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

NCT01359618 | Terminated Phase 1

• 1 other identifier: D4130C00009
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Male

Keywords

Phase I; Safety; tolerability; healthy; major depressive disorder; thorough QT; maximum tolerated dose; elimination; heart electrical signal

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (3)

• 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

Study Arms (6)

Part A 1

EXPERIMENTAL

TC-5214

Drug: TC-5214

Part A 2

EXPERIMENTAL

TC-5214 placebo

Other: Placebo comparator

Part B 1

EXPERIMENTAL

TC-5214 8 mg + moxifloxacin placebo

Drug: TC-5214; Other: Moxifloxacin placebo comparator

Part B 2

EXPERIMENTAL

TC-5214 supratherapeutic dose + moxifloxacin placebo

Drug: TC-5214; Other: Moxifloxacin placebo comparator

Part B 3

ACTIVE COMPARATOR

TC-5214 placebo + moxifloxacin 400 mg

Other: Placebo comparator; Drug: Moxifloxacin

Part B 4

PLACEBO COMPARATOR

TC-5214 placebo + moxifloxacin placebo

Other: Placebo comparator; Other: Moxifloxacin placebo comparator

Interventions

TC-5214 DRUG

Single dose, oral tablets

Part A 1; Part B 1; Part B 2

Placebo comparator OTHER

Single dose, oral tablets

Part A 2; Part B 3; Part B 4

Moxifloxacin DRUG

Single dose, oral encapsulated tablet

Also known as: Avelox®

Part B 3

Moxifloxacin placebo comparator OTHER

Single dose, oral encapsulated tablet

Part B 1; Part B 2; Part B 4

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

London, United Kingdom

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Moxifloxacin

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Hans A Eriksson, MD, PhD, MBA

  AstraZeneca

  STUDY DIRECTOR

• Darren Wilbraham, MBBS DCPSA

  Quintiles Drug Research Unit at Guy's Hospital

  PRINCIPAL INVESTIGATOR

• Brendan Smyth, MD

  AstraZeneca

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2011
• First Posted: May 25, 2011
• Study Start: June 1, 2011
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: December 12, 2012

Record last verified: 2012-12

Locations

GB (1)