Safety And Pharmacokinetic Assessment Of Orally Administered Tafamidis In Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
This study in healthy male and female volunteers will investigate the safety and tolerability of three increasing oral doses of tafamidis

Official Title
-----------------
A Phase 1, Randomized, Double-Blind, Crossover, Ascending Dose-Tolerance Study To Assess The Safety And Pharmacokinetics Of Tafamidis Doses Greater Than 120 Mg As Oral Solution In Healthy Volunteers

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

Intervention / Treatment
-----------------
* Drug: Tafamidis
* Drug: Tafamidis
* Drug: Tafamidis


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy, males or females, 21 to 55 years old. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2. Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). Condition affecting drug absorption. Blood pressure or ECG abnormalities. Recent treatment with an investigational, prescription, or non-prescription drug

Ages Eligible for Study
-----------------
Minimum Age: 21 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Period 1<br>240 mg tafamidis arm | Drug: Tafamidis<br>* 240 mg, solution, single dose<br>|
| Experimental: Period 2<br>480 mg arm | Drug: Tafamidis<br>* 480 mg, solution, single dose<br>|
| Experimental: Period 3<br>TBD dose | Drug: Tafamidis<br>* TBD dose will be a single dose if < 720 mg or a loading dose followed by additional dose if > 720 mg.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety and tolerability of orally administered tafamidis in healthy volunteers at escalating doses >120 mg. Safety assessments will include spontaneous reporting of adverse events, concomitant medications, physical examination, |  | Day 0 and Day 6 | 
| vital signs, ECGs, and clinical laboratory tests. |  | Day 0 and Day 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax - Maximum Observed Plasma Concentration (Cmax) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hrs | 
| tmax - Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hrs | 
| AUC0-24 - AreArea under the Concentration-Time Curve (AUC) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hrs | 
| AUClast - Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hrs | 
| AUCinf - Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hrs | 
| t½ - Plasma Decay Half-Life (t1/2) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hrs | 
| Transthyretin blood concentration in mg/dL |  | Days 0,1,2,3,4,5,6 | 
| Transthyretin stabilization (%) |  | Days 0,1,2,3,4,5,6 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pharmacokinetic, pharmacodynamic