A study to learn how different forms of study medicine tafamidis are taken up into the blood in healthy adults

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

15 Feb 2024 → 28 May 2024

Decision date (initial)

2024-02-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Pfizer Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others

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) in fasted healthy participants.

Conditions and MedDRA coding

aransthyretin amyloid cardiomyopathy

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-000884-PIP01-10

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

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 (BMI) of 16-32 kg/m2; and a total body weight >45 kg (99 lb).

Exclusion criteria 11

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 human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibody (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.
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).
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).
6. A positive urine drug test. A single repeat for positive drug screen may be allowed.
7. Screening supine blood pressure (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 electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, QTc corrected using Fridericia’s formula (QTcF) >450 ms, complete left bundle branch block (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 estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m². Based upon participant age at screening, eGFR is calculated using the recommended formulas to determine eligibility and to provide a baseline to quantify any subsequent kidney safety events.
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: - Alanine aminotransferase (ALT), aspartate aminotransferase (AST), Bilirubin ≥1.5 × upper limit of normal (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.
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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. AUCinf (if data permit, otherwise AUClast) and Cmax of tafamidis.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications