Low dose topiramate/phentermine composition and methods of use thereof
Inventors
Najarian, Thomas • Tam, Peter Y. • Wilson, Leland F.
Assignees
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Publication Number
US-8895058-B2
Publication Date
2014-11-25
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 low-dose oral weight-loss therapy combining an immediate-release phentermine formulation with a controlled release topiramate formulation. It addresses weight loss in patients having a body mass index (BMI) of at least 25 kg/m2 by providing a unit dosage form for oral administration. The phentermine unit dosage is specified in the range of 2 mg to 8 mg and is paired with a topiramate unit dosage in the range of 15 mg to 50 mg.
A central aspect is the pharmacokinetic behavior of the controlled release topiramate formulation. After oral administration, the controlled release topiramate formulation reaches a maximum plasma concentration (Cmax) at about 6 to about 10 hours (Tmax) and exhibits a lower Cmax than non-controlled release topiramate. The lower Cmax is achieved without decreasing total drug exposure, defined by the area under the concentration-time curve (AUC).
The invention also describes unit-dose forms and packaged pharmaceutical preparations for the oral regimen, including encapsulation into capsules and packaging such as blister packs. Exemplary regimens include 3.75 mg phentermine with 23 mg topiramate and 7.5 mg phentermine with 46 mg topiramate. The controlled release topiramate formulation is described in terms of a controlled-release bead composition and coatings, and the immediate-release phentermine formulation is described as an immediate-release bead formulation, with both formulations incorporated into the unit dosage form.
Claims Coverage
The document includes at least one independent claim, which defines a unit dosage form for oral weight loss with a specific phentermine-to-topiramate dosing ratio and specific controlled-release topiramate pharmacokinetic properties. The inventive feature set in the independent claim includes formulation composition ranges, a dosing ratio, and pharmacokinetic requirements (Tmax, lower Cmax, and maintained AUC).
Unit dosage oral weight-loss formulation with immediate-release phentermine and controlled-release topiramate
A unit dosage form for oral administration to a patient having a body mass index of at least 25 kg/m2, comprising a combination of an immediate release phentermine formulation containing a unit dosage of phentermine in the range of 2 mg to 8 mg and a controlled release topiramate formulation containing a unit dosage of topiramate in the range of 15 mg to 50 mg.
Phentermine-to-topiramate mg/day ratio
The dosage of phentermine in mg/day is about 16% of the dosage of topiramate in mg/day.
Controlled-release topiramate pharmacokinetics with delayed Tmax and reduced Cmax without decreased AUC
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, without decreasing total drug exposure defined by the area under the concentration-time curve (AUC).
The independent claim coverage centers on an oral unit dosage weight-loss formulation for BMI ≥ 25 kg/m2 that combines immediate-release phentermine (2–8 mg) with controlled-release topiramate (15–50 mg) using an approximately 16% phentermine-to-topiramate mg/day ratio, while achieving delayed Tmax (about 6–10 hours) and a lower Cmax than non-controlled release topiramate without decreasing AUC.
Stated Advantages
Controlled release topiramate exhibits a lower Cmax than non-controlled release topiramate.
Lower Cmax is achieved without decreasing total drug exposure defined by AUC.
Documented Applications
Oral weight loss therapy for patients having a body mass index of at least 25 kg/m2.
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