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

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

Additional Analysis > Bioequivalence of Vyndaqel / Vyndamax > PK Data

Ratios of adjusted geometric means (90% CI)
(Free acid 61 mg to meglumine 4 x 20 mg)

AUC: 102% (CI: 98-107)

C_max: 94% (CI: 89-99)

The two formulations are not
interchangeable on a per mg Basis

Mean (±SE)
plasma tafamidis concentration (ng/mL)

Nominal time post-dose (hours)

Tafamidis 61 mg free acid capsules

Tafamidis meglumine 4 Χ 20 mg capsules

4000

5000

6000

7000

8000

9000

10000

AUC: area under the curve; CI: confidence interval; C_max: maximum serum concentration; SE: standard error.

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

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

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

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

Dosage and Administration5,9

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

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

Dosage and Administration^5,9