Synthonics, Inc. — Department of Health and Human Services SBIR Phase II: 200

Description

ABSTRACT This proposal addresses the clinical deficiency of the currently available oral treatments for hypothyroidism. Whereas levothyroxine (LT4, Synthroid® and other products) is the standard of care and effectively resolves symptoms in most patients, some hypothyroid patients are commonly treated with a combination of LT4 and liothyronine (LT3, Cytomel® and other products). LT3 has the disadvantage of being absorbed too rapidly, too short-lived and associated with potential side-effects to act as an effective complement to T4. If the value of combining T3 with T4 is to be ultimately realized for these patients, a controlled release product that delivers T3 in a fashion that produces physiologically normal (euthyroid) plasma levels will be needed. Euthyroid plasma T3 levels are important to achieve normal thyroid hormone concentrations in all tissues. The broad, long- term objective of this product is to provide patients a new thyroid hormone drug product that produces euthyroid-like T3 levels with once daily oral dosing. The metallo-T3 complexes are designed to be insoluble. They slowly pass through and settle in the gastrointestinal tract where T3 molecules gradually break free from the metal complex and enter the blood stream. This modulates the rate of delivery and thereby the rate of T3 drug absorption.Project Narrative Optimal treatment with thyroid hormones in hypothyroid patients is a significant issue with respect to public health. Although controversial in the past, the addition of liothyronine (T3) to levothyroxine (T4) to treat patients that are sub-optimally treated with T4 alone has gained acceptance. This project is focused on the development of a sustained-release oral dosage form of T3 with a target product profile that includes producing normal T3 serum levels thus addressing the clinical deficiency associated with the currently marketed immediate release form of T3.