A Study Comparing Two Forms of Tafamidis Without Food and the Amount of Tafamidis in the Blood With Food

A PHASE 1, OPEN-LABEL, RANDOMIZED, CROSSOVER, SINGLE DOSE STUDY TO DETERMINE THE BIOEQUIVALENCE OF 12.2 MG TAFAMIDIS FREE ACID TABLETS AND COMMERCIAL 20 MG TAFAMIDIS MEGLUMINE CAPSULES ADMINISTERED UNDER FASTED CONDITIONS AND THE EFFECT OF FOOD ON ORAL BIOAVAILABILITY OF 12.2 MG TAFAMIDIS FREE ACID TABLETS IN HEALTHY ADULT PARTICIPANTS

The purpose of this clinical trial is to compare a tablet and a capsule form of tafamidis without food and to assess the amount of tafamidis in blood after taking the tablet form with food.

This study is seeking healthy participants over the age of 18.

All participants in the study will receive either one tablet or capsule of study medicine on the first day without food, then receive one dose of the other tablet or capsule form 16 days later without food. All participants will then receive one dose of the tablet form with food 16 days later.

We will evaluate the amounts in blood for 8 days after taking each dose of the study medicine.

Participants will take part in this study for about 96 days. The first visit is a screening visit to ensure that participants are appropriate for the study. Up to 28 days later, eligible participants will visit the study clinic three times (and stay overnight in the clinical research center for 8 nights each time). The study team will also call participants over the phone 28 to 35 days after the last dose of medicine.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Tafamidis free acid tablet (Test); Drug: Tafamidis meglumine capsule (Reference)

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M1S 3V6
      • Pharma Medica Research Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

1. Participants aged 18 years or older (or the minimum age of consent in accordance with local regulations) at screening.
2. Healthy female participants of nonchildbearing potential and/or male participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, and laboratory tests.
3. BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).

Exclusion Criteria:

Medical Conditions:

1. 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).

   • Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
   • History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, HBcAb, or HCVAb. Hepatitis B vaccination is allowed.
   • Hypersensitivity to any component of the formulations

2. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions or situations related to COVID-19 pandemic (eg, Contact with positive case, residence, or travel to an area with high incidence) that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.

   Prior/Concomitant Therapy:

3. Use of prescription or nonprescription drugs, dietary and herbal supplements within 7 days or 5 half lives (whichever is longer) prior to the first dose of study intervention. (Refer to Section 6.9 Prior and Concomitant Therapy for additional details).

4. Current use of any prohibited concomitant medication(s) or participant unwilling/unable to use a permitted concomitant medication(s). Refer to Section 6.9 Prior and Concomitant Therapy.

   Prior/Concurrent Clinical Study Experience:

5. Previous administration with an investigational product (drug or vaccine) within 6 months (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).

   Diagnostic Assessments:

6. A positive urine drug test.
7. Screening seated BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of seated rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility.
8. Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, QTcF >450 ms, complete LBBB, signs of an acute or indeterminate age myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, second or third degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If the uncorrected QT interval is >450 ms, this interval should be rate-corrected using the Fridericia method only and the resulting QTcF should be used for decision making and reporting. If QTcF exceeds 450 ms, or QRS exceeds 120 ms, the ECG should be repeated twice and the average of the 3 QTcF or QRS values used to determine the participant's eligibility. Computer-interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding a participant.

9. Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary:

   • AST or ALT level ≥ 1.5 × ULN;
   • Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN.

   Other Exclusion Criteria:

10. History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 1 ounce (30 mL) of 40% spirit, or 3 ounces (90 mL) of wine).
11. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
12. History of sensitivity to heparin or heparin induced thrombocytopenia.
13. Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.
14. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
15. Use of tobacco or nicotine-containing products in excess of the equivalent of 5 cigarettes per day.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test tablet (fasted) followed by Reference capsule (fasted) followed by Test tablet (fed); On Day 1 of each period, participants will receive a single dose of one of the tafamidis formulations under fasted or fed conditions. Each period is separated by a washout of at least 16 days between administration of study drug.	Drug: Tafamidis free acid tablet (Test); 12.2 mg tafamidis free acid tablet (Test); Drug: Tafamidis meglumine capsule (Reference); Commercial 20 mg tafamidis meglumine capsule (Reference)
Experimental: Reference capsule (fasted) followed by Test tablet (fasted) followed by Test tablet (fed); On Day 1 of each period, participants will receive a single dose of one of the tafamidis formulations under fasted or fed conditions. Each period is separated by a washout of at least 16 days between administration of study drug.	Drug: Tafamidis free acid tablet (Test); 12.2 mg tafamidis free acid tablet (Test); Drug: Tafamidis meglumine capsule (Reference); Commercial 20 mg tafamidis meglumine capsule (Reference)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics(PK) Parameter - Area Under the Concentration-time Curve to Infinity (AUCinf) of PF-06291826	AUCinf is defined as area under the concentration-time curve from time 0 to infinity, and calculated by AUC(0-tlast) + (Clast*/kel), where Clast* is the estimated plasma concentration at the last quantifiable time point (Clast) estimated form the log-linear regression analysis Clast* = Clast x e^(-kel x tlast)	Predose and 0.5, 1,2,3,4,6,8,12,24 (Day 2),48 (Day 3),72 (Day 4),96 (Day 5),120 (Day 6),144 (Day 7), and 168 (Day 8) hours post dose
PK Parameter - Maximum Observed Concentration (Cmax) of PF-06291826	Cmax is defined as maximum observed concentration.	Predose and 0.5, 1,2,3,4,6,8,12,24 (Day 2),48 (Day 3),72 (Day 4),96 (Day 5),120 (Day 6),144 (Day 7), and 168 (Day 8) hours post dose

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2022
• Primary Completion (Actual): December 18, 2022
• Study Completion (Actual): December 19, 2022

Study Registration Dates

• First Submitted: August 10, 2022
• First Submitted That Met QC Criteria: August 10, 2022
• First Posted (Actual): August 12, 2022

Study Record Updates

• Last Update Posted (Actual): June 3, 2024
• Last Update Submitted That Met QC Criteria: May 31, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Tafamidis, B3461103
• Other Study ID Numbers: B3461103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No