A Study to Determine the Bioequivalence of Two Doses of Tafamidis

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Tafamidis free acid tablet; Drug: Tafamidis meglumine capsule

• Registration Number: NCT04575116
• Lead Sponsor: Pfizer

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-09-17
• Study First Submitted: 2020-09-23
• Study First Submitted QC: 2020-09-29
• Study First Posted: 2020-10-05
• Primary Completion: 2021-02-23
• Study Completion: 2021-02-23
• Status Verified: 2021-03
• Last Update Submitted: 2021-03-04
• Last Update Posted: 2021-03-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Tafamidis meglumine capsule then Tafamidis Free acid tablet	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.
Tafamidis meglumine capsule then Tafamidis Free acid tablet	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.
Tafamidis Free acid tablet then tafamidis meglumine capsule	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.
Tafamidis Free acid tablet then tafamidis meglumine capsule	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

New Haven Clinical Research Unit; 🇺🇸 New Haven, Connecticut, United States