Pfizer - Safety & Tolerability in the Bioequivalence Study

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Safety & Tolerability in the Bioequivalence Study⁹

Additional Analysis > Bioequivalence of Vyndaqel / Vyndamax > Safety & Tolerability

The overall incidence of AEs was similar for the tafamidis 61 mg free acid (n=10, [33%]) and tafamidis meglumine 4 x 20 mg capsules (n=12, [40%])
The most common AE was headache after receiving either tafamidis regimen (reported by 5 participants)
No participant died during the study
No participant had serious treatment-related AEs or discontinued treatment due to AEs
No clinically relevant changes were observed in clinical laboratory parameters, vital signs, ECGs or physical examinations

AEs: adverse events; ECGs: electrocardiographs.

PK Data
Safety & Tolerability
Summary
Study Overview
Dosing

Study Overview
Study Design
Study Endpoints
Results
Conclusions and Summary
Additional Analysis
- Bioequivalence of VYNDAQEL/VYNDAMAX
- Long–term Analysis

PI
Reference
Reference
Reference

References:

Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2018;379(11):1007-1016.
Damy T, Garcia-Pavia P, Hanna M, et al. Efficacy and safety of tafamidis doses in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and long-term extension study. Eur J Heart Fail. 2021;23(2):277-285.
Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis treatment for patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2018;379(11):1007-1016. (Supplement).
Maurer MS, Elliott P, Merlini G, et al. Design and Rationale of the Phase 3 ATTR-ACT Clinical Trial (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial). Circ Heart Fail. 2017;10(6):e003815.
VYNDAQEL^® / VYNDAMAX^® Prescribing Information. New York, NY: Pfizer Inc. June 2021.
Data on file. Pfizer Inc, New York, NY.
Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2018;379(11):1007-1016. (Supplemental Figure S1).
Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis treatment for patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2018;379(11):1007-1016. (Supplement Table S5).
Lockwood PA, Le VH, O'Gorman MT, Patterson TA, et al. The Bioequivalence of Tafamidis 61-mg Free Acid Capsules and Tafamidis Meglumine 4 x 20-mg Capsules in Healthy Volunteers. Clin Pharmacol Drug Dev. 2020;9(7):849-854.
Elliott P, Drachman BM, Gottlieb SS, et al. Long-Term Survival With Tafamidis in Patients With Transthyretin Amyloid Cardiomyopathy. Circ Heart Fail. 2022;15(1):e008193.

Bioequivalence of Tafamidis 61-mg Free Acid Capsules and Tafamidis Meglumine 4 × 20-mg Capsules in Healthy Volunteers⁹

Open-label, randomized, 2-period, 2-sequence, crossover, multiple-dose bioequivalence study in normal volunteers comparing 61 mg tafamidis free acid capsules to 4 x 20 mg tafamidis meglumine capsules
Designed to meet prespecified standard FDA bioequivalence criteria of (90% CI, 80%-125%)

Screening

Randomization

15 patients

7 days

Tafamidis 61 mg free
acid capsules

7 days

Tafamidis meglumine
4 x 20 mg capsules

16 days
washout

Tafamidis meglumine
4 x 20 mg capsules

7 days

16 days
washout

Tafamidis 61 mg free
acid capsules

7 days

Dosage and Administration^5,9

VYNDAQEL 80 mg (four 20-mg tafamidis meglumine capsules) orally once daily

VYNDAMAX 61 mg (one 61-mg tafamidis capsule) orally once daily

VYNDAMAX 61 mg capsule is bioequivalent¹ at steady-state to VYNDAQEL 80 mg (4 x 20 mg soft gelatin capsules) Not substitutable on a per-mg Basis.

¹As determined by the predefined 90% Confidence Interval criteria of 80–125% bioequivalence tafamidis area under the curve (AUC) and peak plasma concentration (C_max) after repeated oral daily dosing for 7 days.

The capsules should be swallowed whole and not crushed or cut
If a dose is missed, instruct patients to take the dose as soon as remembered or to skip the missed dose and take the next dose at the regularly scheduled time. Do not double the dose

VYNDAQEL (tafamidis meglumine)
Molecular Weight: 503.33 g/mol

VYNDAMAX (tafamidis)
Molecular Weight: 308.12 g/mol

Safety & Tolerability in the Bioequivalence Study9

Bioequivalence of Tafamidis 61-mg Free Acid Capsules and Tafamidis Meglumine 4 × 20-mg Capsules in Healthy Volunteers9

Dosage and Administration5,9

Safety & Tolerability in the Bioequivalence Study⁹

Bioequivalence of Tafamidis 61-mg Free Acid Capsules and Tafamidis Meglumine 4 × 20-mg Capsules in Healthy Volunteers⁹

Dosage and Administration^5,9