A Study To Determine Any Effect Of Tafamidis On Electrocardiographic Intervals, Specifically The Rate Corrected QT Interval (QTc)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate the effects of tafamidis on the intervals of the electrocardiogram, specifically the rate corrected QT interval (QTc) in healthy volunteers.

Official Title
-----------------
A Randomized, Placebo- And Positive-Controlled Cross-Over Study To Evaluate The Effect Of Tafamidis On The QTC Interval In Healthy Volunteers

Conditions
-----------------
TTR Cardiomyopathy

Intervention / Treatment
-----------------
* Drug: Period 1
* Drug: Period 2
* Drug: Period 3


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy, nonsmoking, male and/or female subjects of non-childbearing potential. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2. Total body weight >50 kg (110 lbs). Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease. An ALT or AST measurement >2 times the ULN. 12-lead ECG demonstrating QTc >450 msec or a QRS interval >120 msec at Screening. Subjects at increased risk if dosed with moxifloxacin, according to the product label for moxifloxacin. History of risk factors of QT prolongation or torsades de pointes, congenital deafness and family history of sudden death.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Period 1: 960 mg tafamidis (Vyndaqel)<br> | Drug: Period 1<br>* A comparison of less than or equal to 960 mg tafamidis, 400 mg moxifloxacin and placebo on the rate corrected QT interval.<br>* Other names: tafamidis (Vyndaqel);|
| Experimental: Period 2: 400 mg moxifloxacin<br>400 mg moxifloxacin | Drug: Period 2<br>* A comparison of less than or equal to 960 mg tafamidis, 400 mg moxifloxacin and placebo on the rate corrected QT interval.<br>* Other names: moxifloxacin;|
| Experimental: Period 3: Placebo<br> | Drug: Period 3<br>* A comparison of less than or equal to 960 mg tafamidis, 400 mg moxifloxacin and placebo on the rate corrected QT interval.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| QTc interval using Fridericia's correction method (QTcF) of tafamidis and placebo (baseline-adjusted) at each post-dose time |  | SCRN, -1, -0.5, 0, 1, 1.5, 2, 3, 4, 6, 12, 24 hrs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| QTcF of moxifloxacin and placebo at historical moxifloxacin median Tmax of 3 hours. |  | Scrn, -1, -0.5, 0, 1, .5, 2, 3, 4, 6, 8, 12, 24 hrs | 
| Tmax |  | 0, 1, .5, 2, 3, 4, 6, 8, 12, 24 hrs | 
| Cmax |  | 0, 1, .5, 2, 3, 4, 6, 8, 12, 24 hrs | 
| AUC0-24 |  | 0, 1, .5, 2, 3, 4, 6, 8, 12, 24 hrs | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Thorough QTc evaluation of tafamidis compared to the effects of moxifloxacin and placebo in healthy volunteers.