A Study to Determine the Bioequivalence of Two Doses of Tafamidis

A PHASE 1, OPEN-LABEL, RANDOMIZED, CROSSOVER, SINGLE DOSE STUDY TO DETERMINE THE BIOEQUIVALENCE OF 12.2 MG TAFAMIDIS FREE ACID TABLET AND COMMERCIAL 20 MG TAFAMIDIS MEGLUMINE CAPSULE ADMINISTERED UNDER FASTED CONDITIONS TO HEALTHY PARTICIPANTS

Study to characterize the bioequivalence of a 12.2 mg free acid tablets compared to commercial supply (tafamidis meglumine soft gelatin 20 mg capsule) in healthy participants under fasted conditions.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • New Haven Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female participants must be 18 to 55 years of age, inclusive, at the time of signing the ICD.
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, laboratory tests, and cardiovascular tests.
3. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.
4. BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
5. Capable of giving signed informed consent and compliance with study requirements and restrictions

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).
2. Any condition possibly affecting drug absorption (eg, gastrectomy).
3. History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, HBcAb, or HCVAb. Hepatitis B vaccination is allowed.

4. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.

   Prior/Concomitant Therapy:

5. 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.

   Prior/Concurrent Clinical Study Experience:

6. Previous administration with an investigational drug 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:

7. A positive urine drug test.
8. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine 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.
9. Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, baseline QTc interval >450 msec, 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 baseline uncorrected QT interval is >450 msec, this interval should be rate corrected using the Fridericia method and the resulting QTcF should be used for decision making and reporting. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc or QRS values should be used to determine the participant's eligibility. Computer interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding participants.

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:

    • AST or ALT level greater than or equal to 1.5 × upper limit of normal (ULN);
    • Total bilirubin level greater than or equal 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 greater than or equal ULN.

    Other Exclusions:

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. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
13. History of sensitivity to heparin or heparin induced thrombocytopenia.
14. Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.
15. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
16. 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
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Tafamidis Free acid tablet then tafamidis meglumine capsule; On Day 1 of each period, participants will receive a single dose of 1 of tafamidis formulations. Each period is separated by a washout of at least 16 days between administration of study drug.	Drug: Tafamidis free acid tablet; 12.2 mg tafamidis free acid tablet; Drug: Tafamidis meglumine capsule; 20 mg tafamidis meglumine soft gelatin capsule
EXPERIMENTAL: Tafamidis meglumine capsule then Tafamidis Free acid tablet; On Day 1 of each period, participants will receive a single dose of 1 of tafamidis formulations. Each period is separated by a washout of at least 16 days between administration of study drug.	Drug: Tafamidis free acid tablet; 12.2 mg tafamidis free acid tablet; Drug: Tafamidis meglumine capsule; 20 mg tafamidis meglumine soft gelatin capsule

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration-time curve (AUC72)	Area under the plasma concentration-time profile from time 0 to 72 hours post-dose	Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72
Area under the plasma concentration-time curve (AUClast)	Area under the plasma concentration time profile from time zero to the time of the last quantifiable concentration	Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168
Time to Reach Maximum Observed Plasma Concentration (Tmax)	Time to Reach Maximum Observed Plasma Concentration (Tmax)	Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168
Mean residence time (MRT)	Mean residence time (MRT)	Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168
Plasma Decay Half-Life (t1/2)	Plasma Decay Half-Life (t1/2)	Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168
Number or percentage of patients with abnormal physical examination findings	Assessment of abnormal physical examination findings during study participation	Baseline up to Day 25
Number or percentage of patients with change from baseline in Clinical Laboratory parameters	Change in clinical laboratory parameters	Baseline up to Day 25
Number or percentage of patients with change from baseline in Vital sign measurements	Change in vital sign measurements	Baseline up to Day 25
Number of patients with change in ECG parameters	Change in ECG parameters	Baseline up to Day 25
Incidence of adverse events	Assessment of adverse events during study participation and up to 28 days after last dose	Baseline up to Day 46

Collaborators and Investigators

• Sponsor: 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 17, 2020
• Primary Completion (ACTUAL): February 23, 2021
• Study Completion (ACTUAL): February 23, 2021

Study Registration Dates

• First Submitted: September 23, 2020
• First Submitted That Met QC Criteria: September 29, 2020
• First Posted (ACTUAL): October 5, 2020

Study Record Updates

• Last Update Posted (ACTUAL): March 8, 2021
• Last Update Submitted That Met QC Criteria: March 4, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: B3461095; Tafamidis (OTHER: Alias Study Number)

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