Guanfacine Immediate-release Electrocardiogram Results (QTc) Study

Study Overview
=================
Brief Summary
-----------------
To assess the effect of immediate-release guanfacine hydrochloride, administered at therapeutic and supratherapeutic doses, on QT/QTc in healthy normal males and females

Official Title
-----------------
A Phase I, Randomized, Gender Stratified, Double-Blind, Placebo- and Positive-Controlled, Three Period Crossover Trial to Assess the Effect of Guanfacine Hydrochloride on QT/QTc Interval in Healthy Men and Women

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Drug: immediate release guanfacine hydrochloride
* Drug: moxifloxacin
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy Normal Subjects

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immediate-release Guanfacine HCl<br> | Drug: immediate release guanfacine hydrochloride<br>* Subjects will receive 2x2mg immediate-release guanfacine on day 1. Subjects will receive 4x2mg immediate-release guanfacine on day 6.<br>* Other names: Tenex;|
| Active Comparator: Moxifloxacin HCl<br> | Drug: moxifloxacin<br>* Subjects will receive 400mg of moxifloxacin on day 1. Subjects will receive 400mg of moxifloxacin on day 6.<br>* Other names: Avelox;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Subjects will receive placebo on Day 1. Subjects will receive placebo on Day 6.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Electrocardiogram Results (QTcNi) at Time of Maximum Plasma Concentration (Tmax) on Day 1 | QTcNi is the QT interval using a subject-specific correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation. | Baseline, Tmax (time of subject-specific maximum plasma concentration) | 
| Change From Baseline in Electrocardiogram Results (QTcNi) at Tmax on Day 6 | QTcNi is the QT interval using a subject-specific correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation. | Baseline and Tmax (time of subject-specific maximum plasma concentration) | 
| Change From Baseline in Electrocardiogram Results (QTcF) at Tmax on Day 1 | QTcF is the QT interval using Fridericia's correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation. | Baseline and Tmax (time of subject-specific maximum plasma concentration) | 
| Change From Baseline in Electrocardiogram Results (QTcF) at Tmax on Day 6 | QTcF is the QT interval using Fridericia's correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation. | Baseline and Tmax (time of subject-specific maximum plasma concentration) | 
| Change From Baseline in Heart Rate (HR) at Tmax on Day 1 |  | Baseline and Tmax (time of subject-specific maximum plasma concentration) | 
| Change From Baseline in Heart Rate (HR) at Tmax on Day 6 |  | Baseline and Tmax (time of subject-specific maximum plasma concentration) | 
| Change From Baseline in Electrocardiogram Results (QT) Interval at Tmax on Day 1 | QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). | Baseline and Tmax (time of subject-specific maximum plasma concentration) | 
| Change From Baseline in Electrocardiogram Results (QT) Interval at Tmax on Day 6 | QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). | Baseline and Tmax (time of subject-specific maximum plasma concentration) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) of Guanfacine and Moxifloxacin on Day 1 |  | pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose | 
| Maximum Plasma Concentration (Cmax) of Guanfacine and Moxifloxacin on Day 6 |  | pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose | 
| Time of Maximum Plasma Concentration (Tmax) of Guanfacine and Moxifloxacin on Day 1 |  | pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose | 
| Time of Maximum Plasma Concentration (Tmax) of Guanfacine and Moxifloxacin on Day 6 |  | pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose | 
| Area Under the Steady-state Plasma Concentration-time Curve (AUC) for Guanfacine and Moxifloxacin on Day 1 |  | pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose | 
| Area Under the Steady-state Plasma Concentration-time Curve (AUC) for Guanfacine and Moxifloxacin on Day 6 |  | pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
QT/QTc