Clinical trial NCT04575116: A Study to Determine the Bioequivalence of Two Doses of Tafamidis
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2020-10-05
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Area under the concentration-time curve (AUCinf)
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168
Secondary outcomes:
measure: Area under the plasma concentration-time curve (AUC72)
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72
measure: Area under the plasma concentration-time curve (AUClast)
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168
measure: Mean residence time (MRT)
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168
measure: Plasma Decay Half-Life (t1/2)
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168
measure: Number or percentage of patients with abnormal physical examination findings
timeFrame: Baseline up to Day 25
measure: Number or percentage of patients with change from baseline in Clinical Laboratory parameters
timeFrame: Baseline up to Day 25
measure: Number or percentage of patients with change from baseline in Vital sign measurements
timeFrame: Baseline up to Day 25
measure: Number of patients with change in ECG parameters
timeFrame: Baseline up to Day 25
measure: Incidence of adverse events
timeFrame: Baseline up to Day 46
Other outcomes:
Locations:
city: New Haven
country: United States
facility: New Haven Clinical Research Unit
state: Connecticut
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: