estimate)

May 25, 2011

Study Record Updates

Last Update Posted (Estimate)

December 12, 2012

Last Update Submitted That Met QC Criteria

December 11, 2012

Last Verified

December 1, 2012

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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