A Study to Learn How Different Forms of Study Medicine Tafamidis Are Taken Up Into The Blood in Healthy Adults

A PHASE 1, OPEN-LABEL, RANDOMIZED, THREE-TREATMENT, THREE-PERIOD, CROSSOVER, SINGLE DOSE STUDY TO ESTIMATE THE RELATIVE BIOAVAILABILITY OF 61 MG AND 70 MG TAFAMIDIS FREE ACID TABLETS TO COMMERCIAL 61 MG TAFAMIDIS FREE ACID CAPSULE ADMINISTERED UNDER FASTED CONDITIONS IN HEALTHY ADULT PARTICIPANTS

The purpose of this clinical trial is to compare the amount of tafamidis in the blood of healthy adult participants after taking three different forms of tafamidis by mouth.

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy
• Intervention / Treatment: Drug: Tafamidis 61 mg free acid tablet (Test 1); Drug: Tafamidis 70 mg free acid tablet (Test 1); Drug: Tafamidis 61 mg free acid capsule (Reference)

Detailed Description

A new tafamidis free acid tablet is being developed to be bioequivalent to the current commercial 61 mg tafamidis free acid capsule. The purpose of the study is to estimate the relative bioavailability of 61 mg tafamidis free acid tablet (Test 1) and 70 mg tafamidis free acid tablet (Test 2) to 61 mg tafamidis free acid capsule (Reference, the clinical supply form of the current commercial 61 mg tafamidis free acid capsule) administered under fasted conditions in healthy adult participants.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

Study Locations

• Belgium
  • Bruxelles-capitale, Région DE
    • Brussels, Bruxelles-capitale, Région DE, Belgium, B-1070
      • Pfizer Clinical Research Unit - Brussels

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Age and Sex:

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.

   Other Inclusion Criteria:

3. BMI of 16-32 kg/m2; and a total body weight >45 kg (99 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. Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions 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 and dietary and herbal supplements within 7 days or 5 half lives (whichever is longer) prior to the first dose of study intervention.

4. Current use of any prohibited concomitant medication(s) or participant unwilling or unable to use a required concomitant medication(s).

   Prior/Concurrent Clinical Study Experience:

5. Previous administration of an investigational product (drug or vaccine) within 30 days (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. A single repeat for positive drug screen may be allowed.
7. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic) for participants <60 years; and ≥150/90 mm/Hg for participants ≥60 years old, following at least 5 minutes of supine rest. If systolic BP is ≥140 or 150 mm Hg (based on age) or diastolic ≥90 mm Hg, 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 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. Renal impairment as defined by an eGFR of <60 mL/min/1.73 m².

10. 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:

    • ALT, AST, Bilirubin ≥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:

11. 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).
12. Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.
13. 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.

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

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test 1 tablet followed by Test 2 tablet followed by Reference capsule; On Day 1 of each period, participants will receive a single dose of 1 of the tafamidis formulations. Each period is separated by a washout of at least 16 days between administration of study drug	Drug: Tafamidis 61 mg free acid tablet (Test 1); Tafamidis 61 mg free acid tablet (Test 1); Drug: Tafamidis 70 mg free acid tablet (Test 1); Tafamidis 61 mg free acid tablet (Test 1); Drug: Tafamidis 61 mg free acid capsule (Reference); Tafamidis 61 mg free acid capsule (Reference)
Experimental: Test 1 tablet followed by Reference capsule followed by Test 2 tablet; On Day 1 of each period, participants will receive a single dose of 1 of the tafamidis formulations. Each period is separated by a washout of at least 16 days between administration of study drug	Drug: Tafamidis 61 mg free acid tablet (Test 1); Tafamidis 61 mg free acid tablet (Test 1); Drug: Tafamidis 70 mg free acid tablet (Test 1); Tafamidis 61 mg free acid tablet (Test 1); Drug: Tafamidis 61 mg free acid capsule (Reference); Tafamidis 61 mg free acid capsule (Reference)
Experimental: Test 2 tablet followed by Reference capsule followed by Test 1 tablet; On Day 1 of each period, participants will receive a single dose of 1 of the tafamidis formulations. Each period is separated by a washout of at least 16 days between administration of study drug	Drug: Tafamidis 61 mg free acid tablet (Test 1); Tafamidis 61 mg free acid tablet (Test 1); Drug: Tafamidis 70 mg free acid tablet (Test 1); Tafamidis 61 mg free acid tablet (Test 1); Drug: Tafamidis 61 mg free acid capsule (Reference); Tafamidis 61 mg free acid capsule (Reference)
Experimental: Test 2 tablet followed by Test 1 tablet followed by Reference capsule; On Day 1 of each period, participants will receive a single dose of 1 of the tafamidis formulations. Each period is separated by a washout of at least 16 days between administration of study drug	Drug: Tafamidis 61 mg free acid tablet (Test 1); Tafamidis 61 mg free acid tablet (Test 1); Drug: Tafamidis 70 mg free acid tablet (Test 1); Tafamidis 61 mg free acid tablet (Test 1); Drug: Tafamidis 61 mg free acid capsule (Reference); Tafamidis 61 mg free acid capsule (Reference)
Experimental: Reference capsule followed by Test 1 tablet followed by Test 2 tablet; On Day 1 of each period, participants will receive a single dose of 1 of the tafamidis formulations. Each period is separated by a washout of at least 16 days between administration of study drug	Drug: Tafamidis 61 mg free acid tablet (Test 1); Tafamidis 61 mg free acid tablet (Test 1); Drug: Tafamidis 70 mg free acid tablet (Test 1); Tafamidis 61 mg free acid tablet (Test 1); Drug: Tafamidis 61 mg free acid capsule (Reference); Tafamidis 61 mg free acid capsule (Reference)
Experimental: Reference capsule followed by Test 2 tablet followed by Test 1 tablet; On Day 1 of each period, participants will receive a single dose of 1 of the tafamidis formulations. Each period is separated by a washout of at least 16 days between administration of study drug	Drug: Tafamidis 61 mg free acid tablet (Test 1); Tafamidis 61 mg free acid tablet (Test 1); Drug: Tafamidis 70 mg free acid tablet (Test 1); Tafamidis 61 mg free acid tablet (Test 1); Drug: Tafamidis 61 mg free acid capsule (Reference); Tafamidis 61 mg free acid capsule (Reference)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the concentration-time curve (AUCinf)	Area under the plasma concentration time profile from time zero extrapolated to infinite time	Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168
Maximum observed plasma concentration (Cmax)	Peak or maximum observed concentration	Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168

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): February 27, 2024
• Primary Completion (Estimated): May 27, 2024
• Study Completion (Estimated): May 27, 2024

Study Registration Dates

• First Submitted: February 15, 2024
• First Submitted That Met QC Criteria: February 15, 2024
• First Posted (Actual): February 23, 2024

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: tafamidis
• Other Study ID Numbers: B3461114

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