Supplement to: Medication Development for the Treatment of Alcohol Use Disorder - U01AA028957

点击翻译按钮获取中文摘要

Nearly 15 million people in the US and ~100 million worldwide suffer from AUD. Over 5% of all medical morbidities share an ethanol-related risk. Although there are three FDA approved drugs to treat AUD, and several others are used off-label, medications have shown only modest success (in ~20% of patients treated). As a consequence, there is an urgent need for new pharmacotherapeutics across the DSM-V AUD spectrum. Our approach in U01AA028957 was a straightforward medchem plan, IND-enabling studies followed by first in human safety tests. A supplement is requested to meet unexpected direct expenses for Original Aim 1 and 2 with benefit to aims 3-4. [Original Aims: 1: Development of manufacturing standards; 2: Completion of pre-clinical IND enabling studies; 3: Phase I clinical trial; single- ascending dose; 4: Phase I clinical trial; multiple-ascending dose.] Specifically, based on estimations from Charles Rivers Lab and our consultants, we had anticipated needing 1 kg of compound to complete the animal studies of aim 2. As such, the purification method we developed would have sufficed. However, we now need to significantly upscale production. Curia Global is a company that produces metric tons of minocycline and has competitively bid to complete the GMP drug needs for this grant. However, we need them to eliminate a purification step, which, if successful, will dramatically reduce the future costs of the higher need. Given their experience with tetracycline and in further discussions with them, they are confident they can remove the problematic chromatographic purification step during tech transfer. The dividend for Aims 3 and 4 will be that the commensurate costs will be ~$16,000 rather than ~$60,000 per kg. These costs were not covered in the original proposal. The goal of the supplement is: To improve efficiency and increase output from 1 to approximately 15 kg butylether minocycline in support of both pre-IND and phase 1 activities.