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IN-VIVO METHOD FOR DETERMINING BIOEQUIVALENCE OF SEVELAMER COMPOSITIONS

IP.com Disclosure Number: IPCOM000238673D
Publication Date: 2014-Sep-10
Document File: 7 page(s) / 122K

Publishing Venue

The IP.com Prior Art Database

Abstract

The present disclosure relates to an in-vivo method of determining bioequivalence between a reference sevelamer composition and a generic sevelamer composition. The method comprises determining the phosphate binding capacity of the reference sevelamer composition and the generic sevelamer composition by measuring the amount of phosphorous in the rectal effluent of healthy volunteers after administering the respective sevelamer compositions.

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IN-VIVO METHOD FOR DETERMINING BIOEQUIVALENCE OF SEVELAMER COMPOSITIONS

Abstract

The present disclosure relates to an in-vivo method of determining bioequivalence between a reference sevelamer composition and a generic sevelamer composition.  The method comprises determining the phosphate binding capacity of the reference sevelamer composition and the generic sevelamer composition by measuring the amount of phosphorous in the rectal effluent of healthy volunteers after administering the respective sevelamer compositions.

Reported herein is an in-vivo method of determining bioequivalence between a reference sevelamer composition and a generic sevelamer composition, the method comprises:

a)   determining the phosphate binding capacity of both the reference sevelamer composition and the generic sevelamer composition by measuring the amount of phosphorous in the rectal effluent of healthy volunteers after administering the respective sevelamer compositions; and

b)   comparing the phosphate binding capacity of the reference sevelamer composition and the generic sevelamer composition;

wherein the equivalent phosphate binding capacity of the reference sevelamer composition and the generic sevelamer composition indicates bioequivalence between the two compositions.

“Reference sevelamer composition”, as used herein, refers to the reference drug product.  The reference drug product is the reference listed drug product to which the in-vivo bioequivalence and, in some instances, the in-vitro bioequivalence of the generic applicant’s product is compared.  Renvela® (sevelamer carbonate tablets, 800 mg) acts as the reference drug product in the present disclosure.

“Generic sevelamer composition”, as used herein, refers to the test drug product.  The test drug product is the generic applicant’s product whose bioequivalence is to be established against the reference listed product.

“Sevelamer”, as used herein, includes sevelamer base and its pharmaceutically acceptable salts, e.g., carbonate, hydrochloride, and the like.

“Bioequivalence”, as used herein, refers to pharmacodynamic equivalence, i.e., absence of significant difference in pharmacodynamic end-point of sevelamer in the generic and the reference compositions.  Bioequivalence is said to have been achieved if 90% confidence limits on the least-squares geometric mean of generic/reference ratio of log transformed or untransformed phosphate binding capacity (PBC) are within the 80% to 125% interval.  PBC serves as the pharmacodynamic end-point.

“Phosphate binding capacity” (PBC), as used herein, refers to the ability of sevelamer to bind phosphorus.  Phosphorus includes phosphorus ions, phosphate, monohydrogen phosphate, dihydrogen phosphate, oxoacids of phosphorous, and the like.

wherein,

X = Phosphorus in rectal effluent following administration of a meal with a sevelamer composition (generic or reference)

Y = Phosphorus in rectal effluent following administration of a...