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Assessment of Bioequivalence between the Higher Strengths of Pirfenidone 400 mg and 600 mg with Equivalent Doses of Pirfenidone 200 mg

Hemant Joshi, Mukesh Kumar, Jaideep Gogtay, Meena Lopez, Milind Gole, Richa Sharma

Background: The standard of care for idiopathic pulmonary fibrosis is pirfenidone 200 mg tablets thrice daily (t.i.d, 600 mg/day) which is titrated to achieve the desired maintenance dose i.e 1800-2400 mg/day (600 mg-800 mg, t.i.d). However, this is associated with a high pill burden and can impact patient compliance. Therefore, two higher strengths (400 mg and 600 mg) of pirfenidone tablets have been developed which offer greater flexibility to facilitate tailored dosing and likely to improve patient compliance.

Methods: Two studies were conducted using an open-label, randomized, single-dose, two-treatment, two-period, twosequence, two-way crossover design in fed conditions with a washout period of 5-6 days between administration. In the first study, a single dose of 400 mg pirfenidone tablet was compared with 2 × 200 mg pirfenidone tablets and in the second study a single dose of 600 mg pirfenidone tablet was compared with 3 × 200 pirfenidone tablets. The assessment of bioequivalence between treatments in study 1: pirfenidone 1 × 400 mg vs. 2 × 200 mg tablets and study 2: pirfenidone 1 × 600 mg vs. 3 × 200 mg tablets was done by comparing the pharmacokinetic parameters: C_max, AUC_0-t and AUC_0-∞.

Results: 17 subjects were evaluated in the study with the lower strength (400 mg) and 43 subjects were evaluated in the study with the higher strength (600 mg). The ratios and 90% CI for the geometric mean in study 1 were 102.90% (89.33%-115.97%) for C_max, 104.61% (92.74%-116.58%) for AUC_0-t and 107.94% (95.75%-120.75%) for AUC_0-∞. The ratios and 90% CI for the geometric mean in study 2 were 97.96% (91.41%-104.99%) for C_max, 97.79% (93.96%-101.78%) for AUC_0-t and 97.88% (94.10%-101.81%) for AUC_0-∞. One adverse event was reported in study 1 and 4 adverse events in study 2. None of the adverse events were deemed to be serious AEs. All the treatments were well tolerated.

Conclusion: Single doses of pirfenidone 400 mg tablets when compared with pirfenidone 2 × 200 mg tablets and pirfenidone 600 mg tablets when compared with the 3 × 200 mg tablets met the bioequivalence criteria in terms of rate and extent of absorption under fed condition.