Low dose topiramate/phentermine composition and methods of use thereof
Inventors
NAJARIAN THOMAS, null • Najaraian, Thomas • Tam, Peter Y. • Wilson, Leland F.
Assignees
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Publication Number
US-8580298-B2
Publication Date
2013-11-12
Expiration Date
Abstract
A method for effecting weight loss by administering a combination of topiramate and phentermine is provided. The phentermine is generally administered in immediate release form, in a daily dose in the range of 2 mg to 8 mg, in combination with a daily dose of topiramate selected to prevent the loss of effectiveness of phentermine alone. Methods for treating obesity, conditions associated with obesity, and other indications are also provided, as are compositions and dosage forms containing low doses of phentermine and topiramate, e.g., 3.75 mg phentermine and 23 mg topiramate.
Core Innovation
The invention relates to a unit dosage form for weight loss for oral administration to a patient having a body mass index of at least 30 kg/m2 and a condition associated with obesity. The unit dosage form comprises a combination of an immediate release phentermine formulation with a unit dosage of phentermine in the range of 2 mg to 8 mg, and a controlled release topiramate formulation with a unit dosage of topiramate in the range of 15 mg to 50 mg. The phentermine dosage in mg/day is about 16% of the topiramate dosage in mg/day.
The controlled release topiramate formulation reaches a maximum plasma concentration (Cmax) at about 6 to about 10 hours (Tmax) after administration and exhibits a lower Cmax than non-controlled release topiramate. The controlled release topiramate formulation does not decrease total drug exposure defined by the area under the concentration-time curve (AUC), and this combination enables reduction of concentration-dependent side effects without a decrease in efficacy.
In certain embodiments, the controlled release topiramate formulation comprises controlled release beads of the topiramate, a binder, and a polymeric filler in a matrix core, where the matrix core is provided with a delayed release coating comprising ethyl cellulose and polyvinyl pyrrolidone. The invention also describes packaged pharmaceutical preparations that comprise multiple unit dosage forms in sealed containers and instructions for administering the dosage forms orally to effect weight loss.
Claims Coverage
Two independent claims are provided. They cover a unit oral weight-loss dosage form with specified phentermine/topiramate dosing proportions and controlled-release topiramate pharmacokinetics, and a unit dosage form that further specifies the controlled-release topiramate bead/matrix core with delayed release coating composition.
Phentermine immediate-release plus controlled-release topiramate weight-loss unit dosage form with matched dosing proportion
A unit dosage form for weight loss for oral administration to a patient with body mass index of at least 30 kg/m2 and a condition associated with obesity, comprising an immediate release phentermine formulation (2 mg to 8 mg) and a controlled release topiramate formulation (15 mg to 50 mg), wherein the phentermine dosage in mg/day is about 16% of the topiramate dosage in mg/day.
Controlled-release topiramate pharmacokinetic profile without AUC decrease to reduce concentration-dependent side effects
The controlled release topiramate formulation reaches Cmax at about 6 to about 10 hours (Tmax) after administration, exhibits a lower Cmax than non-controlled release topiramate, and without decreasing total drug exposure defined by AUC, thereby enabling reduction of concentration-dependent side effects without a decrease in efficacy.
Controlled-release topiramate bead/matrix core delayed coating formulation
A unit dosage form in which the controlled release topiramate formulation comprises controlled release beads of the topiramate, a binder, and a polymeric filler in a matrix core, where the matrix core is provided with a delayed release coating comprising ethyl cellulose and polyvinyl pyrrolidone.
Across the independent claims, the coverage centers on combining immediate release phentermine with controlled release topiramate in a specified dosing proportion, using controlled-release topiramate pharmacokinetics characterized by lower Cmax at about 6 to about 10 hours Tmax without decreasing AUC, and in one independent claim implementing a delayed release bead/matrix core with an ethyl cellulose and polyvinyl pyrrolidone coating.
Stated Advantages
Reduction of concentration-dependent side effects.
No decrease in efficacy despite reduced Cmax and maintained AUC.
Lower Cmax compared with non-controlled release topiramate while maintaining total drug exposure defined by AUC.
Documented Applications
Oral weight loss for a patient having a body mass index of at least 30 kg/m2 and a condition associated with obesity.
Packaged pharmaceutical preparation comprising multiple unit dosage forms in a sealed container with instructions for administering the dosage forms orally to effect weight loss.
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