Pharmacokinetics of DFN-15, a Novel Oral Solution of Celecoxib, Versus Celecoxib 400-mg Capsules: A Randomized Crossover Study in Fasting Healthy Volunteers

Abstract

Background: COX-2 inhibitors can be effective for acute migraine, but none is supplied in a rapidly absorbed, ready-to-use oral liquid formulation. DFN-15, a novel oral liquid formulation of celecoxib, is being developed for the acute treatment of migraine with or without aura. Clinical studies with this formulation are ongoing.

Objectives: The objectives of the present study were to compare the bioavailability of DFN-15 with that of the commercial formulation of celecoxib 400-mg oral capsules (Celebrex®) and to determine the dose proportionality of DFN-15 in healthy fasted volunteers.

Methods: This single-dose randomized crossover study in 16 healthy fasted volunteers evaluated the pharmacokinetics and relative bioavailability of DFN-15 at doses of 120, 180, and 240 mg against the commercial formulation of celecoxib 400-mg oral capsules and determined the dose proportionality of DFN-15.

Results: The maximum observed plasma concentrations (C max) of celecoxib after the administration of DFN-15 120, 180, and 240 mg (1062-1933 ng/ml) were higher than for the 400-mg oral capsules (611 ng/ml). The median time to peak concentration (T max) was within 1 h for DFN-15 and 2.5 h for the oral capsules. The pharmacokinetics of DFN-15 were dose proportional from 120 to 240 mg. Partial area under the plasma concentration-time curves (AUCs) from 15 min to 2 h for DFN-15 120 mg were at least threefold higher than for the oral capsules, and the relative bioavailability of DFN-15 was approximately 140% that of the oral capsules. DFN-15 was well tolerated, with no new or unexpected adverse events.

Conclusions: Based on a faster rate of absorption and increased bioavailability, DFN-15 is being evaluated as an abortive medication for acute treatment in patients with migraine.

Conflict of interest statement

Funding

This study was sponsored by Dr. Reddy’s Laboratories Ltd., which developed DFN-15.

Conflict of interest

AP, SS, AG, and SM are employees of Dr. Reddy’s Laboratories, developer of DFN-15; JN, MG, and JG were paid consultants of Dr. Reddy’s Laboratories.

Ethical approval

This study was conducted in compliance with the ethical principles of the Declaration of Helsinki (7th revision, 2013), the International Council for Harmonisation Guideline E6 for Good Clinical Practice, and the US FDA Code of Federal Regulations Title 21 (part 56). The protocol and the informed consent form were reviewed and approved by Quorum Review IRB (Seattle, WA, USA).

Informed consent

All subjects voluntarily participated in this study. They signed an informed consent form, which explained the nature and objectives of the study as well as any known side effects and/or adverse reactions associated with study medications, after having fully comprehended its contents.

Figures

Fig. 1

Mean plasma concentration-time profile of DFN-15 and celecoxib oral capsules through 72 h post-dose on a semi-logarithmic scale, with an inset showing the same measurements through 3 h post-dose. Note at each time point post-dose, individual plasma concentrations were averaged to obtain mean concentrations. Averaging of individual concentrations from five subjects (all concentrations are above the limit of quantitation) on DFN-15 180 mg at 5 min post-dose resulted in a value of 5.8 ng/ml