Abstract

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A pivotal biostudy comparing ritonavir 100 mg film-coated tablet to a ritonavir 100 mg soft gelatin capsule in healthy adult subjects

Presented by Barry Bernstein, United States.

C. Klein¹, Y.-L. Chiu¹, W. Awni¹, W.-K. Ng¹, J. Xiong¹, W. Roth², T. Podsadecki¹, D. Kim¹, B. Bernstein¹

¹Abbott Laboratories, Abbott Park, United States, ²Abbott GmbH, Ludwigshafen, Germany

Background: A new 100 mg tablet formulation of ritonavir is being developed that would not require refrigeration. A pilot study of a prototype tablet showed that the area under the curve (AUC) after administration of the tablet was bioequivalent to the marketed soft-gelatin capsule (SGC). Additional refinements improved physical stability of the tablet formulation. This pivotal study compared the single-dose bioavailability of a final ritonavir 100 mg tablet formulation relative to the ritonavir 100 mg SGC under a moderate-fat meal condition.
Methods: This was a single-dose, open-label, 2-period crossover study with a group sequential (2 stage) design. Healthy male and female subjects (N = 93) participated in Stage 1 of the study. Serial blood samples were collected for 36 hours after each dose. Ritonavir AUC and maximum plasma concentration (Cmax) were determined. The bioavailability of the tablet formulation relative to SGC was assessed by the two one-sided tests procedure using 92.8% confidence intervals (CI). If bioequivalence was not declared following Stage 1 and the lower bounds of the CI for Cmax or AUC were not above 1.118, Stage 2 would enroll 60 subjects. Safety was assessed throughout the study.
Results:

	Parameter	Central Value		Point Estimate	92.8% Confidence Interval
		Tablet	SGC
	Cmax(mcg/ml)	0.37	0.29	1.264	1.150 - 1.389
Tablet vs. SGC	AUCt (mcg*h/ml)	3.15	2.78	1.134	1.068 - 1.205
	Aucinf (mcg*h/ml)	3.25	2.95	1.103	1.040 - 1.170

The study met its pre defined stopping criteria after Stage 1. Ritonavir AUC met bioequivalence criteria; the Cmax was approximately 26% higher with the tablet formulation. Both formulations were generally safe and well tolerated.
Conclusions: Ritonavir AUC for the new tablet was bioequivalent to the marketed SGC. The increase in ritonavir Cmax of 26% was slightly less than that observed with the marketed lopinavir/ritonavir tablet formulation.

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