Healthy
Conditions
Keywords
tafamidis
Brief summary
The purpose of this clinical trial is to compare the amount of tafamidis in blood after taking two different tablet forms of tafamidis This study is seeking healthy participants over the age of 18. All participants in the study will receive one tablet of study medicine on the first day, then receive one dose of the other tablet form 16 days later. We will compare the amounts in blood for 8 days after taking each dose of the study medicine. Participants will take part in this study for about 80 days. The first visit is a screening visit to ensure that participants are appropriate for the study. Up to 28 days later, they will visit the study clinic twice (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.
Interventions
Variant 12.2 mg tafamidis free acid tablet (Test)
DRUGTafamidis free acid tablet (Reference)
Proposed commercial 12.2 mg tafamidis free acid tablet (Reference)
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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. Body Mass Index 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 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. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Tafamidis (Both Variant 12.2 mg Tafamidis Free Acid Tablet and Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet) | Days 1 (Pre-dose,0.5,1,2,3,4,6,8,12 hours post dose),2,3,4,5,6,7 and 8 in both Periods 1 and 2. | The AUCinf was determined by AUClast+ (Clast\*/kel), where Clast\* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis; kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. |
| Maximum Plasma Concentration (Cmax) of Tafamidis (Both Variant 12.2 mg Tafamidis Free Acid Tablet and Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet) | Days 1 (Pre-dose,0.5,1,2,3,4,6,8,12 hours post dose),2,3,4,5,6,7 and 8 in both Periods 1 and 2. | Cmax was observed directly from data. |
Countries
Belgium
Participant flow
Pre-assignment details
This is a 2-period,fixed-sequence crossover study. A total of 12 participants were randomized and assigned to study treatments.
Participants by arm
| Arm | Count |
|---|---|
| Variant 12.2 mg Tafamidis Free Acid Tablet->Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet Participants received 1 dose of Variant 12.2 mg Tafamidis free acid tablet on Day 1 of Period 1, then after a washout of at least 16 days, participants received 1 dose of Proposed commercial 12.2 mg tafamidis free acid tablet. | 6 |
| Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet->Variant 12.2 mg Tafamidis Free Acid Tablet Participants received 1 dose of Proposed commercial 12.2 mg tafamidis free acid tablet on Day 1 of Period 1 ,then after a washout of at least 16 days, participants received 1 dose of Variant 12.2 mg Tafamidis free acid tablet. | 6 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | No longer meets eligibility criteria | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Variant 12.2 mg Tafamidis Free Acid Tablet->Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet | Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet->Variant 12.2 mg Tafamidis Free Acid Tablet | Total |
|---|---|---|---|
| Age, Customized 18-44 years | 4 Participants | 3 Participants | 7 Participants |
| Age, Customized < 18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 45-64 yerars | 2 Participants | 3 Participants | 5 Participants |
| Age, Customized >= 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race White | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 12 |
| other Total, other adverse events | 6 / 11 | 4 / 12 |
| serious Total, serious adverse events | 0 / 11 | 0 / 12 |
Outcome results
Primary
Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Tafamidis (Both Variant 12.2 mg Tafamidis Free Acid Tablet and Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet)
The AUCinf was determined by AUClast+ (Clast\*/kel), where Clast\* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis; kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time frame: Days 1 (Pre-dose,0.5,1,2,3,4,6,8,12 hours post dose),2,3,4,5,6,7 and 8 in both Periods 1 and 2.
Population: The PK parameter population was defined as all participants who received at least 1 dose of tafamidis and who had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Variant 12.2 mg Tafamidis Free Acid Tablet (Test) | Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Tafamidis (Both Variant 12.2 mg Tafamidis Free Acid Tablet and Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet) | 58630 hour(h)*ng/mL | Geometric Coefficient of Variation 21 |
| Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet (Reference) | Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Tafamidis (Both Variant 12.2 mg Tafamidis Free Acid Tablet and Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet) | 57060 hour(h)*ng/mL | Geometric Coefficient of Variation 25 |
90% CI: [92.92, 104.1]Mixed effect model
Primary
Maximum Plasma Concentration (Cmax) of Tafamidis (Both Variant 12.2 mg Tafamidis Free Acid Tablet and Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet)
Cmax was observed directly from data.
Time frame: Days 1 (Pre-dose,0.5,1,2,3,4,6,8,12 hours post dose),2,3,4,5,6,7 and 8 in both Periods 1 and 2.
Population: The PK concentration population was defined as all participants who receive dat least 1 dose of tafamidis and who had at least 1 measurable concentration of tafamidis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Variant 12.2 mg Tafamidis Free Acid Tablet (Test) | Maximum Plasma Concentration (Cmax) of Tafamidis (Both Variant 12.2 mg Tafamidis Free Acid Tablet and Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet) | 875.2 ng/mL | Geometric Coefficient of Variation 22 |
| Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet (Reference) | Maximum Plasma Concentration (Cmax) of Tafamidis (Both Variant 12.2 mg Tafamidis Free Acid Tablet and Proposed Commercial 12.2 mg Tafamidis Free Acid Tablet) | 926.5 ng/mL | Geometric Coefficient of Variation 22 |
90% CI: [81.5, 102.9]Mixed effect model