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

Purpose

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.

Condition	Intervention	Phase
Healthy Male	Drug: TC-5214 Other: Placebo comparator Drug: Moxifloxacin Other: Moxifloxacin placebo comparator	Phase 1

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

Resource links provided by NLM:

Drug Information available for: Moxifloxacin Moxifloxacin hydrochloride

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Part B: Assay sensitivity by measuring the effect of moxifloxacin 400 mg on QTc compared to placebo [ Time Frame: Up to 24 hours ] [ Designated as safety issue: No ]

Enrollment:	16
Study Start Date:	June 2011
Study Completion Date:	April 2012
Primary Completion Date:	April 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Part A 1 TC-5214	Drug: TC-5214 Single dose, oral tablets
Experimental: Part A 2 TC-5214 placebo	Other: Placebo comparator Single dose, oral tablets
Experimental: Part B 1 TC-5214 8 mg + moxifloxacin placebo	Drug: TC-5214 Single dose, oral tablets Other: Moxifloxacin placebo comparator Single dose, oral encapsulated tablet
Experimental: Part B 2 TC-5214 supratherapeutic dose + moxifloxacin placebo	Drug: TC-5214 Single dose, oral tablets Other: Moxifloxacin placebo comparator Single dose, oral encapsulated tablet
Active Comparator: Part B 3 TC-5214 placebo + moxifloxacin 400 mg	Other: Placebo comparator Single dose, oral tablets Drug: Moxifloxacin Single dose, oral encapsulated tablet Other Name: Avelox®
Placebo Comparator: Part B 4 TC-5214 placebo + moxifloxacin placebo	Other: Placebo comparator Single dose, oral tablets Other: Moxifloxacin placebo comparator Single dose, oral encapsulated tablet

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01359618

Locations

United Kingdom
Research Site
London, United Kingdom

Sponsors and Collaborators

AstraZeneca

Investigators

Study Director:	Hans A Eriksson, MD, PhD, MBA	AstraZeneca
Principal Investigator:	Darren Wilbraham, MBBS DCPSA	Quintiles Drug Research Unit at Guy's Hospital
Study Chair:	Brendan Smyth, MD	AstraZeneca

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01359618 History of Changes
Other Study ID Numbers:	D4130C00009
Study First Received:	April 28, 2011
Last Updated:	December 11, 2012
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:

Phase I
Safety
tolerability
healthy
major depressive disorder

thorough QT
maximum tolerated dose
elimination
heart electrical signal

Additional relevant MeSH terms:

Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Contraceptives, Oral, Combined

Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 22, 2013