Phase I Safety, Pharmacokinetics and Bioavailability Study Comparing Rate and Extent of Absorption of Two Different Forms of Tafamidis (PF-6291826)

Study Overview
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Brief Summary
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2 different formulations and 4 different single doses of tafamidis will be compared. All subjects will receive both formulations and 3 different doses. Subjects will be fasted before taking the drug. After swallowing single dose of tafamidis, tafamidis blood concentrations will be measured periodically for 8 days. After another 16 days, all subjects will repeat the procedure twice, each time with the other formulation/dose.

Official Title
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A PHASE 1, OPEN-LABEL, RANDOMIZED, THREE-PERIOD, THREE-SEQUENCE, SINGLE-DOSE, CROSSOVER STUDY IN FASTED HEALTHY SUBJECTS, TO ASSESS THE SAFETY, PHARMACOKINETICS AND ORAL BIOAVAILABILITY OF TAFAMIDIS FREE ACID WET-MILLED SUSPENSION DOSES, RELATIVE TO 4 X 20 MG COMMERCIAL TAFAMIDIS MEGLUMINE CAPSULES

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Tafamidis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males or females of non-child bearing potential. Body Mass Index (BMI) of 17.5 to 30.5 and total body weight more than 50 kg (110 lbs). Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). Blood pressure at screening visit of greater than 140 mm Hg (systolic) or 90 mg Hg (diastolic). Use of prescription or nonprescription drugs supplements within 7 days prior to the study. Fertile male subjects who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br>4 × 20 mg commercial tafamidis meglumine administered as soft gelatin capsules under fasted conditions | Drug: Tafamidis<br>* bioavailability study<br>|
| Experimental: Treatment B<br>10 mgA tafamidis free acid administered as a wet-milled suspension under fasted conditions | Drug: Tafamidis<br>* bioavailability study<br>|
| Experimental: Treatment C<br>a dose of tafamidis free acid projected to be an equivalent of 4 × 20 mg commercial tafamidis meglumine administered as a wet-milled suspension under fasted conditions | Drug: Tafamidis<br>* bioavailability study<br>|
| Experimental: Treatment D<br>a dose of tafamidis free acid projected to be an equivalent of 5 × 20 mg commercial tafamidis meglumine administered as a wet-milled suspension under fasted conditions | Drug: Tafamidis<br>* bioavailability study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Area under the plasma concentration-time profile from time 0 extrapolated to infinite time (AUCinf) |  | 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hrs | 
| 2. Maximum Observed Plasma Concentration (Cmax) |  | 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hrs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Area under the plasma concentration-time profile from time 0 to 24 hours post-dose (AUC24) |  | 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hrs | 
| 2. Area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration (AUClast) |  | 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hrs | 
| 3. Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hrs |